Hiroshi Yamada

Green tea (GT) catechins exhibit antiviral effects in experimental studies. However, we lack clinical evidence on the preventive effects of catechin concentrations in gargling against acute upper respiratory tract infections (URTIs). Therefore, we aimed to investigate the concentration-dependence of GT catechins in gargling on the incidence of URTIs. We conducted an open-label randomized study. The target population consisted of 209 students from the University of Shizuoka and Meiji University, who were randomly assigned to high-catechin (approximate catechin concentration: 76.4 mg/dL), low-catechin (approximate catechin concentration: 30.8 mg/dL), and a control water gargling (catechin concentration: 0 mg/dL) group. All participants gargled water or GT daily for 12 weeks. The symptoms of URTIs were recorded on a daily survey form by participants. The incidences of URTIs occurred in 6 (9.1%), 7 (10.8%), and 11 (15.7%) participants in the high-catechin, low-catechin, and water groups, respectively. Cox proportional hazards analysis, using background factors and prevention status as covariates, revealed a hazard ratio of 0.57 (95% Confidence Interval (CI): 0.21–1.55, p = 0.261) for the high-catechin vs. water group and 0.54 (95% CI: 0.20–1.50, p = 0.341) for the low-catechin vs. water group. Our findings showed the incidence of URTIs in a concentration-dependent GT gargling was not significantly different, partly owing to the low event rates caused by intense precautions against the coronavirus disease 2019 pandemic. Our study would serve as a foundation for the development of an advanced protocol with optimal concentrations and a larger number of participants.

Green tea components, such as catechins have been reported to provide several benefits including anti-oxidative, anti-viral/bacterial, and anti-inflammatory effects in vitro and in vivo. Catechins effectively inhibited the adsorption and replication of the influenza virus. Additionally, green tea contains theanine and vitamin C, which enhance the immunity against viral/bacterial infections. Based on these, green tea is hypothesized to have potential benefits in the prevention of influenza and other respiratory tract infections in the clinical setting. However, its specific effects in patients remain unclear. To determine the clinical significance of green tea in the prevention of respiratory tract infections, we conducted an observational study and eight interventional studies. Based on the results of three studies, consuming or gargling green tea or its components significantly aided in the prevention of influenza. Meanwhile, one study showed that green tea successfully prevented common colds. Catechin inhalation was also reported to decrease the bacterial load of methicillin-resistant Staphylococcus aureus in the sputum. Although the anti-viral/anti-bacterial effects of green tea components have been demonstrated in experimental studies, the clinical evidence remains limited. Further studies are required to confirm the clinical efficacy of green tea and its components in preventing respiratory tract infections.

Being in a prolonged depressed state increases the risk of developing depression. To investigate whether green tea intake is effective in improving depression-like moods, we used an experimental animal model of depression with lipopolysaccharide (LPS) and clarified the effects of green tea on the biological stress response and inflammation in the brain. Regarding the stress reduction effect of green tea, we found that the sum of caffeine (C) and epigallocatechin gallate (E) relative to the sum of theanine (T) and arginine (A), the major components of green tea, or the CE/TA ratio, is important. The results showed that depression-like behavior, adrenal hypertrophy as a typical stress response, and brain inflammation were suppressed in mice fed green tea components with CE/TA ratios of 2 to 8. In addition, the expression of Npas4, which is reduced in anxiety and depression, was maintained at the same level as controls in mice that consumed green tea with a CE/TA ratio of 4. In clinical human trials, the consumption of green tea with CE/TA ratios of 3.9 and 4.7 reduced susceptibility to subjective depression. These results suggest that the daily consumption of green tea with a CE/TA ratio of 4–5 is beneficial to improving depressed mood.

Green tea catechin ingestion or gargling exhibit anti-viral activity against upper respiratory infection. We hypothesized that retention in the oral cavity could improve the anti-viral effects of catechins. The present study investigated the oral retention of catechins in humans and the effect of catechin beverage viscosity on oral retention. Two intervention studies with different test beverages, beverage-C (40 mL, containing 73.4 mg of catechins) and beverage-XT (40 mL, beverage-C containing 100 mg xanthan gum) were conducted in 20 healthy volunteers (mean age 38.7 years). Catechin concentrations were measured in buccal mucosa samples collected at 10 min, 40 min, and 60 min after ingesting test beverages, and the catechin variability of the tissue after intake was compared between test beverages. As a result, the mean (SEM) concentrations of EGCG were 99.9 (27.2), 58.2 (16.6), and 22.3 (5.7) ng/mg-mucosa at 10, 40, and 60 min, respectively, after ingestion of beverage-XT. Similarly, the catechin concentrations were 86.1 (20.3), 32.2 (5.3), and 27.8 (5.9) ng/mg-mucosa after ingestion of beverage-C. The total retention volume over 60 min tended to be slightly higher after ingestion of beverage-XT, though the difference was not statistically significant. Additional studies are needed to confirm the effect of xanthan gum on improving oral retention of catechins.

The young leaves of green tea become lighter in color than usual when protected from sunlight by a shading net for about two weeks while growing. These leaves are called “shaded white leaf tea” or SWLT. In the eluate of SWLT, the amount of amino acids (361 mg/L) was significantly higher than that in regular tea (53.5 mg/L). Since theanine and arginine, the first and second most abundant amino acids in SWLT, have significant antistress effects, we examined the antistress effect of SWLT on humans. SWLT or placebo green tea (3 g) was eluted with room-temperature water (500 mL). Participants consumed the tea for one week prior to pharmacy practice and continued for 10 days in the practice period. The state-trait anxiety inventory, an anxiety questionnaire, tended to be scored lower in the SWLT group than the placebo, but other stress markers showed no differences. The effect of the difference in SWLT components examined with mice showed that aspartic acid and asparagine, which are abundant in SWLT, counteracted the antistress effects of theanine and arginine. Large amounts of caffeine also interfered with SWLT’s antistress effect. Thus, SWLT, which is high in caffeine and amino acids, suppressed depressant behavior in mice.

Catechins, phytochemicals contained mainly in green tea, exhibit antiviral activity against various acute infectious diseases experimentally. Clinical evidence supporting these effects, however, is not conclusive. We performed a placebo-controlled, single-blind, randomized control trial to evaluate the clinical effectiveness of consumption of catechins-containing beverage for preventing acute upper respiratory tract infections (URTIs). Two hundred and seventy healthcare workers were randomly allocated to high-catechin (three daily doses of 57 mg catechins and 100 mg xanthan gum), low-catechin (one daily dose of 57 mg catechins and 100 mg xanthan gum), or placebo (0 mg catechins and 100 mg xanthan gum) group. Subjects consumed a beverage with or without catechins for 12 weeks from December 2017 through February 2018. The primary endpoint was incidence of URTIs compared among groups using a time-to-event analysis. A total of 255 subjects were analyzed (placebo group n = 86, low-catechin group n = 85, high catechin group n = 84). The URTI incidence rate was 26.7% in the placebo group, 28.2% in the low-catechin group, and 13.1% in the high-catechin group (log rank test, p = 0.042). The hazard ratio (95% confidence interval (CI)) with reference to the placebo group was 1.09 (0.61–1.92) in the low-catechin group and 0.46 (0.23–0.95) in the high-catechin group. These findings suggest that catechins combined with xanthan gum protect against URTIs.

Theanine, a major amino acid in green tea, exhibits a stress-reducing effect in mice and humans. Matcha, which is essentially theanine-rich powdered green tea, is abundant in caffeine. Caffeine has a strong antagonistic effect against theanine. The stress-reducing effect of matcha was examined with an animal experiment and a clinical trial. The stress-reducing effect of matcha marketed in Japan and abroad was assessed based on its composition. The stress-reducing effect of matcha in mice was evaluated as suppressed adrenal hypertrophy using territorially-based loaded stress. High contents of theanine and arginine in matcha exhibited a high stress-reducing effect. However, an effective stress-reducing outcome was only possible when the molar ratio of caffeine and epigallocatechin gallate (EGCG) to theanine and arginine was less than two. Participants (n = 39) consumed test-matcha, which was expected to have a stress-reducing effect, or placebo-matcha, where no effect was expected. Anxiety, a reaction to stress, was significantly lower in the test-matcha group than in the placebo group. To predict mental function of each matcha, both the quantity of theanine and the ratios of caffeine, EGCG, and arginine against theanine need to be verified.

Recently, item responses and total scores on depression screening scales have been reported to have characteristic distributions in the general population. The distributional pattern of responses to the Patient Health Questionnaire-9 (PHQ-9) in the general population has not been well studied. Thus, we carried out a pattern analysis of the PHQ-9 item responses and total scores in US adults. Data (5372 individuals) were drawn from the 2013–2014 National Health and Nutrition Examination Survey in the United States. The item responses and total score distributions of the PHQ-9 data were investigated with graphical analysis and exponential regression model. Lines of item responses showed the same pattern among the nine items, characterized by crossing at a single point between “not at all” and “several days” and a parallel pattern from “several days” to “nearly every day” on a log-normal scale. The total score distribution of the PHQ-9 exhibited an exponential pattern, except for at the lower end of the distribution. The present results support that the item responses and total scores on the PHQ-9 in the general population show the same characteristic patterns, consistent with the previous studies using the Center for Epidemiologic Studies Depression Scale (CES-D) and Kessler Screening Scale for Psychological Distress (K6).

Total depressive symptom scores in the general population have been reported to follow an exponential distribution except at the lowest end of the range of scores. To verify the hypothesis that total depressive symptom scores follow the distribution of the latent trait, we performed a simulation study of depressive symptom scoring modeled after the Revised Clinical Interview Schedule (CIS-R). To simulate the scoring of ordinal scale items in CIS-R, two sets of random numbers were generated, one expressing the degree of the latent trait of depressive symptoms and another expressing the threshold for each item. Random latent trait numbers greater than those of item thresholds indicated the presence of specific symptoms. When exponential distribution was set to the latent trait’s random numbers and each item’s threshold had a certain degree of standard deviation, simulated total depressive symptom scores showed a linear pattern except at the lowest end of scores with a log-normal scale. Our results suggest that total depressive symptom scores follow the distribution of the latent trait of depressive symptoms due to the property of ordinal scales, which is characterized by individual differences in the threshold of each item.

The distributional pattern of total scores on depression screening scales in the general population has not been well studied. Recent studies suggest that the total scores on depression screening scales follow an exponential pattern, with the exception of the lower end of the distribution. To further investigate the findings, we determined the distributions of the total and individual item scores on the Kessler Screening Scale for Psychological Distress (K6). Data were obtained from the National Survey of Midlife Development in the United States. Participants comprised 6,223 individuals between the ages of 25 and 74. The distributions of the total and individual item scores in various combinations were investigated with histograms and regression analysis. Irrespective of the combination of items, the total and individual item scores followed an exponential pattern except at the lower scores. The estimated rate parameters of regression analysis were similar among distributions with the same number of chosen items. At the lower scores, the distributional patterns of total scores varied according to the ratio of “a little” to “none” for each item response. The present results have the potential to estimate the distribution of depressive symptoms in the general population. While the degree of depressive symptoms varies from individual to individual, an entire population may show a certain mathematical distribution.