Download Current Marketplace for Probiotics: A Japanese Perspective

SUPPLEMENT ARTICLE
Current Marketplace for Probiotics:
A Japanese Perspective
Harunobu Amagase
FreeLife International, Phoenix, Arizona
In Japan, probiotics are available as both foods and drugs. Unlike in the United States, probiotics have a long
history of cultural acceptance and safe use in Japan. Sales are booming, which may reflect the inception of
the regulatory category “foods for specialized health use” (FOSHU), which permits labeling with claims that
describe health benefits. A total of 65 probiotic products, containing 16 different strains, are listed among the
579 FOSHU products. Since the US market for probiotics is still small, it has substantial room to grow.
In Japan, fermentation using various microorganisms
is a traditional method to produce sake (wine made
from rice), miso (soybean paste), natto (fermented soybean), pickles, and many other products. Fermented
dairy products, which were reintroduced to Japan ∼300
years ago after an extended absence, are also quite popular [1]. In the early 1990s, Japan established the regulatory category “foods for specialized health use” (FOSHU), which permits labeling with health claims on
foods that meet specific requirements for safety and
efficacy [2]. As of 1 September 1991, to be called “FOSHU,” products must be approved by the Japanese
Minister of Health, Welfare, and Labor. Products containing ingredients identical to those in approved products must still undergo this process. The categories of
claims include blood pressure, cholesterol, triglycerides,
blood sugar, bone minerals (especially calcium), and
dental health.
Recently, Japan has witnessed a significant increase
in the market for health foods, including FOSHU products, which has outpaced sales of over-the-counter
(OTC) drugs. In 2005, the Japan Health Food and Nutrition Food Association estimated the Japanese market
for probiotics at US$5.3 billion, up from $1.12 billion
Reprints or correspondence: Dr. Harunobu Amagase, FreeLife International, 3925
E. Broadway Rd., Ste. 201, Phoenix, AZ 85040 ([email protected]).
Clinical Infectious Diseases 2008; 46:S73–5
2008 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2008/4603S2-0005$15.00
DOI: 10.1086/523338
in 1997. As of 27 February 2006, a total of 579 FOSHU
products have been approved, including 65 probiotic
products containing ⭓1 of the 16 approved bacterial
strains: Lactobacillus rhamnosus GG, Bifidobacterium
longum BB536, Lactobacillus delbrueckii subsp. bulgaricus 2038, Streptococcus salivarius subsp. thermophilus
1131, Lactobacillus casei Shirota, Bifidobacterium breve
Yakult, Bifidobacterium lactis FK120, B. lactis LKM512,
Lactobacillus acidophilus CK92, Lactobacillus herbeticus
CK60, L. casei SBR1202, Lactobacillus gaseeri SP, Bifidobacterium SP, L. casei NY1301, Lactobacillus LC1, and
B. lactis Bb-12 [2, 3].
In recent years, Japan has undergone regulatory reform. One of the driving forces behind these changes
has been the country’s rising costs of health care [4].
Ward and Piccolo summarized the current situation by
noting that, “[l]ike most industrialized countries, Japan
is faced with a rapidly aging population and a declining
birthrate” [5]. In 2005, people aged ⭓65 years represented 19.9% of Japan’s population; however, this segment is predicted to increase to 26.0% by 2015 [6].
The increase in elderly persons combined with Japan’s
stagnant and slow economic growth are creating a financial crisis for the country’s health care system [5].
Government deregulation of some OTC drugs has
been used as a means to reduce health care costs. Some
of the OTC drugs with well-established safety records
have been reclassified as the category of “quasi-drugs”
or as functional foods. These products are no longer
limited to being sold at drug stores and pharmacies but
can be sold anywhere, including convenience stores,
Probiotics in Japan • CID 2008:46 (Suppl 2) • S73
grocery stores, and kiosks at train stations, without a pharmacist’s supervision. The category of drugs for gastrointestinal
health is one that was deregulated [7]. Biofermin S (Biofermin
Pharmaceutical), which contains live Bifidobacterium bifidum,
Streptococcus faecalis, and L. acidophilus, is one popular product
for treatment of diarrhea. It was transferred to the quasi-drug
(lyaku-bugaihin) category, which represents products with mild
effects on the body.
Japan is also encouraging the public to adopt healthier lifestyles as another means to reduce spending for health care [8].
Measures include the implementation of antismoking campaigns, the promotion of self-medication, and the use of health
foods to prevent or reduce the risk of disease.
Japan’s regulatory classification system is shown in figure 1
[2]. Health foods, represented by the category “foods with
health claims” (which includes the categories FOSHU and foods
with nutrient claims) must undergo approval based on the
Nutrition Improvement Act (section 12-1). These products
contain ingredients that influence physiological functions of
the body and can be used to maintain health and/or to achieve
specific health effects. For example, some probiotic foods claim
to maintain gastrointestinal health.
Probiotics are used today in many major Japanese hospitals
to treat gastrointestinal disorders, such as diarrhea and constipation, and symptoms related to antibiotic use. An example of
one such product, marketed by Wakanuga, contains 3 strains: L.
acidophilus KS-13, B. bifidum G9–1, and B. longum MM-2 [9,
10]. These strains are sold as a prescription drug, an OTC drug,
and a quasi-drug. To support the marketing of this product in
all these categories, the following information was determined:
efficacy [11–14], stability [15] (Food Products Laboratory, Portland, Oregon, personal communication), resistance to stomach
acids [12, 16, 17] (Food Products Laboratory, Portland, Oregon,
personal communication), implantation (colonization) [18], adherence to the gastrointestinal tract [19], and in vivo distribution
and recovery [20].
Health targets for probiotic FOSHU marketed in Japan include gastrointestinal conditions, immunity, allergy, cold and
influenza-like symptoms, cholesterol levels, blood pressure levels, and diabetes. Recent correspondence with Japanese authorities highlights the current and future directions for probiotics in Japan (Japanese Regulatory Authority, personal
communication):
1. Probiotics (lactic acid–producing bacteria) are used as
medicines and can be used as foods without medicinal claims.
2. As foods, probiotics have no specific restrictions. However, fermented milk or lactic acid drinks are required to have
a lower limit of lactic acid bacteria.
3. If probiotics are marketed as foods, efficacy claims are
prohibited on the labeling. To make claims about efficacy, one
must obtain special permission from the Ministry of Health
and Welfare for the product to be considered FOSHU, for which
substantiation of efficacy and safety is mandatory.
4. Good manufacturing practices are required for drugs but
not for foods.
On the basis of the Japanese experience, there are issues that
the United States will need to address with regard to probiotics.
Good manufacturing practices, including regulatory audits,
should be required for probiotics. Testing should address stability and cell viability, which are important not only for shelflife determination but also for efficacy. Cell viability is determined during stability testing, and numbers of viable cells
should be included on the label, reflecting the numbers at the
time of consumption, not at the time of manufacture. Because
probiotics exert their effects through the secretion of substances
such as vitamins and bateriocins, viable-cell counts reflect this
capacity. The source of the cell line is also important. It may
affect how the strain implants in the luminal epithelial cells of
the human intestinal tract, which can, in turn, influence the
probiotic efficacy. Efficacy should be presented in scientific
publications.
Figure 1. Regulatory positioning and classifications of food and drugs in Japan. Adapted from [2], with permission from Elsevier.
S74 • CID 2008:46 (Suppl 2) • Amagase
To date, Japan has been the global market leader in probiotics. Although safety considerations remain a concern of the
US medical and scientific communities, most probiotics sold
today as FOSHU in Japan and as foods or dietary supplements
in the United States and Europe have a long history of safe
use. With more education about probiotics, in conjunction with
new scientific findings and changing consumer demands and
social attitudes, the US market, currently estimated at $700
million, is poised to expand [21].
Acknowledgments
Supplement sponsorship. This article was published as part of a supplement entitled “Developing Probiotics as Foods and Drugs: Scientific and
Regulatory Challenges,” sponsored by the Drug Information Association,
the National Institutes of Health National Center for Complementary and
Alternative Medicine (1R13AT003805-01 to Patricia L. Hibberd), the California Dairy Research Foundation, Chr. Hansen, the Dannon Company,
General Mills, Institut Rosell, and Yakult International.
Potential conflicts of interest. H.A. was an employee of Wakunaga of
America, a marketer of probiotic products, at the time of presentation of
this work.
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