Licorice, the dried root or stolon of Glycyrrhiza glabra or G. ularensis, is commonly used worldwide as a food sweetener or crude drug. Its major ingredient is glycyrrhizin. Hypokalemia or pseudoaldosteronism (PsA) is one of the most frequent side effects of licorice intake. Glycyrrhizin metabolites inhibit type 2 11β-hydroxysteroid dehydrogenase (11βHSD2), which decomposes cortisol into inactive cortisone in the distal nephron, thereby inducing mineralocorticoid receptor activity. Among the several reported glycyrrhizin-metabolites, 18β-glycyrrhetyl-3-O-sulfate is the major compound found in humans after licorice consumption, followed by glycyrrhetinic acid. These metabolites are highly bound to albumin in blood circulation and are predominantly excreted into bile via multidrug resistance-associated protein 2 (Mrp2). High dosage and long-term use of licorice are constitutional risk factors for PsA. Orally administered glycyrrhizin is effectively hydrolyzed to glycyrrhetinic acid by the intestinal bacteria in constipated patients, which enhances the bioavailability of glycyrrhizin metabolites. Under hypoalbuminemic conditions, the unbound metabolite fractions can reach 11βHSD2 at the distal nephron. Hyper direct-bilirubin could be a surrogate marker of Mrp2 dysfunction, which results in metabolite accumulation. Older age is associated with reduced 11βHSD2 function, and several concomitant medications, such as diuretics, have been reported to affect the phenotype. This review summarizes several factors related to licorice-induced PsA, including daily dosage, long-term use, constipation, hypoalbuminemia, hyper direct-bilirubin, older age, and concomitant medications.

Kampo medicine has been the primary medical model in Japan until the mid 1800s, regained a prominent role in today's Japanese medical system. Today, 148 herbal Kampo formulas can be prescribed under the national health insurance system, allowing physicians to integrate Kampo in their daily practice. This article aims to provide information about the extent to which Kampo is now used in clinics throughout Japan and about physician's current attitudes toward Kampo. We used the results of a 2008 survey that was administered to physicians throughout Japan (n= 684). The data showed that 83.5% of physicians currently use Kampo in the clinic, although the distribution of physicians who use Kampo differ widely depending on the specialty and provided a breakdown of Kampo usage by specialty. It will be interesting to see how each specialty incorporates Kampo into its respective field as Kampo continues to play a pertinent role in Japanese medical system.

A cold sensation (hie) is common in Japanese women and is an important treatment target in Kampo medicine. Physicians diagnose patients as havinghiesho(cold disorder) whenhiedisturbs their daily activity. However, differences betweenhieandhieshoin men and women are not well described.Hiecan be of three types depending on body part where patients feelhie. We aimed to clarify the characteristics of patients withhieandhieshoby analyzing data from new patients seen at the Kampo Clinic at Keio University Hospital between 2008 and 2013. We collected information about patients’ subjective symptoms and their severity using visual analogue scales. Of 4,016 new patients, 2,344 complained abouthieand 524 of those were diagnosed withhiesho.Hiewas most common in legs/feet and combined with hands or lower back, rather than the whole body. Almost 30% of patients withhiefelt upper body heat symptoms like hot flushes. Cold sensation was stronger inhieshothannon-hieshopatients. Patients withhiehad more complaints. Men withhieshohad the same distribution ofhieand had symptoms similar to women. The results of our study may increase awareness ofhieshoand help doctors treathieand other symptoms.

Aim: We aimed to elucidate the present clinical situation, future challenges, and potential need for diagnostic support software in Kampo medicine.Methods: We conducted an online survey (comprising 28 questions) of Japanese physicians from the 23 to 24 January 2024 via MedPeer. The participants' responses were stratified according to their age distribution.Results: We evaluated data for 652 respondents. The most common respondent age groups were those in their 30s and 40s. The most common specialty of respondents was internal medicine (43.7%). Only 33.7% of respondents had received education on Kampo medicine at university. Most respondents (90.0%) were not licensed as certified physicians or members of the Japan Society for Oriental Medicine. Most respondents (86.7%) currently prescribed Kampo formulas (current users); only 3.8% had no experience in prescribing Kampo formulas. The conditions for which Kampo formulas were frequently prescribed were muscle cramps, constipation, medically unexplained symptoms/menopausal syndrome, appetite loss/malnutrition, and fatigue. However, 48.3% of current users did not use traditional Kampo patterns (sho). The most frequent issues reported by respondents were the lack of scientific evidence and standardization of diagnostic methods in Kampo medicine. Respondents indicated the need for postgraduate education and implementation of diagnostic support software for using Kampo patterns by non‐specialists in Kampo medicine.Conclusion: There was a discrepancy between the high frequency of Kampo formula prescriptions and the low use of traditional Kampo patterns in Japan. Diagnostic support software is likely to become a useful method of improving appropriate Kampo formula prescriptions by non‐specialists.

Objectives: We aimed to test our hypothesis that additional administration of traditional Japanese (Kampo) medicine, kakkonto (kakkon-to: KT) and shosaikotokakikyosekko (sho-saiko-to-ka-kikyo-sekko: SSKKS), is more effective in relieving symptoms and preventing the onset of severe infection in mild-to-moderate COVID-19 patients compared to those treated only with conventional treatment. Trial design: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator-sponsored, two-arm study. Participants: Patients and inpatients will be recruited from 8 Japanese academic and non-academic hospitals. The inclusion and exclusion criteria are as follows: Inclusion criteria: Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clinical stages of mild-to-moderate COVID-19 Symptomatic ≥ 20 years of age Male or female Ability to communicate in Japanese Outpatients and inpatients Provided informed consent Exclusion criteria: Difficulty in providing informed consent due to dementia, psychosis, or psychiatric symptoms Allergic to Kampo or Western medicines used in this study Pregnant and lactating Unable to follow up Participating in another clinical trial or interventional study Hypokalemic or taking oral furosemide or steroids Determined unsuitable for this study by the physician Intervention and comparator: Patients in the control group will receive conventional treatment with antipyretics, painkillers, or antitussives for symptoms that occurred after they contracted the SARS-CoV-2 infection. Patients in the Kampo group will receive 2.5 g of KT (TJ-1@TSUMURA and Co.) and 2.5 g of SSKKS (TJ-109@TSUMURA and Co.) 3 times a day, orally, for 14 days in addition to the conventional treatment as mentioned above. Main outcomes: The number of days till at least one of the symptoms (fever, cough, sputum, malaise, shortness of breath) improves in the first 14 days of treatment. To assess the cough, sputum, malaise, and shortness of breath, a numeric rating scale will be used to define improvement in terms of a 2-point decrease in the number of days from the start of treatment for at least 2 days. Fever will be defined as an improvement when the temperature is less than 37 °C. Randomization: Patients are randomized (1:1 ratio) to each group using the minimization method, with balancing of the arms with severity of disease stage and patient age (< 65, 65 to < 75, or ≥ 75 years). Computer-generated random numbers will be used for the minimization method. Blinding (masking): Open-label with no blinding Numbers to be randomized (sample size): The main research hypothesis of this study is that the combination of Kampo medicine and conventional treatment will significantly improve the patients’ symptoms (fever, fatigue, cough, sputum, and shortness of breath) during the first 14 days of treatment as compared with conventional treatment alone. Concerning the analysis of the primary endpoint, the duration of time before improvement of at least one of the common cold-like symptoms (fever, malaise, cough, sputum, and shortness of breath) will be estimated using the Kaplan-Meier method, and the survival curves will be compared between groups using the log-rank test. Assuming this method of analysis and based on previous studies reporting the efficacy of Kampo medicine for COVID-19 and H1N1 influenza patients, the median survival time in the Kampo medicine group is estimated as 3 days; this time will be 1.5 times longer in the control group. Assuming a one-sided significance level of 5%, a power of 70%, and an allocation ratio of 1:1, the required sample size is calculated as 126 cases. To compensate for a loss in follow-up, we plan to include 150 cases in both groups (Kampo group = 75, control group = 75). Trial status: Protocol version 1.2 as of August 20, 2020 Recruitment start (expected): October 1, 2020 Recruitment finish (expected): October 31, 2023 Trial registration: Japan Registry of Clinical Trials (jRCT) jRCTs021200020. Registered on August 25, 2020 Full protocol: The full protocol is attached as an additional file and is accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.