[Improved Indophenol Titration Method for Ascorbic Acid Using a Dropper and Electronic Balance: Enhanced Convenience and Efficiency].

The analysis of ascorbic acid using the 2,6-dichloroindophenol (DCIP) titration method is a well-established technique, but requires the skilled handling of a burette for accurate measurements. In the present study, we propose a modified DCIP titrimetric method that replaces the burette with a dropper and employs an electronic balance to measure the titrated amount by weight. The dropper used can be flexibly selected, allowing for a wide range of drop sizes, from large to very small. This modification offers several advantages, including lower skill requirements, a 43% reduction in the analysis time, a 50% decrease in sample/reagent consumption, and the ability to prepare DCIP standard solutions tailored to the concentration of ascorbic acid in the sample being analyzed. Our analysis of several food samples using this improved method showed that inherent issues of the DCIP method, such as determining the titration end point, could not be resolved. Nevertheless, the improved titration method remains more convenient and adaptable than the original approach using a burette, enabling quick and accurate analysis, especially for unskilled analysts.

[Characteristics of Adverse events of Dietary Supplements Provided byMedical Professionals and their Application in Causality Evaluation Algorithm].

This study aimed to characterize the adverse events of dietary supplements provided by medical professionals and to examine whether there are challenges when applying each case to the causality evaluation algorithm. Data from 290 individual cases collected by the Tokyo Metropolitan Government in cooperation with the Tokyo Medical Association and Tokyo Pharmaceutical Association were analyzed. The causality evaluation algorithm that was used in this study was reported previously. Female patients accounted for 73% of those who experienced adverse events. Both male and female patients who had adverse events were in their 60s and 70s. Many of the participants had underlying diseases and aimed to improve their medical conditions. Furthermore, skin symptoms were the most common. Many of the supplements were made from natural substances, with an average of 7.7 ingredients in each product. More than half of the products were used for less than one month. In most cases, symptoms improved after discontinuation of the products or after the administration of medications. When each event was applied to the causality assessment algorithm, it was necessary to understand the information as follows: in cases of product discontinuation with simultaneous medications recovery was not concluding the product discontinuation, and the physician's judgement should be place as objective evidence. The algorithm was successfully applicable to cases provided by medical professionals and the evaluated results for all cases were 30% possible and 62% highly possible. The evaluated results indicate the relationship between products/ingredients and the symptom, and by adding information on the symptom and its severity, it is possible to clarify the phenomenon to be noted.

[Frequency of Worsening Clinical Test Values Related to Supplement Use: Estimation by Using Nationwide Online Survey].

This study examined the frequency of worsening clinical test values related to supplement use using a nationwide online survey, with a focus on liver function markers, and clarified the differences between outcome indices of diarrhea or skin manifestations. A nationwide online survey was conducted with 73,010 supplement users from the previous year. Of these, 221 individuals with worsening clinical test values responded to the full-scale survey. To compare surveys with different outcome indices, we used previously reported data from similar surveys.Only 0.5% of individuals who self-reported worsening of clinical test values caused by supplement use recognized an almost certain causal relationship. Among the test items, blood lipids were the most frequently reported. The frequency of worsening liver function markers was 0.2% in supplement users. Among those who experienced worsening clinical test values, 56.1% received no treatment and 82.4% did not report the incidence of worsening clinical test values anywhere. The ingredient-based classification of products revealed more "Peptides or animal by-products" and "Combination products/not classifiable products" than those associated with other categories. Compared to the results of the survey about the experience of diarrhea or skin manifestations, those who experienced worsening clinical test values were predominantly men, frequent and long-term users, and individuals whose products could not be identified.Few supplement users experience worsening of liver function markers, which does not seem serious. However, it is difficult for supplement users to recognize abnormal changes by themselves. Thus, it is important to record product information, usage, and changes in physical condition.

The Prevalence of Dietary Supplements That Claim Estrogen-like Effects in Japanese Women.

Recently, adverse events, such as irregular vaginal bleeding and menstrual disorders, associated with the use of dietary supplements containing Pueraria mirifica, have been reported in Japan. P. mirifica contains phytoestrogens, such as deoxymiroestrol and miroestrol. Therefore, we investigated the use of supplements that claim to have estrogen-like effects (i.e., estrogen-like supplements) in Japanese women aged from 15 to 69 years old in an online survey. The prevalence of estrogen-like supplement use was 5%, accounting for approximately 15% of the sample, including ex-users. The majority of the users were in their 40s and 50s, mainly using these supplements for the treatment of menopausal symptoms. In contrast, the younger generation mainly used them for beauty purposes, such as weight loss, mastogenic effects, and skin care. Many of them visited a clinic or took medicines for menstrual-related troubles. In all age groups, soybeans/isoflavones were the most commonly used, followed by equol and placenta. Participants in their teens and 20s also used P. mirifica. Among them, 16.2% had experienced adverse events, including irregular vaginal bleeding, breast swelling and pain, and heavy menstruation. In conclusion, estrogen-like supplement use is associated with adverse events; thus, it is necessary to pay attention to the use of these supplement. Furthermore, because the purpose of use differs depending on generation, caution according to each generation is necessary.

[Recognition and Prevalence of "Designated Ingredient, etc." in Health Foods].

From 2012 to 2017, many adverse events, such as irregular vaginal bleeding and menstrual disorders, associated with the use of health foods containing Pueraria mirifica were reported in PIO-NET. Health foods containing P. mirifica claim mastogenic or body shaping effects, and it is for this reason that many women use these products. As a result, the Japanese government investigated and assessed the possibility of the occurrence of adverse effects associated with the use of other ingredients in health foods and labelled P. mirifica, Coleus forskohlii, black cohosh, and greater celandine as "designated ingredient, etc."The present study showed that recognition of "designated ingredient, etc." was 45.9% and that there was a difference between consumers and healthcare professionals. The prevalence of food containing P. mirifica use was 1.2%. Almost half of users experienced adverse events, such as irregular vaginal bleeding and menstrual disorder. Some subjects had a good perception towards "designated ingredient, etc.," such as "It seems effective"(32.7%) and "It seems good for health"(18.9%). After reading the descriptive text, their positive perceptions decreased.In conclusion, the recognition of "designated ingredient, etc." is insufficient. To avoid adverse events associated with "food containing designated ingredient, etc.," detailed information should be provided.

Coleus forskohlii Extract Attenuated the Beneficial Effect of Diet-Treatment on NASH in Mouse Model.

Obesity is one of the main causes of non-alcoholic steatohepatitis (NASH), which is associated with impaired liver functions including drug metabolism. Coleus forskohlii extract (CFE) is a popular ingredient of weight loss dietary supplements in Japan. In this study, we examined the effect of CFE on the treatment of NASH. C57BL/6 mice (male, 10-wk-old) were fed a NASH diet (high-fat, low-methionine, and choline-deficient diet) for 12 wk to establish NASH. Then, we examined the effect of 0.5% (w/w) CFE in diet during diet-treatment (change to control diet) and/or treadmill-exercise (45 min at 20 m/min, 5 d/wk) to improve NASH for 3 wk. After experimental period, lipids profiles and liver functional markers in the blood, and hepatic lipid content and major CYP subtype mRNA expression and activity in liver were measured. Diet-treatment, but not exercise decreased liver weight and hepatic lipid contents in NASH induced mice. CFE attenuated the effects of diet-treatment which reduced liver weight, even though body weight and adipose tissue weight were reduced. Further, CFE significantly increased liver microsomal CYP1A1, CYP1A2, CYP2C, and CYP3A activities in each condition, and CYP inductions were greater in diet-treatment group compared to those in exercise group. These results suggest that taking CFE should be avoided during diet-treatment of NASH, especially in patients under medication.

An educational intervention improved knowledge of dietary supplements in college students.

BACKGROUND: We have previously reported on the prevalence of dietary supplements among college students; it was deduced that their intake of supplements increased according to their grade (i.e., 13.1% in the first grade to 20.5% in the sixth grade). We also reported that some students had experienced adverse events in Japan due to their intake of these supplements. However, awareness of dietary supplements among college students remains limited, even among pharmaceutical students. Being appropriately educated about them is important for pharmaceutical students, both for themselves as well as for their future careers as pharmacists. METHODS: We conducted a lecture-based educational intervention about dietary supplements on 328 college students in Japan-184 from pharmaceutical science and 144 from environmental science or food and life science disciplines. The purpose of this study was to evaluate the effects of an educational intervention on college students' understanding of dietary supplements. The intervention involved a lecture that covered the quality of dietary supplements, how they differed from drugs, and a summary of their adverse events. The lecture was evaluated using a 14-question questionnaire. We then compared the pre- and post-intervention responses to the same questionnaire using a Wilcoxon signed-rank test. The questions were assessed using a Likert scale that ranged from "strongly agree" to "strongly disagree"; the latter being the preferred answer. RESULTS: Before the intervention had taken place, the students' understanding of dietary supplements was shown to be deficient. Conversely, post-intervention, their knowledge levels had significantly improved, especially concerning agreement on whether "Dietary supplements are safe because they are just food items". Pre-intervention, 2.7% strongly agreed and 37.5% agreed; post-intervention, 1.2% strongly agreed and 15.6% agreed. On whether "Dietary supplements made from natural ingredients or herbs are safe", at the pre-intervention stage 2.8% strongly agreed and 44.0% agreed and post-intervention, 2.2% strongly agreed and 16.9% agreed. On whether "Dietary supplements made from food items are safe", 4.0% strongly agreed and 43.6% agreed pre-intervention and 0.9% strongly agreed and 16.6% agreed post-intervention. Despite there being a greater number of pharmaceutical students who had a correct understanding of dietary supplements before the intervention, these students still showed improvement after the lecture. CONCLUSION: An intervention in the form of a single educational lecture has the capacity to improve college students' understanding of dietary supplements. It is important for pharmacists to be appropriately educated about dietary supplements when they consult with patients. We will evaluate the long-term effects of the intervention on the alumni (pharmacists) in a subsequent study.

[Method Verification for Vitamin D Analysis in Processed Foods Based on the Analytical Manual for the Standard Tables of Food Composition in Japan 2015 (Seventh Revised Edition)].

Considerable amounts of processed foods contain vitamin D (ergocalciferol (D2) and cholecalciferol (D3)) as food additives. For field surveys on food additives, the analytical method for vitamin D should be well-validated. However, the current official method in Japan cannot separately determine the concentrations of D2 and D3, whereas the method for the Standard Tables of Food Composition in Japan 2015 (STFC method) can. Therefore, in this study, we verified the applicability of the STFC method to processed foods. During the course of this research, we added some improvements to the original method. Spike and recovery experiments using vegetable juice, soymilk, and corn flakes as food matrices showed that the recovery rates (relative standard deviation) of D2 and D3 were 103-112% (4.7-12.6%) and 102-109% (2.4-21.8%), respectively, at the estimated method limit of quantification (EMLOQ) level; and 100-110% (4.0-7.4%) and 102-105% (3.8-4.8%), respectively, at 10 times the EMLOQ level. These results indicated that accuracy and precision of the modified STFC method were enough to determine dietary D2 and D3 as endogenous nutrients and/or food additives, and suggested that this method is appropriate for analyzing vitamin D concentrations in processed foods.

[Proficiency Testing Schemes for Food Nutrition Analysis in Japan (2017-2018)].

This paper deals with proficiency testing schemes for food nutrition analysis in Japan. In schemes in 2017 and 2018, 65 and 73 organizations participated, respectively, and more than 70% of the participants were public organizations responsible for a nutrition-labeling compliance test. The food matrices were pork and chicken sausages, and analytes were protein, fat, ash, moisture, carbohydrate, energy, sodium, salt equivalent, calcium (2018 only), and iron (2018 only). The organizations reporting inadequate laboratory values in one or more nutrients for mandatory declaration (energy, protein, fat, carbohydrate, or salt equivalent) were 11 and 15% of all organizations and 9 and 13% of public organizations in the 2017 and 2018 schemes, respectively. The approximate relative standard deviations for proficiency assessment (RSDr) were as follows: protein, 2%; fat, 3%; ash, 2%; moisture, 0.5%; carbohydrate, 9%; energy, 1%; sodium (salt equivalent), 4%; calcium, 7%; and iron, 7%. Notably, the large RSDr value for carbohydrate may cause inconsistency among laboratories in compliance tests for foods containing several grams or less of carbohydrate per 100 grams.

Comparison of CYP Induction by Coleus forskohlii Extract and Recovery in the Small Intestine and Liver of Mice.

We examined CYP induction and recovery at various doses of Coleus forskohlii extract (CFE) to assess potential drug interactions by a mechanism involving intestinal CYP. Mice were administered diets with various doses of CFE up to 0.5% (equivalent to 700-800 mg/kg body weight) for 2 weeks, then CFE was withdrawn for 3 d. Changes in CYP activities and mRNA expression in the small intestine and liver were then evaluated. CFE induced CYP in the small intestine at a higher dose compared to the liver; CYP3A was induced at 0.5% and 0.005% CFE in the small intestine and liver, respectively. There was no sex difference in CFE dose for CYP induction. CYP induction quickly reverted after withdrawal of CFE, especially for CYP3A, in the small intestine; whereas, a gradual recovery was observed in the liver. In conclusion, CFE induced CYP in the small intestine and liver; however, a higher dose of CFE was needed for the small intestine. Moreover, the induction was soon recovered, suggesting actual interactions of CFE with prescription drugs are unlikely to occur through CYP in the small intestine.

[Systematic Review of Case Reports on the Adverse Events Due to Health Food Intake by Cancer Patients].

Cancer patients use health foods (HFs) as complementary and alternative medicine, although the details of their adverse events (AEs) are unclear. We searched three databases [PubMed, "Igaku Chuo Zasshi", and Information System on Safety and Effectiveness for Health Foods website (https://hfnet.nibiohn.go.jp/)] for case reports on AEs related to HF intake in cancer patients published before October 2018. Of the matched reports, 76 studies and 92 patients (31 in Japan, 61 overseas) that met the selection criteria were included in this review. Thus, the severity of AEs and outcomes were not related to either the concomitant use of HF with cancer chemotherapy or cancer stages of patients. AEs caused by HF intake itself accounted for 87%, while drug-HF interaction accounted for 11%. According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, 70% of patients whose grades were identified had severe cases (grades 3 to 5). In Japanese patients, hepatic and respiratory disorders accounted for 52% of the severe cases. Cases were predominantly developed as a result of an allergic mechanism, and mushroom products were mostly used. Overseas, serious cases were induced by products that were already indicated for safety problems. Moreover, notable AEs were recognized, such as hypercalcemia, which were caused by intake of HF containing calcium, vitamin D, and shark cartilage, and bacterial infection caused by probiotic products. Analyzing the details of AEs related to HF intake can help health professionals and cancer patients prevent health hazards.

Identification of Compounds in Coleus forskohlii Extract Involved in the Induction of Hepatic CYP and Fatty Liver in Mice.

Coleus forskohlii extract (CFE), a popular weight-loss herbal product, induces hepatic cytochrome P450 (CYP) and fatty liver in mice; however, its main bioactive ingredient, forskolin, does not show such effects. To ensure the safety of CFE as a dietary supplement, identification of the compounds implicated in the induction of hepatic CYP and fatty liver is required. In this study, we separated a crude CFE extract into 5 fractions (Fr.) by column chromatography and administered the fractions to mice for one week to assess their ability to induce CYP and fatty liver. CYP induction was detected for all fractions, indicating that many compounds may be involved in CYP induction, while fatty liver was only detected for Fr. 2. Further isolation and purification of Fr. 2 by column chromatography identified 14-deoxycoleon U as a major compound and crocetin dialdehyde as a pigment compound. An in vivo mouse study revealed that crocetin dialdehyde had no effect on the liver and, as 14-deoxycoleon U was the major compound in Fr. 2, it is likely that the active compound inducing fatty liver in CFE is 14-deoxycoleon U. These findings will facilitate the preparation of standardized safe CFE ingredients for dietary supplements.

Tandem Cation/Anion Exchange SPE Cartridge Method for Sample Desalting for HPLC Analysis of Soluble Dietary Fiber: Development and Inter-laboratory Validation.

In HPLC analyses of soluble dietary fiber, desalting processes using open, mixed-bed ion-exchange columns are time-consuming and labor-intensive. We developed and validated a simple desalting method using tandem cation/anion exchange SPE cartridges. We found that combining Bond Elut Jr SCX (upstream) and Bond Elut PSA (downstream) cartridges provided adequate desalting of test solutions. The developed method was then validated in an inter-laboratory study. Five test samples were prepared by mixing food matrixes with purified soluble dietary fiber and treated to generate solutions to test the desalting process. These solutions were then analyzed by eight different laboratories. The results demonstrated that the developed method is simple and reliable for desalting samples containing 140 to 945 mg/100 mL of soluble dietary fiber in preparation for HPLC analysis of soluble dietary fiber.

Nationwide Online Survey Enables the Reevaluation of the Safety of Coleus forskohlii Extract Intake Based on the Adverse Event Frequencies.

The formulations of the functional ingredients of dietary supplements was studied with a small number of subjects, with a particular focus on their effectiveness, but not enough to evaluate their safety. In this regard, the reevaluation and estimation of the safe use of marketed products, with regards to their adverse event (AE) frequencies, are important. To address this issue, a post-marketing nationwide online survey was conducted for the herbal ingredient Coleus forskohlii extract (CFE), a popular weight-loss ingredient. The questionnaire included product names, adherence to the claimed amount, and AE experiences. The safe intake amount was estimated by the relationship between the claimed amount of CFE and the frequencies of AEs of each product. The number of users who experienced AEs was 75 (10.5% of all users). Gastrointestinal symptoms accounted for 92.0% (n = 69) of all AEs, and diarrhea alone accounted for 81.3% (n = 61). The amount of CFE was significantly associated with the occurrence of diarrhea (p = 0.005). The fitted curve showed that the safe intake amount of CFE was less than 250 mg/day; however, considering its effectiveness, 500 mg/day of CFE might be acceptable. In conclusion, nationwide online surveys of users enable us to confirm and reevaluate the safety of herbal supplements.

Nationwide Online Survey to Complement the Current Voluntary Reporting System for Adverse Events Associated with Dietary Supplements: Application to the Case of Skin Manifestations.

The current adverse event reporting system for dietary supplements lacks the ability to collect and analyze ongoing case reports in sufficient numbers to detect health issues. We conducted an online survey to collect data on skin manifestations due to supplement use in consumers and to identify the suspected products and ingredients. An online survey was conducted among 63,737 dietary supplement users in 2016. Those who self-reported experiences of skin anthema or itching caused by supplement use and recognized a causal relationship as almost certain (0.8%) were invited to provide further details of symptoms and products. Most of the users experienced mild symptoms with "itching and/or rash of body part." After the onset of skin manifestations, 69.3% ceased supplement use, while 26.6% continued supplement use, including those who reduced the amount or frequency of use. Respondents who visited the hospital in response to symptoms accounted for 26.0%, while 53.3% did not seek treatment. The products used were identified in 155 of 300 eligible respondents. Although those products were composed of multiple ingredients, the accumulated data suggested that cutaneous symptoms were related to the following constituents: "Peptides or animal by-products" (31.0%), "Herbal/Botanical" (23.2%) and "Fats and lipid" (13.5%). Conducting an online survey to elicit information directly from consumers identified components of supplements that are involved in skin manifestations that could lead to serious damage, and may fill a void in the current adverse event reporting system.

The Prevalence of Dietary Supplement Use Among Elementary, Junior High, and High School Students: A Nationwide Survey in Japan.

The prevalence of dietary supplement use, such as vitamins, minerals, or fish oil, has increased among children in Japan; however, whether children are using dietary supplements appropriately remains unclear. This study aimed to determine dietary supplement use among children. In August 2017, a nationwide internet preliminary survey of 265,629 mothers aged from 25 to 59 years old was undertaken. Of these, 19,041 mothers of children attending either elementary school, junior high school, or high school were selected. Among them, 16.4% were currently providing their children with dietary supplements and 5.2% had previously given dietary supplements to their children. The prevalence of dietary supplement use was higher in boys than in girls, and the prevalence increased according to their grade. A total of 2439 participants were eligible to undertake a targeted survey on dietary supplement use. Dietary supplements were being taken to maintain health, supplement nutrients, and enhance growth in both boys and girls, and many children (37.5%) were provided with vitamin and mineral supplements. Mothers mainly obtained information concerning dietary supplements via the internet, and supplements were purchased in drug stores or via the internet. The prevalence of dietary supplement use in mothers was 65.4% and may be associated with the prevalence rates in children. Some mothers reported adverse events (3.6%) in their children, such as stomachache, diarrhea, nausea and vomiting, and constipation. The cause-and-effect relationships for adverse events were not clear, but some children were given products for adults. Children are more influenced by dietary supplements compared to adults. To prevent adverse events due to inappropriate use, parental education concerning dietary supplements is essential.

[Nationwide Online Survey Method to Estimate Ongoing Adverse Events Caused by Supplement Use: Application to Diarrhea].

The current adverse event reporting systems are inadequate to prevent potential health damage caused by dietary supplement use, and a better case-collecting system is needed. The aim of this study was to examine whether online surveys would be a useful methodology for estimating ongoing adverse events, focusing on diarrhea as a model symptom. We used four online survey companies and requested that they administer the same questionnaire to their registrants regarding experiences of adverse events associated with supplement use and details of diarrhea symptoms, as well as the product and ingredient names of suspected supplements. Of 78,220 dietary supplement users, 9% to 25% reported experiencing adverse events in the previous year. A total of 723 participants who answered affirmatively about a putative causal relationship between supplement use and the onset of diarrhea and who clearly identified the product and/or ingredient were eligible for final analysis. Comparisons among the survey companies showed differences in the proportions of reported symptoms; however, the rank orders were consistent in the preliminary survey. Also, when analysis was limited to specific participants from a full-scale survey, even the numerical values of the proportions were consistent among the four companies. Herbal/botanical ingredients, specifically Coleus forskohlii, were the ingredients most frequently reported to be associated with diarrhea. These results indicate that online survey can be a useful method to complement the current system for estimating ongoing adverse events and identifying the responsible supplements.

[Improved Reliability of Vitamin Analysis in Foodstuffs Using a Microbiological Assay Method: Construction of Calibration Curves Using Logistic Modeling].

Vitamins are essential nutrients for human beings. Therefore, accurate determination of vitamin levels in foodstuffs is vital to confirm the proper intake of vitamins. The microbiological assay (MBA), which is used worldwide for the determination of several vitamins in foodstuffs, is very sensitive and can determine ng/mL levels of vitamins. However, the correlation between vitamin concentrations in a sample solution and the plotted growth is usually shown as a sigmoid curve. Therefore, a calibration curve derived from a linear regression may lead to error. In this study, we evaluated the effects of various models (linear, quadratic, and cubic regression models and a four-parameter logistic model (4PLM)) for calibration curve construction on the determination of vitamin B6 in infant formula. Among the four models, the calibration curve constructed with 4PLM was the most reliable for vitamin B6 determination. Moreover, the calibration curve based on 4PLM showed robustness for extrapolation; even if the vitamin concentration in the sample solution deviated from the range of the standard solution, a reasonable result could be obtained. Similarly, the 4PLM calibration curve was the most reliable for niacin determination. We conclude that 4PLM should be used for calibration curve construction to improve the reliability of vitamin determination in foodstuffs using MBA.

[Personality and dietary supplement use among Japanese female students].

Objectives　The purpose of this study was to examine the relationship between dietary supplement use and personality traits among Japanese female students.Methods　A cross-sectional questionnaire survey was administered to 230 female university or junior college students in October and November 2015; 228 students responded. The questionnaires inquired regarding the usage of dietary supplements and attitudes about dietary supplements, as well as the healthy eating literacy (HEL) scale and the Big Five personality traits. In total, 124 respondents completed the survey. The Mann-Whitney U test, Kruskal-Wallis test, chi-square test, and Spearman's correlation coefficient were used to examine dietary supplement-personality relationships.Results　Overall, 19.4% of students reported using dietary supplements. Supplement users had high extraversion scores compared with non-users. Attitudes about dietary supplements and HEL were not associated with personality traits.Conclusion　Personality traits influenced dietary supplement use, although limitedly.

[Notable Adverse Events Associated with Concomitant Use of Health Foods and Drugs Derived from the Analysis of HFNet Data on the Safety and Effectiveness of Health Foods].

Health foods are commonly consumed at their own discretion by patients with various diseases who are also being treated with conventional drugs. Both health foods and drugs are diverse, and enormous numbers of possible combinations exist, so that it is very difficult to identify adverse events that may occur due to their interactions. Here, we analyzed the characteristics of adverse events related to the concomitant use of health foods and drugs using data from the "Information system on safety and effectiveness for health foods (HFNet)" website (https://hfnet.nibiohn.go.jp/) compiled by the Food Function and Labeling Department of the National Institute of Health and Nutrition of Japan. We identified 64 reports and 71 patients, and characterized them according to symptom severity and drug classification. The analysis revealed that symptoms of liver dysfunction were mainly reported in patients receiving high-risk drugs, such as antiepileptic, antineoplastic, antiarrhythmic, and antithrombotic drugs, concomitantly with health foods or drugs. However, journal articles describing health food and drug interactions generally did not provide sufficient information about the ingredients of the health foods.