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Health claim and evidence in health food in Japan: vocabulary and law

International Conference and Exhibition on Nutraceuticals and Functional Foods (ISNFF) 2011

16 November 2011, Sapporo, Japan

Kiichiro TSUTANI MD, PhD津谷喜一郎

Dept. of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo

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Health Technology Assessment Report of GlucosamineNational Evidence-based Healthcare Collaborating Agency (NECA), Seoul, 2010

By systematic review, that there was lack of data to reach conclusions that glucosamine is effective for treatment and prevention of osteoarthritis.

Bae SC. Glucosamine and chondroitin products: Are they being used appropriately?: NECA News letter EVIDENCE & VALUE 29. Sep. 2010; 20-1 http://neca.re.kr/ebook/vol4/eng/vol4_eng_all/EBook.htm

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Dr. Dae Seog HEO, SNU

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Glucosamine not as “active ingredient”(有効成分)in OTC drug in Japan, but as “additive” (添加剤)

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Same brand name “Flexpower” in both as OTC drug and “so-called” health food

OTC drug(No information of glucos-

amine in the label)

健康補助⾷品(“health supplementary food”)

A kind of “so-called” health food

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“栄養補助食品”(Nutritional supplementary food) as “so-called” health food

Words: Sitting, standing and walking Image: knee pain

Questions: - What is people’s perception of this product ?- How people recognize this product ?

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Ethical glucosamine in ROK

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Package insert of Ethical glucosamine in ROK

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亜州薬品工業株式会社

OTC Reimbursed by nationalhealth insurance in ROK

Glucosamine

Binex 株式会社

OTC Not reimbursed by national health insurance in ROK

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Glucosamine: same evidence, different policies

Drug

Foodethical OTC

Reimbursem

ent

No ItaliaEngland

GermanyScotlandSwedenIrelandKorea

Japan (health food)U.S.A. (dietary supplement)

Canada (nutritional product)Austria (complementary medicine)

Malaysia (health supplement)Singapore (health supplement)

Korea (health supplement)

Yes KoreaTaiwan

Thailand

Korea

Dr. Dae Seog HEO, SNU and revised by TSUTANI K

My findings

• Different regulatory categories on same evidence exists even in one country

• Different words and/or graphic image appeals “health claim”

• Rich vocabulary and image !• Need people’s perception study• “How people distinguish “true” health

claim from fake/quasi health claim ?”

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Requirements for physiological conditions of subjects for human clinical study for FOSHU

（１）CholesterolTotal cholesterol in serum is essentially be between 200～240mg/dL、and LDL cholesterol must be between 120～160mg/dL ; duration of study must be longer than 12 weeks

（２）TriglycerideTriglyceride in serum is better to be somewhat higher those of rule and between 120～200mg/dL of fasting subjects and the study is continued for at least 12 weeks

（３）Blood pressureEssentially, subjects with normal higher blood pressure, low risk and middle risk high blood pressures are objects and the study is continued longer than 12 weeks

（４）Blood sugarAccording to the criteria, the fasting blood sugar levels are judged as bordering type diabetes or bordering by sugar loading. Study should be continued for longer than 12 weeks

（５） Body FatThe study must be carried out separately between male and female and classified depended on ages, and obesity criteria is 1 according to the Japan Obesity Society （BMI 25≦～＜30）. The study must be carried out for longer than 12 weeks

Requirements for clinical studies for FOSHU

• Randomized placebo controlled study• Subject number must be meet to statistically significance

(probably n = 100 – 200)• Enough duration of study to obtain the statistically

significant difference (≥ three months)• Clear endpoints• Exclude children, pregnant• Sample must be identical to the product which will be on

market• P-value for statistical analysis must be less than 5%• All clinical studies must be carried out according to

Helsinki Declaration• Approval by the Ethical Committee

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15Regulatory Systems of Health Claims in Japan. Food Labeling Division, Consumer Affairs Agency (CAA), June 2011 http://www.caa.go.jp/en/pdf/syokuhin338.pdf

Model claim: Helps lower cholesterol level.

「本品は、コレステロールの吸収を抑え、血中コレステロールを低下させる働きのあるキトサンを配合しています。コレステロール値が高めの方や気になる方の食生活の改善に役立ちます。」

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“Good for improving dietary habit for those having relatively high serum cholesterol level or those concerning cholesterol level”

Example 1

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Model claim: For those with high blood pressure.

「本品はゴマペプチドを含んでおり、血圧が高めの方に適した飲料です。」

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“Good for those having relatively high blood pressure”

Example 2

Model claim: Promote calcium absorption.Supports bone health

「本品はフラクトオリゴ糖の作用により、丈夫な骨をつくるカルシウムの吸収が促進されるよう工夫された飲料です。」

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“Make bone strong by efficient calcium absorption”

Example 3-1

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Model claim: Promote calcium absorption.Supports bone health

「この食品はカルシウムを豊富に含みます。日頃の運動と適切な量のカルシウムを含む健康的な食事は、若い女性が健全な骨の健康を維持し、歳をとってからの骨粗鬆症になるリスクを低減するかもしれません。」

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“Daily exercise and healthy diet containing adequate dose of calcium maintain bone health and may reduce risk of osteoporosis in the elderly age.”

Example 3-2

Model claim: Promote calcium absorption.Supports bone health

「この食品はカルシウムを豊富に含みます。日頃の運動と適切な量のカルシウムを含む健康的な食事は、若い女性が健全な骨の健康を維持し、歳をとってからの骨粗鬆症になるリスクを低減するかもしれません。」

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“Daily exercise and healthy diet containing adequate dose of calcium maintain bone health and may reduce risk of osteoporosis in the elderly age.”

Example 3-3

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Disease Risk Reduction Claim

• Evidences must be based on the comprehensive and intensive researches of published scientific papers and results from published meta-analysisare also submitted.

• Disease risk reduction claims should be are strongly related to the domestic nutritional circumstances

• Applications of Disease risk reduction claims and FOSHU must be simultaneously done

Notification Shokuanhatsu 0201003, 2007 Feb.1 21

Recognized Disease Risk Reduction Claims of FOSHU

Disease risk reduction claims are permitted to FOSHU products with conditions shown below. Permission of claiming disease risk reduction are limited to calcium and folic acid.

Calcium：Daily intake of calcium from FOSHU products should be included between 300mg and 700 mg

Claim：This product contains calcium in abundance. Intake of appropriate amount of calcium contained in healthy meals with appropriate exercise supports health of bones of young women and may reduce the risk of osteoporosis when aged.

13/967 (as of 13 Oct 2011)

Folic Acid：

Daily intake of folic acid from FOSHU products should be included between 400㎍and 1,000㎍

Claim：This product contains folic acid abundance. Healthy meals containing appropriate amount of folic acid may supports women to bear healthy baby by reduction of risk of neural tube defect such as spondyloschisis.

0/967 (as of 13 Oct 2011)

Calcium

Folic acid

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Various categorical terms have no legal basis

Legal base

1) Food for Specified Health Uses (FOSHU, 特定保健用食品);

2) Food with Nutrient Functional Claims（FNFC, 栄養機能食品);

3) Food for Special Dietary Uses (FOSDU,特別用途食品)

No legal base

health food (健康食品), health supplementary food (健康補助食品), nutritional supplementary food(栄養補助食品), nutritional strengthened food(栄養強化食品), nutritional regulating food(栄養調整食品), health drink(健康飲料）, “sapurimento”(サプリメント）

Rich vocabulary !But problem in Japan is that market of so-called “health food” isso large.

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PICO in EBM: defining problem

Patient : young female

Intervention: calcium rich food

Control : non-treatment

Outcome : bone density or fracture

“prevention of osteoporosis”

risk reduction of disease

In Japan• In risk reduction health claim, word is

simple and easy to understand. Poor vocabulary.

• But in “structure and function claim” in so-called health foods, there are lots of words, which is difficult to understand. Rich vocabulary.

• Why ?

• Problems in regulation in “structure andfunction claim”

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Japanese Pharmaceutical Affairs Law (1961)

(Definitions)Article 2 The term “drug” used in this law refers to the

articles specified in the following items.(1) the article recognized in the Japanese Pharmacopeia.(2) The article (excluding quasi-drugs) which is intended

for use in the diagnosis, treatment, or prevention of disease in humans or animals, and which is not equipment/instrument (including dental materials, medical or sanitary supplies; the same herein after)

(3) The article (excluding quasi-drugs and cosmetics) which is intended to affect the structure or functions of the human or animal body, and which is not equipment/instrument etc.

From website of National Institute of Health and Nutrition

「健康食品」は、医薬品ではありませんので、医薬品のような疾病の治療・予防等を目的とする表示や、身体の構造や機能に影響を及ぼすことを目的とする表示は、医薬品的な効能効果とされ、表示することができません。しかしながら、以下に述べる国の制度「保健機能食品」については、「お腹の調子を整える」、「食後の血糖値の上昇を抑える」、「カルシウムは、骨や歯の形成に必要な栄養素です」といった身体の構造や機能に影響を及ぼすことを目的とする表示を行って販売することが可能となっています。

Because that “health food” is not drug, it can not have health claim with aim of treatment, prevention and others; nor affect structure and function of the body. However, ... FOSHU and FNFC can do it.

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US Federal Food, Drug and Cosmetic Act (FD&C Act)

SEC. 201. [21. U.S.C. 321]

The term “drug” means

(A) Articles recognized in USP, others

(B) Articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease...

(C) Articles (other than food) intended to affect the structure or any function of the body...

(D) …

Japanese Pharmaceutical Affairs Law (1948)

(Definitions)Article 2 The term “drug” used in this law refers to the

articles specified in the following items. But excludes equipment.

(1)… (almost same as 1961 law) (2)… (almost same as 1961 law)(3) The article (excluding food) which is intended to

affect the structure or functions of the human or animal body

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Clinical trial on each “product”

or

Systematic review on food or ingredient

In the US, systematic review has been used for assessment of food and ingredient for SSA and QHC by FDA.

In EU, systematic review has been used for assessment of food supplement by EFSA.

In Japan, systematic review has been used for certain field of drugs, and is being used in certain field of food by regulatory agency.

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平成9 (1997)年度厚生科学研究オーファンドラッグ開発研究事業

「難治疾患・稀少疾患に対する医薬品の適応外使用のエビデンスに関する調査研究」

班長：津谷喜一郎

報告書 平成10(1998)年4月33

FY 1997 MHW funded project“Study on the evidence of off-label use of

drugs for intractable or rare diseases”Chair: Kiichiro Tsutani

Report published in April 1998

Application on the base of “publicly known evidence”

(公知申請）

• Not based on individual clinical trial• But based on systematic review of all

study world wide.

• Notification 1 February 1999

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適応外使用に係る医療用医薬品の取扱いについて研究開発振興課長・審査管理課長（1999.2.1）

(1) 外国(本邦と同等の水準にあると認められる承認の制度又はこれに相当する制度を有している国(例えば、米国)をいう。以下同じ。)において、既に当該効能又は効果等により承認され、医療における相当の使用実績があり、その審査当局に対する承認申請に添付されている資料が入手できる場合

(2) 外国において、既に当該効能又は効果等により承認され、医療における相当の使用実績があり、国際的に信頼できる学術雑誌に掲載された科学的根拠となり得る論文又は国際機関で評価された総説等がある場合

(3) 公的な研究事業の委託研究等により実施されるなどその実施に係る倫理性、科学性及び信頼性が確認し得る臨床試験の試験成績がある場合

・・・、最近の厚生科学研究においてその科学的根拠の評価が実施されているところである。・・・次に掲げる場合であって・・・

1999 2004

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MHLW funded project “Evidence of Food for Special Dietary Uses” (FOSDU) Report in Mar 2009

First systematic review used in “health food” in Japan

Low protein foodAllergen removed foodNon lactose foodThick liquid foodModified food for infantFood for dysphagia

Germinated Barley Foodstuff (GBF)Low protein milk (L.P.K)Fine RiceOS 1

Table 5-1 特別用途食品のエビデンステーブル 2008

18,134 277 37 330 51 1,086 16,271 36 0 0 1 0 21 18 - 2 4

(43) (14) (2*) (3) (1) (13) (2) (4) (0) (0) (0) (0) (2) (0) (-) (1) (1)

1,330 78 42 53 7 373 610 100 0 1 13 1 10 42 - - -

(25) (2) (0) (3) (1) (15) (-) (2) (0) (1) (1) (0) (0) (0) (-) (-) (-)

439 30 37 8 3 188 93 79 0 1 0 0 0 0 - - -

(21) (5) (0) (2) (1) (10) (-) (2) (0) (1) (0) (0) (0) (0) (-) (-) (-)

2,731 68 36 70 14 621 1,782 67 0 0 11 5 10 46 - 1 -

(15) (1) (0) (2) (6) (-) (-) (0) (0) (0) (5) (0) (0) (0) (-) (1) (-)

427 81 148 0 0 6 6 127 0 0 8 0 5 0 31 1 14

(32) (0) (0) (0) (0) (6) (0) (11) (0) (0) (3) (0) (0) (0) (8) (1) (3)0 37 0 0 2 6 32 0 0 1 0 1 0 11 - -

(0) (0) (0) (0) (2) (0) (1) (0) (0) (0) (0) (0) (0) (0) (-) (-)

3 37 0 0 0 0 21 0 0 0 0 0 0 7 - -

(0) (0) (0) (0) (0) (0) (8) (0) (0) (0) (0) (0) (0) (7) (-) (-)

1 37 0 0 0 0 32 0 0 0 0 0 0 1 - -

(0) (0) (0) (0) (0) (0) (2) (0) (0) (0) (0) (0) (0) (1) (-) (-)

77 37 0 0 4 0 42 0 0 7 0 4 0 12 1 14

(0) (0) (0) (0) (4) (0) (0) (0) (0) (3) (0) (0) (0) (0) (1) (3)

3,639 126 37 142 36 2,446 473 57 5 8 13 1 9 210 - 2 74

(49) (6) (0) (23) (12) (-) (-) (1) (2) (2) (2) (0) (-) (-) (-) (翻訳 1) （-）

438 79 36 53 3 60 49 36 0 0 3 1 5 112 - - 1

(18) (4) (0) (4) (1) (5) (-) (3) (0) (0) (0) (0) (0) (0) (-) (-) (1)

27,138 739 373 656 114 4,780 19,284 502 5 10 49 8 60 428 31 6 93

(203) (32) (2) (37) (22) (49) (2) (23) (2) (4) (11) (0) (2) (0) (8) (4) (5)

- ：実施せず。

（ ） ：（ ）内は構造化抄録数。

* ：DARE由来のため、構造化抄録コード番号はDARE側のものとした。

（-） ：スクリーニング対象とせず。

それぞれの詳細は本文参照

no. 新カテゴリー 検索結果NGC

(E1 )

NLH

(E2 )

The Coch ran e Library

MEDLINE

(E6)

東邦大学医学

メディアセンター

(J1 )

医中誌各企業への文

献請求

(M1)

班メンバーか

らの提供資料

(M2)

参考文献から

の2 次資料

(M3)CDSR

(E3 )

DARE

(E4 )

CENTRAL

(E5 )

CPG

(J2 )

META

(J3 )

RCT

(J4 )

準RCT

(J5 )

臨床試験

(J6 )

比較研究

(J7 )

1 低たんぱく質食品

2 アレルゲン除去食品

3 無乳糖食品

4総合栄養食品

（いわゆる濃厚流動食）

5 個別評価型食品

a) 発芽大麦

GBF(3)

b) 低リンミルク

　　L.P.K(15)

c) ファインライス

(3)

d) オーエスワン

(11)

6 乳児用調製粉乳

7 えん下困難者用食品

Total

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40

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What is label/claim easy to understand for consumer (draft)

第２回食品表示一元化検討会資料 2011.10.25

Summary and proposed action

• Too many words in health food in Japan. Rich vocabulary ⇒ to be streamlined

“Poor vocabulary is better”

• Public’s perception study to be conducted

• Development of negative list of misleading terminology of so-called health food

• Establishment of comprehensive law specifying all health food in Japan, including revision of pharmaceutical affairs law. 44

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Acknowledgements

• Dr. Dae Seog HEO, Seoul National University College of Medicine;

NECA

• Dr. Hirobumi OHAMA, Japanese Institute for Health Food Standards (JIHFS)

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Thank you

ご清聴ありがとうございました