1. Introduction
With the rapid increase in the senior population in Japan, chronic diseases associated with aging, such as diabetes mellitus, cardiovascular disease, hypertension, osteoporosis, and cancer have become a widely recognized social issue. Against this background, an increase in health consciousness prompts people to use dietary supplements to maintain health and prevent diseases. Most people use vitamin or mineral supplements, whereas other herbal extracts (e.g., blueberry, coleus forskohlii, ginkgo, or green tea) and ingredients (e.g., collagen, catechins, fish oil, glucosamine, hyaluronic acid, and isoflavones) are also popular in Japan. People tend to believe that dietary supplements are as safe as food and as beneficial as medicine.
The beneficial effects of food and its nutrients and other ingredients have been recognized for a long time. Previously, people obtained nutrients and other ingredients only as foods, such as vegetables, fruits, fish, meat, tea, and other items. Over time, manufacturers learned to extract and condense some of the specific nutrients or ingredients in food and offer them as dietary supplements in the form of tablets, capsules, or powders. The concentrated ingredients in dietary supplements carry not only the benefits but also the risk of toxicity, interaction with drugs, and adverse reactions compared with the ingredients in whole foods [
1]. However, manufacturers tend to emphasize key characteristics of their products and promote sales using attractive claims. In addition, in some cases, manufacturers claim that medicines are more likely than dietary supplements to cause side effects, because medicines are synthetic compounds, whereas dietary supplements are made from natural substances and thus safe and suitable for everybody. Currently, there is insufficient evidence that dietary supplements improve disease in humans, and if patients turn to dietary supplements instead of medicines, health problems might occur. Indeed, adverse effects caused by dietary supplements, especially hepatotoxicity associated herbal supplement use, are reported worldwide [
2,
3,
4].
Regulation of dietary supplement in Japan is more complicated compared to other countries such as the USA or European countries. In 1991, the Ministry of Health, Labour and Welfare set up the Food for Specified Health Uses to provide people with accurate health information about foods. The current Japanese system for regulation of health foods is called Food with Health Claims and is made up of two categories: (1) “Food with Nutrient Function Claims” and (2) “Food for Specified Health Uses”. Most of “Food for Specified Health Uses” products are the form of regular food, such as tea, beverage, yogurt, and flakes. On the other hand, except for “Food with Health Claims”, laws for dietary supplements are not defined in Japan. This means that most dietary supplements on the market are considered the same as other foods, even if they are in the form of capsules or tablets [
5,
6].
Consumers tend to have only a vague understanding that dietary supplements are different from medicines, and some consumers use dietary supplements as medicines to treat specific diseases in Japan. Several reasons contribute to this inappropriate use of dietary supplements. First, there is no clear, official definition of dietary supplements in Japan. Because of this, many dietary supplements claim to treat specific diseases, especially cancer, even though such claims are illegal in Japan. Secondly, dietary supplements available as capsules or tablets look like medicines and thus are often thought to be as effective as medicines. Thirdly, consumers do not understand the properties of dietary supplements. Physicians are concerned about the use of dietary supplements by their patients, because of the possibility of dietary supplement–drug interactions [
7]. In particular, dietary supplements may interact with some medicines as well as affect anaesthesia and bleeding during surgery [
8].
Dietary supplements are helpful to complement nutrition in not only healthy subjects but also patients. However, if patients use dietary supplements to treat diseases without consulting physicians, it may cause health problems. This study used a self-administered questionnaire to clarify awareness and use of dietary supplements among patients in Japan.
2. Methods
2.1. Subjects
Subjects included 2732 people, who either attended health food seminars (Iwate, Ibaragi, Fukushima, Tokyo, Kanagawa, Shizuoka, Gifu, Wakayama, Fukui, Okayama, and Ehime), visited pharmacies (Tokyo, Shizuoka, Okayama), or were admitted to hospitals (Iwate, Tokyo, Saitama, Chiba, Shizuoka, Aichi, Okayama, Fukuoka, Nagasaki, Miyazaki, Saga, Kumamoto, Kagoshima) from January to December 2012. To clarify the recognition and use of dietary supplements among patients, we asked all subjects about their medical status and divided into three categories, admitted patients, ambulatory patients, and healthy subjects. Healthy subjects were defined as people who were not hospitalized or making regular visits to the hospital. This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects/patients were approved by the Research Ethics Committee of the National Institute of Health and Nutrition and each participating institute.
2.2. Definition of Dietary Supplements
Dietary supplements are well defined in the USA and European countries, because they are regulated by law, but they are not regulated in Japan. Dietary supplements were usually recognized in the form of capsules, tablets, powders, or liquid. However, some dairy or soybean products are also produced as dietary supplements, even if they are in the form of regular foods. Thus, we did not define a specific form for dietary supplements in this survey. Dietary supplements were defined as foods, other than vegetables and fruits that subjects thought would have beneficial effect on their health.
2.3. Questionnaire
The questionnaire included demographic characteristics (sex and age), information on use of supplements, awareness of dietary supplements (safety, price, effectiveness, substitute for medicines, and co-administration with medicines), purpose (maintenance of health, nutritional support, prevention of disease, treatment of disease, beauty, no specific purpose), number of dietary supplements used, realization of beneficial and adverse effects, and type and their situation of medications. In addition, the questionnaire asked whether subjects informed their physicians of their use of dietary supplements.
2.4. Statistical Analysis
Differences in demographic characteristics or supplement use among admitted patients, ambulatory patients, and healthy subjects were tested using the χ2 test or Kruskal-wallis test with Bonferroni correction. Univariate analysis for the association of supplement use with various variables in the patients and healthy subjects was done using the χ2 test. Multivariable analysis was also done using the logistic regression analysis adjusted for sex and age. P values less than 0.05 in χ2 test and 0.0167 in Kruskal-wallis test were considered significant. A statistical analysis was performed using SPSS 18.0J for Windows (IBM Co., Armonk, New York, NY, USA).
4. Discussion
In this study, we clarified that not only ambulatory patients but also admitted patients used dietary supplements, and they used it for treatment their diseases. These patients also took medicines concurrently without consulting physicians.
In the United States, 48.8% of people used dietary supplements from 2007 to 2010 [
10]. Previous reports show that use of dietary supplements in Japan has increased over time from 10.9% in 2001 [
11], 11.0% in males and 16.4% in females in 2003 [
12], and 45.8% in older adults in 2008 [
9], even if factors such as sex, age, socioeconomic status, and health-related characteristics are known to affect use of dietary supplements [
10,
13,
14,
15,
16]. In addition, recognition also affects dietary supplement use. Dietary supplements were not regulated in Japan. Most dietary supplements are the form of capsules, tablets, powders, or liquid, and some are the form of regular foods in Japan. In this situation, some people take dietary supplements without consideration for the risk of them. In these days, as dietary supplement use increases, associated health problems also increase. Health problems associated with dietary supplement use have two causes. One is use of low quality or illegal products that contain drug ingredients [
17,
18]. To avoid health problems caused by these products, the Japanese government constantly surveys and checks these products on websites and retail stores. Another is inappropriate use of dietary supplements, including excessive intake and concomitant use of various dietary supplements and/or medicines. In particular, inappropriate use of dietary supplements in patients may be associated with severe health problems. To avoid health problems caused by inappropriate use, communication between patients and physicians are important.
It is recognized that infants, children, pregnant women, the elderly, and patients are susceptible to dietary supplements. It is important to identify dietary supplement use in these high-risk groups and to stop inappropriate use. Inappropriate use of dietary supplements by Japanese children [
19] and pregnant women [
20] has been defined. In Japan, most children have a good nutritional state and thus do not require dietary supplements. On the other hand, folic acid supplements are recommended for pregnant women because it is difficult to obtain adequate amounts of folic acid from food [
21]. However, we confirmed that pregnant women could not avail of dietary supplements appropriately [
20]. Aside from children and pregnant women, many older people in Japan appear to use dietary supplements; some of them use dietary supplements for treatment of diseases [
22]. In this study, we investigated the awareness and use of dietary supplements among Japanese subjects.
Our results showed that 36.8% of ambulatory patients and 17.7% of admitted patients took dietary supplements with their medicines and thought that this practice was safe. However, many reports indicate that dietary supplements interact with medicines. The most well-known example is St. John’s wort (
Hypericum perforatum L.). St. John’s wort contains hyperforin, which increases the expression of cytochrome P450 (CYP), especially CYP3A4, and affects drug metabolism in the liver [
23]. Other herbs (e.g., black cohosh, coleus forskohlii, echinacea, garlic, ginkgo, ginseng, green tea, kava, and milk thistle) [
24,
25,
26,
27,
28] and ingredients (e.g., catechins [
29], curcuminoids [
30], isoflavones [
31], quercetin [
32], polyphenols [
33], and resveratrol [
34]) also affect drug metabolizing enzymes.
To avoid interactions between prescription medications and dietary supplements, physicians need to know whether their patients use dietary supplements or not. However, as shown in this survey, most patients do not discuss these supplements with their physicians, which is consistent with previous reports [
35]. One reason for this lack of discussion is that most physicians do not ask about dietary supplement use, probably because the consultation time for each patient is limited. In addition, 5 admitted patients answered “Doctors never ask about dietary supplements use” (
Table 6), it means that some of physicians did not care whether their patients used dietary supplements or not. It might be caused by insufficient recognition of dietary supplements. At the same time, most patients do not think that dietary supplements will affect their medication. Thus, both patients and physicians do not fully recognize the risk of interactions between dietary supplements and medications [
36]. It is also reported that both of patients and physicians are poorly understood the regulation of dietary supplement in the USA [
37], even though dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) under Dietary Supplement Health and Education Act. As dietary supplements are not as safe as they believe [
38], education for both physicians and patients is important in order to avoid health problems associated with dietary supplements.
Consistent with a previous internet survey in Japan, 3.3% of all subjects experienced adverse effects by using dietary supplements, even if most cases were not severe. In this survey, we did not ask which type of product was used. Thus we could not determine any relationship between dietary supplements and adverse effects. However, many subjects used several dietary supplements and medicines concurrently. Even if we asked which type of product was used, it would be impossible to determine the cause of health problems. To avoid unexpected health problems caused by dietary supplements, patients should not use dietary supplements for disease treatment or concurrently with medicines without consulting by physicians.
There are some limitations in this study. The number of admitted patients was lower than the number of ambulatory patients or healthy subjects, because cooperation with primary doctors was essential to conduct this survey in admitted patients. In addition, we did not ask type, periods, and frequency of dietary supplements use or medications. So, we could not evaluate the exact risk of concomitant use of dietary supplements and medicines in this study. Further investigations are needed.