[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.

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.

[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.

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.

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.

[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.

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.

[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.

[Analysis of Safety Alerts Associated with Dietary Supplements from Japan and Overseas].

The prevalence of dietary supplement use has increased in Japan, and consumers can purchase supplements from foreign countries through the internet. Therefore, it is important to consider both domestic and overseas safety alerts to prevent adverse events associated with dietary supplement use. We have been collecting global safety alerts associated with dietary supplements and providing this information to the public via the "Information system on safety and effectiveness for health foods (HFNet)" website. In this study, we analyzed the characteristics of safety alerts from 2010 to 2016 in HFNet (total: 2,124 alerts). The most common reason for alerts was illegal adulteration with pharmaceutical substances (85%), and sexual enhancement or weight loss products accounted for 68% of all alerts. Most alerts were based on market surveillance reports or recall information. However, 181 adverse event reports were identified, and most of them were related to weight loss or disease treatment in patients. In Japan, a majority of the adverse events was caused by products intended for weight loss or purchased online, and young female users were commonly involved. These findings should be helpful for prevention of adverse events associated with dietary supplement use.

The Prevalence of Dietary Supplement Use among College Students: A Nationwide Survey in Japan.

To clarify the prevalence of dietary supplement use among college students, we conducted Internet-based nationwide questionnaire surveys with 157,595 Japanese college students aged between 18 to 24 years old who were registrants of Macromill Inc. (Tokyo, Japan). Among the 9066 respondents (response rate 5.8%), 16.8% were currently using dietary supplements. The prevalence of dietary supplement use did not differ significantly between males (17.1%) and females (16.7%). However, it increased according to their grade (13.1% to 20.5%), and it was higher in medical and pharmaceutical college students (22.0%) compared to others (16.7%). The main purpose of dietary supplement use was for the health benefits in both males and females. Other reasons were to build muscle in males, and as a beauty supplement and for weight loss in females. According to the purpose of dietary supplement use, the most commonly-used dietary supplements were vitamin/mineral supplements in both males and females, then protein and weight loss supplements in males and females, respectively. Although most students obtained information about dietary supplements via the Internet, they typically purchased the supplements from drug stores. Of the students surveyed, 7.5% who were currently using or used to use dietary supplements experienced adverse effects, with no significant difference between genders (8.8% in male, 7.0% in female). In conclusion, the prevalence of dietary supplement use increased with grade among college students in Japan. Some of them experienced adverse effects. Education may be important to prevent adverse effects resulting from supplement use in college.

Sources of Information about Health Foods among Elderly People-Comparison of Internet and Paper Survey Results.

The prevalence of health foods is increasing in Japan, especially among elderly people. The internet is widely used as an information source, but it is not clear whether elderly people get information about health foods via the internet or not. To clarify this issue, we conducted two questionnaire surveys; one on a website (internet survey) and one in the local community (paper survey). The internet survey showed that a lot of elderly people use the internet to get information and also to purchase health foods. On the other hand, paper survey showed that a smaller proportion of elderly people used the internet, compared to the internet survey. Instead, they got information from their friends, health-care professionals, or various media sources, such as television, newspapers and magazines. Our results indicate that many elderly people don't use the internet to get information about health foods. Adequate ways to inform them about health foods are needed to reduce adverse events associated with health food use.

Status of "Food with Function Claims"-Internet Survey on Consumers, Physicians and Pharmacists a Year Later.

"Food with Function Claims" was established on April 1st 2015. In the present study, we conducted internet surveillance to examine recognition of "Food with Function Claims" among consumers (n=2,060), physicians (n=515), and pharmacists (n=515). The ratio of recognition of "Food with Function Claims" was 81% among consumers, 93% among physicians, and 98% among pharmacists. However, only 16% of consumers, 23% of physicians, and 44% of pharmacists correctly understood the characteristics of "Food with Function Claims". Only 12% of consumers were using or have used "Food with Function Claims". Among "Food with Function Claims" users, 26% checked the information about "Food with Function Claims" on the website of the Consumer Affairs Agency, Government of Japan. Some of them used "Food with Function Claims" for treatment their diseases. In addition, some of them used "Food with Function Claims" and medicines concomitantly without consulting their physicians or pharmacists. Consequently, only 8% of physicians and pharmacists were asked about dietary supplement use by their patients, and 2% of physicians and pharmacists had consultations with their patients on adverse events associated with using "Food with Function Claims".

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.

[A Systematic Review to Identify Unacceptable Intake Levels of Vitamin B6 among Patients Taking Levodopa].

The interaction of levodopa and vitamin B6 is a well-known issue. This study investigated the incidence of unacceptable intake levels of vitamin B6 among levodopa users by means of a systematic review. We searched two databases (PubMed and "Igaku Chuo Zasshi") for articles about adverse events due to the interaction of levodopa and vitamin B6 published up to August 2017. Of 98 citations retrieved, 11 studies met the selection criteria. The results indicated that a vitamin B6 intake level of more than 50 mg/day could reduce the efficacy of levodopa. The recommended intake of vitamin B6 for Japanese adults is 1.4 mg/day for men and 1.2 mg/day for women. Therefore, the acceptable intake of vitamin B6 for levodopa patients would be within the range of the recommended intake level, which is also within the usual range in foods in Japan, except for dietary supplements or health foods. Levodopa users should be cautious about taking dietary supplements and over-the-counter drugs.