commission on dietary supplement labels november

COMMISSION ON DIETARY SUPPLEMENT LABELSNovember 1997

COMMISSION ON DIETARY SUPPLEMENT LABELSNovember 1997

MEMBERSHIP OF THE COMMISSION ON DIETARY SUPPLEMENT LABELS

Chair

Malden C. Nesheim, Ph.D.Provost Emeritus

Professor of NutritionCornell UniversityIthaca, New York

Annette Dickinson, Ph.D. Shiriki K. Kumanyika, Ph.D., M.P.H.Director, Scientific and Regulatory AffairsCouncil for Responsible NutritionWashington, DC

Norman R. Farnsworth, Ph.D.Research Professor of Pharmacognosy and Senior University ScholarCollege of PharmacyThe University of Illinois at ChicagoChicago, Illinois

Margaret Gilhooley, L.L.B. Podesta AssociatesProfessorSeton Hall University School of LawNewark, New Jersey

Professor and Head, Department of Human Nutrition and DieteticsThe University of Illinois at ChicagoChicago, Illinois

Robert S. McCalebPresidentHerb Research FoundationBoulder, Colorado

Anthony PodestaPresident

Washington, DC

Staff

Kenneth D. Fisher, Ph.D. Linda D. Meyers, Ph.D.Executive Director Deputy Director

C. Elizabeth Castro, Ph.D.Senior Research Fellow

Kathryn Y. McMurry, M.S.Nutrition and Food Science Advisor

Senior Nutrition Advisor

Sandra SaundersSecretary

Address

Office of Disease Prevention and Health PromotionHubert H. Humphrey Building

Room 738G 200 Independence Ave., SW

Washington, DC 20201

COMMISSION ON DIETARY SUPPLEMENT LABELS

November 24, 1997

The PresidentThe White HouseWashington, D.C. 20500

Dear Mr. President:

On behalf of the Commission on Dietary Supplement Labels, I am pleased to transmit the finalreport of the Commission. The seven-member Commission, which you appointed, examineda number of issues associated with labeling of dietary supplements, as set forth in the DietarySupplement Health and Education Act of 1994. This report completes the duties of theCommission as assigned in its charter of February 1996.

As requested, the Commission conducted a study on and is providing recommendations for theregulation of label claims and statements for dietary supplements, including the use of literaturein connection with the sale of dietary supplements and procedures for the evaluation of suchclaims. To accomplish its task, the Commission obtained advice from individuals, consumerorganizations, the dietary supplement industry, and scientific organizations through writtensubmissions and a series of public meetings throughout the United States. A preliminary reportwas released for public comment in June 1997. This final report reflects the consideration ofmaterials, documents, and opinions submitted to the Commission during its deliberations.

The report contains the Commission's recommendations for regulations and provides guidanceto government agencies and the dietary supplement industry relative to safety, label statements,health claims, substantiation of claims, and botanical supplements. The report emphasizes theneed for public access to the evidence on which label statements are based so that consumerscan make informed decisions about the use of dietary supplements.

Although the Commission operated independently from any policy guidance from the Depart-ment of Health and Human Services, we are grateful for the logistic and staff support providedby the Department through the Office of Disease Prevention and Health Promotion. We alsowish to acknowledge the assistance of dedicated and able staff. We believe our report makesvaluable recommendations and provides guidance that will be of benefit to consumers and thesupplement industry.

Sincerely,

Malden C. Nesheim, Ph.D.Chairman


November 24, 1997

The Honorable Albert Gore, Jr.President of the SenateWashington, D.C. 20510

Dear Mr. President:

On behalf of the Commission on Dietary Supplement Labels, I am pleased to transmit the finalreport of the Commission. The seven-member Commission appointed by President Clintonexamined a number of issues associated with labeling of dietary supplements, as set forth in theDietary Supplement Health and Education Act of 1994. This report completes the duties of theCommission as assigned in its charter of February 1996.




Sincerely,

Malden C. Nesheim, Ph.D.Chairman


November 24, 1997

The Honorable Newt GingrichSpeaker of the House of RepresentativesWashington, D.C. 20515

Dear Mr. Speaker: On behalf of the Commission on Dietary Supplement Labels, I am pleased to transmit the finalreport of the Commission. The seven-member Commission appointed by President Clintonexamined a number of issues associated with labeling of dietary supplements, as set forth in theDietary Supplement Health and Education Act of 1994. This report completes the duties of theCommission as assigned in its charter of February 1996.




Sincerely,

Malden C. Nesheim, Ph.D. Chairman


November 24, 1997

The Honorable Donna ShalalaSecretary of Health and Human ServicesWashington, D.C. 20201

Dear Madam Secretary:

On behalf of the Commission on Dietary Supplement Labels, I am pleased to transmit the finalreport of the Commission. The seven-member Commission appointed by President Clintonexamined a number of issues associated with labeling of dietary supplements, as set forth in theDietary Supplement Health and Education Act of 1994. This report completes the duties of theCommission as assigned in its charter of February 1996.




Sincerely,

Malden C. Nesheim, Ph.D. Chairman

Commission on Dietary Supplement Labels iii

Table of Contents

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v

Chapter I: DIETARY SUPPLEMENT HEALTH AND EDUCATION ACT OF 1994 . . . . . . 1

Major Provisions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1The Commission on Dietary Supplement Labels . . . . . . . . . . . . . . . . . . . 5Endnote . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Chapter II: BACKGROUND ON DIETARY SUPPLEMENTS . . . . . . . . . . . . . . . . . . . . . 11

Pertinent Legislation and Regulations . . . . . . . . . . . . . . . . . . . . . . . . . . 11Consumer Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Characteristics of The U.S. Dietary Supplement Industry . . . . . . . . . . . 17

Chapter III: MAJOR ISSUES AND RECOMMENDATIONS RELATED TO LABELING

OF DIETARY SUPPLEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Safety of Dietary Supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Label Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26NLEA Claims in Dietary Supplement Labeling . . . . . . . . . . . . . . . . . . . 29Scope of Statements of Nutritional Support . . . . . . . . . . . . . . . . . . . . . 35Notification Letters for Statements of Nutritional Support . . . . . . . . . . 39Substantiation Files for Statements of Nutritional Support . . . . . . . . . . . 42Publications Exempt From Classification as Labeling When

Used in Connection With Sales . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45Botanical Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48Endnotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

Chapter IV: ADDITIONAL ISSUES AND RECOMMENDATIONS IDENTIFIED BY THE

COMMISSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

Information for Consumers and Health Professionals . . . . . . . . . . . . . . . 59Need for Industry Expert Advice on Safety, Label Statements, and

Claims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64Research Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65NIH Office of Dietary Supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

Chapter V: LITERATURE CITED . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

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iv Commission on Dietary Supplement Labels

Appendix A: DIETARY SUPPLEMENT HEALTH AND EDUCATION

ACT OF 1994 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A-1

Appendix B: CHARTER OF THE COMMISSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B-1

Appendix C: COMMISSION PROCEDURES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C-1

Appendix D: INDIVIDUALS AND ORGANIZATIONS PRESENTING ORAL

TESTIMONY TO THE COMMISSION . . . . . . . . . . . . . . . . . . . . . . . . D-1

Appendix E: INDIVIDUALS AND ORGANIZATIONS PROVIDING WRITTEN

SUBMISSIONS TO THE COMMISSION . . . . . . . . . . . . . . . . . . . . . . . E-1

Appendix F: ACRONYMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . F-1

Table 1: REGULATIONS RELATED TO DIETARY SUPPLEMENTS

SINCE PASSAGE OF DSHEA . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Table 2: STATUS OF HEALTH CLAIMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Table 3: EXAMPLES OF DISCLAIMERS USED IN OTHER COUNTRIES . . . . . . . . . . . 53

Table 4: FY 1995 EXPENDITURES AND NUMBER OF PROJECTS IN HUMAN

NUTRITION RESEARCH, MANPOWER DEVELOPMENT, TRAINING, AND EDUCATION BY FEDERAL AGENCIES . . . . . . . . . . . . . . . . . . . . 67

Table 5: OBLIGATIONS FOR NUTRITION RESEARCH AND TRAINING BY

AGENCY, FISCAL YEARS 1986 THROUGH 1995(THOUSANDS OF DOLLARS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

Figure 1: CHRONOLOGY: OCTOBER 1994 TO NOVEMBER 1997 . . . . . . . . . . . . . . . 8

Figure 2: ECHINACEAE PURPUREAE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Figure 3: RHIZOMA ZINGIBERIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

Commission on Dietary Supplement Labels v

Executive Summary

The Dietary Supplement Health andEducation Act (DSHEA or the Act) of 1994was enacted by Congress following publicdebate concerning the importance of dietarysupplements in leading a healthy life, theneed for consumers to have current andaccurate information about supplements, andcontroversy over the Food and DrugAdministration (FDA) regulatory ap-proach to dietary supplements. PresidentClinton, in signing the legislation into law onOctober 25, 1994, said:

After several years of intense efforts,manufacturers, experts in nutrition, andlegislators, acting in a conscientiousalliance with consumers at thegrassroots level, have moved success-fully to bring common sense to thetreatment of dietary supplements underregulation and law.

This legislation defines dietary supplements,places the responsibility for ensuring theirsafety on manufacturers, identifies howliterature may be used in connection withsales, specifies types of statements ofnutritional support that may be made onlabels, specifies certain labeling require-ments, and provides for the establishment ofregulations for good manufacturing prac-tices. The legislation creates an Office ofDietary Supplements (ODS) in the NationalInstitutes of Health (NIH), with a mandateto coordinate scientific research relating todietary supplements within NIH and toadvise Federal agencies on issues relating todietary supplements.

DSHEA also directs the President to appointa Commission on Dietary Supplement Labelsto consider several issues needingclarification when the Act was passed. TheAct indicates that the Commission is to:

. . . conduct a study on, and providerecommendations for, the regulation oflabel claims and statements for dietarysupplements, including the use ofliterature in connection with the sale ofdietary supplements and procedures forthe evaluation of such claims.

In making its recommendations, theCommission is to:

. . . evaluate how best to providetruthful, scientifically valid, and notmisleading information to consumers sothat such consumers may makeinformed and appropriate health carechoices for themselves and theirfamilies.

A seven-member Commission was appointedby President Clinton in October 1995, and itscharter was approved by the Secretary of theDepartment of Health and Human Services(HHS) on February 13, 1996. TheCommission convened its first meeting inFebruary 1996. In the course of itsdeliberations, the Commission held publicmeetings at several sites around the UnitedStates and received oral and writtentestimony from interested organizations andindividuals who presented views on issuesrelated to the Commission’s charge.

Reflecting the charge to the Commission inDSHEA and in the Commission’s charter,this report is addressed to the President,Congress, and the Secretary of HHS. Theorganization of the report is as follows:

! Chapter I summarizes the major pro-visions of DSHEA and the charge to theCommission.

! Chapter II reviews the legislative and

regulatory context surrounding DSHEAand summarizes information related to

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vi Commission on Dietary Supplement Labels

consumer use of dietary supplements and safety, health claims, statements of nutri-the supplement industry. tional support, notification letters, substanti-

! Chapters III and IV present findings, with sales, and some special considerationsguidance, and recommendations related regarding botanical products. The Commis-to the key issues identified by the sion also addressed consumer and healthCommission during its deliberations. The professional information needs; industryconclusions of the Commission are expert advice on safety, label statements, andpresented in each section of these two claims; research issues; and the Office ofchapters in this manner (See Executive Dietary Supplements.Summary Endnote 1):

FINDINGS are the conclusionsreached by the Commission duringits deliberations and are based on theinformation and data received andreviewed by the Commission.

GUIDANCE represents advice tospecific agencies, groups, or individ-uals. Guidance should be consideredby the identified recipients as theydevelop or implement activities re-lated to the availability of dietarysupplements in the marketplace.

RECOMMENDATIONS are indicatedas such and identify the intendedrecipients. Recommendations thatcall for consideration of changes inexisting regulations, development ofnew regulations, or legislative actionare so indicated.

The Commission on Dietary SupplementLabels was aware of the public interest in itswork and desired to have an additionalpublic comment period. Therefore, a draftreport was released for public comment onJune 24, 1997.

This executive summary highlights thefindings, guidance, and recommendationsmade by the Commission in the areas of

ation files, publications used in connection

SAFETY OF DIETARYSUPPLEMENTS

The Commission considers it axiomatic thatall marketed dietary supplements should besafe. Congress, in reflecting on the issuesassociated with safety, concludes in DSHEAthat dietary supplements “are safe within abroad range of intake, and safety problemswith the supplements are relatively rare.”Congress emphasizes in the Act that thegovernment should take swift action whensafety problems arise but should not imposeunreasonable barriers or limit access to safeproducts.

GUIDANCE

Manufacturers and the industry as a wholemust fully accept the responsibility forassuring the safety of dietary supplementsand must take any action necessary to meetthe expectation expressed in DSHEA thatdietary supplements are and will continue tobe safe for use by the consuming public.

! The Commission urges FDA, theindustry, the scientific community, andconsumer groups to work togethervoluntarily to improve passive postmar-keting surveillance systems, includingadverse reaction reporting systems, toensure that any safety problems thatmay arise are identified and correctedpromptly.

Executive Summary

Commission on Dietary Supplement Labels vii

! Ensuring the safety of supplementsincludes the need to provide adequateinformation and warnings to consumers.The Commission strongly suggests thatdietary supplement manufacturersinclude appropriate warnings in productinformation where necessary, as spe-cifically permitted by DSHEA. In addi-tion, manufacturers should recognizethe need to advise women who arepregnant or breast-feeding to consult ahealth professional about supplementuse during the pre- and postnatalperiods.

! The Commission urges FDA to use itsauthority under DSHEA to take swiftenforcement action to address potentialsafety issues such as those posedrecently by products containing ephed-rine alkaloids. While it is expected thata responsible industry will avoid market-ing unsafe products and that theindustry will react promptly to removeproducts shown to be associated withsignificant or serious adverse reactions,in the final analysis there must be astrong and reliable enforcement systemto back up the safety provisions ofDSHEA. Failure by FDA to act whenstrong enforcement is needed under-mines public confidence in the ability ofnot only the Federal government butalso the dietary supplement industry toensure safety and avoid harm to thepublic.

! FDA and, within many states, certainagencies have the responsibility inenforcement actions to develop, affir-matively, the evidence that shows anunreasonable risk from using existingsupplements. FDA and appropriateagencies in some States may needadditional resources to develop thenecessary evidence, and these agenciesneed to be given the resourcesnecessary to meet this importantresponsibility in the context of theiroverall public health priorities.

NLEA CLAIMS IN DIETARYSUPPLEMENT LABELING

In enacting DSHEA, Congress implicitlyintended the Commission to determinewhether any changes should be made in therequirements for health claims allowed bythe Nutrition Labeling and Education Act of1990 (NLEA) for dietary supplements.Current FDA rules require the same type ofscientific evidence and support and the sameprocess for approval of NLEA health claimson dietary supplements as are required forconventional foods.

GUIDANCE

! The process for approval of healthclaims as defined by NLEA shouldremain the same for dietary supple-ments and conventional foods.

! The standard of significant scientificagreement is appropriate and serves thepublic interest. The standard ofsignificant agreement should not be sostrictly interpreted as to requireunanimous or near-unanimous support.

! FDA should ensure that broad input isobtained to ascertain the degree ofscientific agreement that exists for aparticular health claim. The use ofappropriate panels of qualified scientistsfrom outside of the agency is encour-aged, and the views of other govern-ment agencies should be given con-siderable weight in determining whethersignificant scientific agreement exists.

SCOPE OF STATEMENTS OFNUTRITIONAL SUPPORT

DSHEA allows dietary supplement labelingto bear statements of nutritional supportwithout preauthorization by FDA. FDA hasreceived notification letters regarding more

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viii Commission on Dietary Supplement Labels

than 1,000 such statements. Review of theletters and consideration of testimonypresented to the Commission indicate thatclarification of the scope of a nutritionalsupport statement may be helpful tomanufacturers.

GUIDANCE

! While the Commission recognizes thatthe context of a claim has to be con-sidered on a case-by-case basis, theCommission proposes the followinggeneral guidelines:

1. Statements of nutritional supportshould provide useful information toconsumers about the intended useof a product.

2. Statements of nutritional supportshould be supported by scientificallyvalid evidence substantiating thatthe statements are truthful and notmisleading.

3. Statements indicating the role of anutrient or dietary ingredient inaffecting the structure or function ofhumans may be made when thestatements do not suggest diseaseprevention or treatment.

4. Statements that mention a bodysystem, organ, or function affectedby the supplement using terms suchas “stimulate,” “maintain,” “support,”“regulate,” or “promote” can beappropriate when the statements donot suggest disease prevention ortreatment or use for a serious healthcondition that is beyond the ability ofthe consumer to evaluate.

5. Statements should not be made forproducts to “restore” normal or“correct” abnormal function whenthe abnormality implies the presenceof disease. An example might be aclaim to “restore” normal blood

pressure when the abnormalityimplies hypertension.

6. Health claims are specificallydefined under NLEA as statementsthat characterize the relationshipbetween a nutrient or a foodcomponent and a specific disease orhealth-related condition. Statementsof nutritional support should bedistinct from NLEA health claims inthat they do not state or imply a linkbetween a supplement andprevention of a specific disease orhealth-related condition.

7. Statements of nutritional support arenot to be drug claims. They shouldnot refer to specific diseases,disorders, or classes of diseasesand should not use drug-relatedterms such as “diagnose,” “treat,”“prevent,” “cure,” or “mitigate.”

! To the extent resources permit, FDAshould continue to provide guidance tomanufacturers by responding to lettersof notification when the agency deems aproposed statement to be inappropriateas a statement of nutritional support.

NOTIFICATION LETTERS FORSTATEMENTS OF NUTRITIONALSUPPORT

DSHEA requires that the manufacturer of adietary supplement bearing a statement ofnutritional support notify the Secretary nolater than 30 days after the first marketing ofthe dietary supplement that such a statementis being made. The law also states that themanufacturer must have substantiation thatsuch a statement is truthful and notmisleading. The law does not provide thatthe evidence supporting a statement bereviewed by a regulatory agency prior tomarketing of the product. The Commission

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Commission on Dietary Supplement Labels ix

agreed that guidelines are needed forstandardizing the format and content of thenotification letters.

GUIDANCE

! Notification letters should continue to beavailable in the public dockets.

! While the rulemaking process need notbe reopened at this time, the Commis-sion suggests that notification lettersshould include the following information:

1. A statement that the purpose of theletter is to provide notification of astatement of nutritional support,including the exact wording thatappears on the product label.

2. The name, address, and telephonenumber of the manufacturer ordistributor, and if available, theaddress and/or toll-free telephonenumber for consumer inquiries.

3. The name and description of theproduct. The name of the productshould include the trade name andthe common or usual name. A copyof the product label or label copy, iflabels are not yet printed, should be stances, qualified statements based solely onincluded.

4. The identity of specific individualingredients or combinations ofingredients for which the statementof nutritional support is made. Forbotanicals, ingredients should beidentified by the common or usualname, the Latin binomial and itsscientific authority, and the part(s) ofthe plant(s) used.

5. A statement of intended use,including the recommended dosageand appropriate contraindications orwarnings.

! In the notification letter or in a separatepublic notice manufacturers shouldprovide statements of affirmation thatthey have substantiation for thestatement of nutritional support and thatthe product does not represent asignificant or unreasonable risk of illnessunder conditions of use recommendedor suggested in labeling.

! Although some of the informationindicated in the above guidelines is notrequired by FDA, the Commissionsuggests that manufacturers use theseguidelines in preparing their notificationletters.

SUBSTANTIATION FILES FORSTATEMENTS OF NUTRITIONALSUPPORT

The Commission discussed how a statementof nutritional support can be adequatelysubstantiated when it is based solely onhistorical use without supporting experi-mental or clinical data. At a minimum, sucha statement of nutritional support wouldhave to be carefully qualified to preventmisleading consumers. Some Commissionmembers believe that, in some circum-

historical use would be recognized byexperts as being adequately substantiated.Other Commissioners believe that expertswould want more scientific support forsubstantiation and especially so in the case ofstatements that have particular healthimportance. One Commissioner believesthat scientific support for substantiation isneeded for all statements with healthimportance.

DSHEA does not require that substantiationfiles be made available to FDA, and themajority of the Commission members are notrecommending a change in legislationregarding the availability of these files.

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x Commission on Dietary Supplement Labels

However, one member believes that FDAneeds to be able to obtain access to therelevant files of a manufacturer to enforceeffectively the manufacturer’s obligation tosubstantiate statements of nutritional supportand the obligation to substantiate safety.That member believes the authority to obtainaccess to substantiation files should beprovided either through a rule similar to thatproposed by FDA on nutrient contentclaims based on new technology for foodingredients or through legislative action.

The Commission provides the followingguidance regarding the information aresponsible manufacturer should have in asubstantiation file for a statement ofnutritional support and product safety. Whilethe Commission’s guidance on substantiationfiles is directed to statements of nutritionalsupport and safety, other types of labelstatements may be made for dietarysupplements. The Commission’s guidance onsubstantiation file content may also behelpful in identifying what a responsiblemanufacturer would do for substantiation ofother types of label statements.

GUIDANCE

! Substantiation files for statements ofnutritional support and safety shouldinclude the following information:

1. A copy of the notification letter.

2. The identity and quantity of thedietary ingredient(s) that is (are) thesubject of the statement of nutri-tional support.

3. The key evidence to substantiatestatements of nutritional support,including an interpretive summary ofthe evidence by an individual(s) orgroup qualified by training andexperience.

4. Evidence substantiating the safety ofthe product.

5. Assurance that good manufacturingpractices were followed in themanufacture of the product.

6. The qualifications of the individual(s)or group who reviewed the evidencefor safety and efficacy.

PUBLICATIONS EXEMPT FROMCLASSIFICATION AS LABELINGWHEN USED IN CONNECTIONWITH SALES

DSHEA directs the Commission to studyand make recommendations on theregulation and evaluation of the use ofliterature in connection with the sale ofdietary supplements. DSHEA exemptspublications used in connection with the saleof dietary supplements from being defined aslabeling under certain conditions.

The Commission finds that the requirementsof Section 5 of DSHEA may be difficult toapply, especially the requirement that anarticle provide (or be displayed with otherpublications that provide) a balanced view ofthe available information. Although thisprovision of DSHEA seems to have beenwritten with scientific articles in mind, theterm publication has a broader meaning.Also, the Commission recognizes thatscientific articles may not be consumerfriendly. Therefore, it appears likely that thebulk of the literature used in accordance withthis provision may be in the form ofpublications specifically prepared for thispurpose and written for the consumer.

GUIDANCE

Executive Summary

Commission on Dietary Supplement Labels xi

! Because more experience with theimplementation of this provision mayprovide additional information about theuse of publications in connection with asale, the Commission suggests thatproactive monitoring of practice in thisarea be undertaken by FDA asresources permit and that regulatoryguidance be developed if necessary.

BOTANICAL PRODUCTS

Botanical products represent a majorcategory of dietary supplements. TheCommission observes that many botanicalproducts sold as dietary supplements areused for prevention or treatment purposes.The scientists on the Commission noted that,in some cases, there is current scientificevidence to support such use. Most Com-missioners believe that, in some cases, theconsumer would be better served by clearinformation regarding preventive and thera-peutic uses than by the limited statements ofnutritional support permitted by DSHEA.

The Commission believes it would be logicaland desirable for the U.S. over-the-counter(OTC) drug system to include preventive ortherapeutic claims for botanicals, at least forthose having a long history of use andgeneral recognition of safety and efficacybased on adequate studies. The Commissionalso recognizes that there are botanicalproducts used as remedies by some segmentsof the U.S. population that may not meetstandards of evidence needed for OTCapproval. In many other industrializedcountries in the world, claims for botanicalremedies and medicines are permitted, oftenwith specific disclaimers, as a uniquecategory of nonprescription products withinthe drug regulatory system. The types ofdisclaimers that are used and that may beneeded are described in this report. Theappropriate regulation of these products as

remedies was considered to be outside of theCommission’s charge and expertise butdeserving of further study.

GUIDANCE

! More study is needed regarding theestablishment of some alternativesystem for regulating botanical productsthat are used for purposes other than tosupplement the diet, but that cannotmeet OTC drug requirements. The studyshould include the types of disclaimersthat might apply and theappropriateness of such a system withinthe U.S. regulatory framework. Such acomprehensive study would go beyondthe mandate of this Commission, whichis limited to dietary supplement uses ofthese products.

! The Commission concluded that acomprehensive evaluation of regulatorysystems used in other countries forbotanical remedies is needed. Such anevaluation should consider the scope ofproducts covered, the means of assur-ing safety and preventing deception, theeffect of such systems on overallmedical care, the definition of appro-priate drug uses of products, and theappropriateness and applicability of thedifferent types of disclaimers.

RECOMMENDATIONS

! The Commission recognizes that, underDSHEA, botanical products shouldcontinue to be marketed as dietarysupplements when properly labeled.

! The Commission strongly recommendsthat FDA promptly establish a reviewpanel for OTC claims for botanicalproducts that are proposed by manu-facturers for drug uses. The panelshould have appropriate representationof experts on such products.

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xii Commission on Dietary Supplement Labels

INFORMATION FOR CONSUMERSAND HEALTH PROFESSIONALS

DSHEA charged the Commission todetermine how best to provide truthful,scientifically valid, and not misleadinginformation to consumers so that they maymake informed and appropriate health carechoices for themselves and their families.The Commission believes additional researchis needed on the type of label informationthat would be most useful to consumers.Other avenues of consumer information,including advice from health professionals,could be critical in assisting consumers inmaking appropriate decisions relative tosupplement use.

GUIDANCE

! The Commission urges that dietary increased level of scientific input intosupplement labeling be evaluated inadditional consumer research todetermine whether consumers actuallywant and can utilize the informationrequired by existing FDA regulations, bythe requirements of DSHEA, and in therecommendations of this Commission.The Commission recognizes that con-sumer understanding of statements ofnutritional support and health claims, aswell as consumer perception of dietarysupplement use based on literature atthe point of sale, are important aspectsof the use of information that requireadditional and continued assessment.

! The Commission believes that it isimportant for health and nutritionprofessionals to become more know-ledgeable about all types of dietarysupplements and to assist the consumerin making appropriate health carechoices with respect to use of dietarysupplements.

! The Commission urges manufacturersto make available publicly balanced and

nonmisleading summaries of the evi-dence substantiating statements ofnutritional support and product safety forthe intended use at the stated dosage.The summary should not claim use forprevention or treatment of disease.

NEED FOR INDUSTRY EXPERTADVICE ON SAFETY, LABELSTATEMENTS, AND CLAIMS

Dietary supplements are eligible for a varietyof label statements and claims, each of whichhas unique regulatory requirements. Despitethe diverse regulatory provisions, in apractical sense, the messages conveyed toconsumers by label statements of nutritionalsupport, NLEA health claims, and OTC drugclaims may be similar. The Commissionbelieves that the dietary supplement industryand consumers would benefit from an

decisions regarding label statements fordietary supplements. An expert advisorypanel on dietary supplements could be avaluable source of increased scientific input.

GUIDANCE

! The Commission recommends that thedietary supplement industry considerestablishing an expert advisory commit-tee on dietary supplements to providescientific review of label statements andclaims and to provide guidance to theindustry regarding the safety, benefit,and appropriate labeling of specificproducts. Such a committee might besupported by one or more industry tradeassociations or might be established asan independent entity funded byextramural grants and/or fees forservices.

RESEARCH ISSUES

Executive Summary

Commission on Dietary Supplement Labels xiii

DSHEA recognizes the importance ofresearch in relation to dietary supplements.In establishing ODS within NIH, Congresswished to promote the scientific study of thebenefits of dietary supplements. In con-sidering the scientific evidence for thebenefits of supplements, the Commission hasmade a number of observations relative tosupport of research on dietary supplements,the constraints to such research, and theincentives to the industry to invest inresearch in this area. The Federal govern-ment has been a major supporter of researchon the health benefits of dietary supplementsin some areas.

GUIDANCE

! The Commission believes that the publicinterest would be served by moreresearch that assesses the relationships issues . . .” relating to safety, benefits, andbetween dietary supplements andmaintenance of health and/or preventionof disease.

! Incentive mechanisms should bedeveloped to encourage the dietarysupplement industry to invest inresearch on products offered to theconsumer. FDA might consider amechanism for review of researchconducted to validate a statement ofnutritional support such that the labeldisclaimer mandated by DSHEA couldbe modified or removed. More con-sideration is needed of ways to providesufficient resources to FDA to make itpossible for the agency to take on suchan additional responsibility.

! The Commission recommends thatFederal agencies continue to supportresearch on the health benefits andsafety of dietary supplements. Re-search should be expanded beyond thetraditionally supported areas associatedwith vitamin and mineral supplementsand include research on some of the

more promising botanical products usedas dietary supplements.

NIH OFFICE OF DIETARYSUPPLEMENTS

ODS is directed by the Act to conduct andcoordinate scientific research relating todietary supplements within NIH, to coordi-nate funding for such research, to collect andcompile the results of scientific research ondietary supplements, and to compile adatabase of such research. In addition,DSHEA directs ODS to “. . . serve as theprincipal advisor to the Secretary and to theAssistant Secretary for Health and provideadvice to the Director of the NationalInstitutes of Health, the Director of theCenters for Disease Control and Prevention,and the Commissioner of Food and Drugs on

labeling of dietary supplements.

Executive Summary

xiv Commission on Dietary Supplement Labels

RECOMMENDATIONS

! ODS should strive to be an effectivefocal point for research on and under-standing of the health effects of dietarysupplements.

! ODS should place greater emphasis onits assigned role of advising othergovernment agencies on a broad rangeof issues relating to dietary supple-ments.

! Congress should fund ODS at the levelauthorized by DSHEA.

ENDNOTE

1. The conclusions reported in the Executive Summary are supported by all members of the Commission, but thereis a range of views on many of the issues discussed in the course of developing the findings, guidance, andrecommendations. Divergent views of members of the Commission are found on pages 22, 25, 34, 36, 37, 39, 41,43, 44, 47, 52, 55, 57, and 65 of the full report.

Commission on Dietary Supplement Labels 1

Chapter I

DIETARY SUPPLEMENT HEALTH AND EDUCATION ACT OF 1994

The Dietary Supplement Health andEducation Act of 1994 (DSHEA, or the Act)(Appendix A) was enacted by Congress The following provisions of DSHEA arefollowing public debate concerning the contained in the 13 sections of the Actimportance of dietary supplements in (Appendix A).promoting health, the need for consumers tohave access to current and accurate informa-tion about supplements, and controversyover the Food and Drug Administration’s(FDA) regulatory approach to this product Section 1 provides introductory informationcategory. Signing DSHEA into law on on the Act.October 25, 1994, President Clinton said:

After several years of intenseefforts, manufacturers, expertsin nutrition, and legislators,acting in a conscientiousalliance with consumers at thegrassroots level, have movedsuccessfully to bring commonsense to the treatment ofdietary supplements underregulation and law. (12)

The issues and debates that led to thepassage of DSHEA have been discussed bya number of authors (7,88,90,122-125,136).Despite extensive public debate during theconsideration of DSHEA, the officiallegislative history for the Act is limited (134)(see Chapter I Endnote).

DSHEA amends the Federal Food, Drug,and Cosmetic Act of 1938 (FDCA) to alterthe way dietary supplements are regulatedand labeled. This chapter provides anoverview of the provisions of DSHEA anddiscusses the scope of this report.

MAJOR PROVISIONS

1. Short Title, Reference, Table ofContents

2. Congressional Findings

In Section 2 of DSHEA, Congress identifies15 findings that established the rationale forDSHEA and that were meant to establish aconceptual framework for Federal regulatorypolicy regarding dietary supplements.Integral to the legislative changes wasCongress’ finding that “improving the healthstatus of United States citizens ranks at thetop of the national priorities of the Federalgovernment.”

3. Definitions

DSHEA for the first time defines dietarysupplements by law. According to Section 3of the Act, the term “dietary supplement”:

(1) means a product (other thantobacco) intended to supplement thediet that bears or contains one or moreof the following dietary ingredients:

(A) a vitamin; (B) a mineral; (C) an herb or other

botanical;(D) an amino acid;

Chapter I Dietary Supplement Health and Education Act of 1994

2 Commission on Dietary Supplement Labels

(E) a dietary supplementused by man tosupplement the dietby increasing the totaldietary intake; or

(F) a concentrate, metabolite,constituent, extract, orcombination of anyingredient described inclause (A), (B), (C), (D),or (E).

According to DSHEA, a dietary supple-ment is a product that is labeled as a dietarysupplement and is not represented for useas a conventional food or as a sole item ofa meal or the diet.

The definition describes the variety offorms—capsule, powder, softgel, gelcap,tablet, liquid, or other form—in which theseproducts can be ingested. This section ofDSHEA specifically excludes dietarysupplements from the definition of foodadditives in Section 409 of FDCA.

4. Safety of Dietary Supplements andBurden of Proof on FDA

DSHEA establishes separate standards forthe safety of dietary supplements bydescribing the conditions under whichdietary supplements are adulterated(unsafe). DSHEA applies the existing foodstandards for adulteration to dietarysupplements but requires that such adetermination be based on conditions of userecommended or suggested on the productlabel or, in the absence of suchrecommendations or suggestions, onordinary conditions of use. For new dietarysupplement ingredients (those marketedafter October 15, 1994), products may befound to be adulterated if there is inade-quate information to provide reasonable

assurance that such an ingredient does notpresent a significant or unreasonable risk ofillness or injury. In making such a deter-mination, the burden of proof rests with theFederal government.

5. Dietary Supplement Claims

Under Section 5 of DSHEA, informationabout a dietary supplement, such as “apublication, including an article, a chapterin a book, or an official abstract of a peer-reviewed scientific publication that appearsin an article and was prepared by the authoror the editors of the publication, which isreprinted in its entirety, shall not be definedas labeling when used in connection withthe sale of a dietary supplement” undercertain conditions. Such a publication maybe used in connection with the sale as longas it is truthful and not misleading; does notpromote a particular manufacturer or brandof dietary supplement; presents a balancedview or is displayed or presented with othersuch items on the same subject matter so asto present a balanced view of the availablescientific information; and does not haveappended to it any information by sticker orany other means. DSHEA also requiresthat when such third-party information isused in an establishment, it may not bedisplayed next to the supplement productbut must be physically separated from thesupplement.

6. Statements of Nutritional Support

Section 6 of DSHEA amends the NutritionLabeling and Education Act of 1990(NLEA) health claims provisions of FDCAto allow dietary supplement labels to carryany of four types of statements ofnutritional support without obtainingpremarketing authorization from FDA.



According to DSHEA, an acceptable state- DSHEA requires that, if a dietary supple-ment of nutritional support is one that: ment purports to conform to the standards

. . . claims a benefit related to aclassical nutrient deficiency anddiscloses the prevalence of suchdisease in the United States, describesthe role of a nutrient or dietaryingredient intended to affect thestructure or function of humans,characterizes the documentedmechanism by which a nutrient ordietary ingredient acts to maintainsuch structure or function, or describesgeneral well-being from consumption Recommended Value (DRV). The nutritionof a nutrient or dietary ingredient.

The legislation requires supplement manu-facturers to have substantiation of suchlabel claims and to notify FDA within 30days after first marketing a product with astatement of nutritional support that such astatement is being made. The label mustalso carry a disclaimer “prominentlydisplayed and in boldface type” that states:

This statement has not beenevaluated by the Food and DrugAdministration. This product is notintended to diagnose, treat, cure, orprevent any disease.

7. Dietary Supplement IngredientLabeling and Nutrition InformationLabeling

Section 7 of the Act imposes specificrequirements for supplement labels. Itspecifies some circumstances under whichdietary supplements would be misbranded.It provides that supplement labels must listthe name and quantity of each ingredient.In the case of a proprietary blend, the “totalquantity of all ingredients in the blend” maybe provided.

of a particular compendium, it must actuallydo so. Official compendiums identified byFDCA or Federal regulations include theU.S. Pharmacopeia (USP) and the FoodChemicals Codex. Otherwise, the identityand quality of the product must be as statedon the label.

With respect to nutrition labeling, DSHEApermits the inclusion of substances withouta Reference Daily Intake (RDI) or Daily

label must include the quantity of eachdietary ingredient per serving. The sourcesof the dietary ingredients may be stated onthe nutrition label or in a separateingredient list. In the case of botanicals,the label must indicate the part of the plantused in the ingredient. Nutrient contentclaims for dietary supplements can be basedon RDIs or DRVs (98), but DSHEAspecifically permits percentage level claimsfor ingredients where a Daily Value (DV) isnot established.

8. New Dietary Ingredients

According to Section 8 of DSHEA, theterm “new dietary ingredient” means “adietary ingredient that was not marketed inthe United States before October 15, 1994,and does not include any dietary ingredientwhich was marketed in the United Statesbefore October 15, 1994.”This section describes the conditions underwhich a new dietary ingredient may be usedin a dietary supplement. Unless aningredient has been “present in the foodsupply as an article used for food in a formin which the food has not been chemicallyaltered,” the manufacturer must provide



FDA with information, based on a history Under Section 11 of DSHEA, the Secretaryof use or other evidence of safety, of the Department of Health and Humansupporting the conclusion that the product Services (HHS) is directed to issue“will reasonably be expected to be safe.” regulations rendering null and void the JuneThis information must be provided at least 1993 Advance Notice of Proposed75 days before introducing a new dietary Rulemaking (ANPR) concerning dietaryingredient into interstate commerce. supplements (49-52).

9. Good Manufacturing Practices 12. Commission on Dietary

In addition to laying the foundation for aregulatory framework for dietary supple- Section 12 of DSHEA mandates thements and their ingredients, DSHEA, under appointment by the President of a commis-Section 9, provides FDA with the authority sion to study and make recommendationsto promulgate good manufacturing practice concerning label claims and statements for(GMP) regulations for supplements. The dietary supplements (pages 5 through 7 ofAct stipulates that any new GMP this Chapter).regulations must be modeled after currentfood GMP regulations and go through therequired rulemaking process, allowing forpublic notice and comment. Section 13 of DSHEA establishes an Office

10. Conforming Amendments

Section 10 of DSHEA makes changes is to explore more fully the potential role ofnecessary for conformance in relevant dietary supplements as a significant part ofsections of FDCA. It amends Section 201 the efforts of the United States to improveof FDCA to provide that a food or dietary health care and to promote scientific studysupplement that bears a statement of of the benefits of dietary supplements innutritional support in accordance with maintaining health and preventing chronicDSHEA is not a drug solely because the disease and other health-related conditions.label or labeling bears such a statement.Section 301 of FDCA is modified to make In fulfilling its duties, as specified inthe introduction of unsafe dietary supple- DSHEA, ODS is to:ments into interstate commerce a violation.Section 403 is amended to state that a ! Conduct and coordinate scientificdietary supplement is not misbranded solely research within NIH relating to dietarybecause the label includes directions, supplements and the extent to whichconditions of use, or warnings. their use can limit or reduce the risk of

11. Withdrawal of the Regulationsand

Notice

Supplement Labels

13. Office of Dietary Supplements

of Dietary Supplements (ODS) within theNational Institutes of Health (NIH).According to the Act, the purpose of ODS

diseases and conditions such as heartdisease, cancer, birth defects, osteo-porosis, cataracts, and prostatism;



! Collect and compile the results ofscientific research relating to dietarysupplements, including data fromforeign sources or NIH’s Office ofAlternative Medicine;

! Serve as the principal advisor to theSecretary and the Assistant Secretaryfor Health and provide advice to theDirectors of NIH and the Centers forDisease Control and Prevention (CDC),and the Commissioner of Food andDrugs on issues relating to dietarysupplements;

! Compile a database on scientificresearch on dietary supplements andindividual nutrients; and

! Coordinate NIH funding relating todietary supplements.

THE COMMISSION ON DIETARYSUPPLEMENT LABELS

1. Charge

Section 12 of DSHEA establishes aCommission on Dietary Supplement Labelsto develop recommendations for theregulation of label claims and statements fordietary supplements. Specifically, DSHEAdirects the Commission to:

. . . conduct a study on, and providerecommendations for, the regulation of label claims and statements for dietarysupplements, including the use ofliterature in connection with the sale ofdietary supplements and proceduresfor the evaluation of such claims.

The Act stipulates that, in making itsrecommendations, the Commission is to:

. . . evaluate how best to providetruthful, scientifically valid, and notmisleading information to consumersso that such consumers may makeinformed and appropriate health carechoices for themselves and theirfamilies.

DSHEA authorizes the Commission to holdpublic hearings around the country tocollect relevant testimony and evidence.

As mandated by DSHEA, the Commis-sion’s seven members are presidentialappointees with expertise and experience inthe manufacture, regulation, distribution,and use of dietary supplements. DSHEAstipulates that three of the members are tobe qualified by scientific training andexperience to evaluate the benefits to healthof the use of dietary supplements and thatone of those three is to have experience inpharmacognosy, medical botany, traditionalherbal medicine, or other related sciences.The composition of the Commission meetsthese requirements.

DSHEA directs the Commission to preparea final report to the President and Congressthat includes the results of its study and anyfindings or recommendations the Com-mission may choose to make, includingrecommendations for additional legislation.

The Act requires that the Secretary ofHHS, within 90 days after the Commissionissues its report, publish in the FederalRegister a notice of any Commissionrecommendations proposing “. . . changesin regulations of the Secretary for theregulation of dietary supplements . . .”,along with a notice of proposed rulemakingon such recommendations. DSHEA also



stipulates that the rulemaking process must in connection with sales. Guidance has alsobe completed within two years after the been developed on associated issues,release of the report. It adds that, in the including the suggested information neededevent that HHS fails to complete the by manufacturers to substantiate statementsrulemaking within two years, the of nutritional support. The safety of dietaryregulations published by FDA on January 4, supplements has been considered by the1994, pertaining to the general Commission because of the relevance ofrequirements covering health claims for safety to the consumer’s ability to makedietary supplements shall become null and “informed and appropriate health carevoid. choices.” In addition, the safety and labeling

2. Charter

DSHEA mandates that the Commission be supplement can be used appropriately. Asestablished as an independent agency within mandated, the Commission also consideredthe executive branch. Because funds the procedures for evaluation of labelauthorized by DSHEA were not statements and claims, and possibleappropriated, the Secretary of HHS allo- approaches to their implementation. Thecated departmental funds to cover the report also explores alternatives foroperating costs of the Commission. manufacturers to make claims for botanicalAccordingly, the Commission was products that might otherwise be made onlychartered by HHS under the Federal indirectly as statements of nutritionalAdvisory Committee Act, rather than support. The Commission considered theformally established as an independent need for consumer research as part of itsagency. Congressional sponsors of DSHEA evaluation of how to provide information towere briefed regarding the reasons for this consumers to enable them to makeorganizational arrangement. informed and appropriate health care

The appointment of the Commission addressed because of their relevance to themembers was announced by the White mandate in Section 12 of DSHEA thatHouse on October 2, 1995. Its charter directs the Commission to study how to(Appendix B) was approved by the provide consumers with information that isSecretary on February 13, 1996. scientifically valid. The Commission

In its discussions at the first and later in this report, as well as the guidance andmeetings, the Commission agreed that the recommendations meet the Commission’scongressional mandate in Section 12 of obligation to report to the President,DSHEA should be interpreted broadly. This Congress, and the Secretary, as specified inapproach is also indicated in its Charter. DSHEA and in the Charter.Thus, the Commission has consideredconceptual issues related to the labeling ofdietary supplements, including NLEAhealth claims and DSHEA statements of Significant events related to activities of thenutritional support, and the use of literature Commission are highlighted in Figure 1.

of a supplement are interrelated, becausethe label indications for use and anywarning information affect how the

choices. Research issues have been

concludes that the scope of matters covered

3. Procedures



The Commission procedures are described tional support on dietary supplementin Appendix C. Individuals and labels; substantiation of the informationorganizations who testified before the and statements on labels; publicationsCommission at the public hearings or who used in conjunction with sales that areotherwise provided formal oral or written exempt from classification as labeling;comments at the request of the Commission and regulation of botanical productsthrough June 24, 1997, are identified in when manufacturers wish to makeAppendices D and E. claims for prevention and treatment of

4. Report

Reflecting the charge to the Commission in and recommendations related to otherDSHEA and in the Commission’s charter, issues identified by the Commissionthis report is addressed to the President, during its deliberations. Topics includeCongress, and the Secretary of HHS. information the public needs to makeAlthough many aspects of the report will be informed health care choices and howof interest to other Federal and State best to make such information availableagencies, the general public, and the dietary to consumers. The Commission con-supplement industry, the primary intent is to sidered mechanisms to improve theprovide guidance to those who are ability of manufacturers of dietaryresponsible for the interpretation and the supplements and Federal and Stateimplementation of DSHEA. The organi- regulators to evaluate the safety ofzation of the report is as follows: products and to support the validity of

! Chapter I summarizes the major labels of these products. Enforcementprovisions of DSHEA and the charge to issues and research needs related tothe Commission. A copy of the legis-lation and Commission charter areAppendices A and B, respectively.

! Chapter II reviews the legislativeand regulatory context surroundingDSHEA. It also summarizes keybackground information related toconsumer use of dietary supplementsand the supplement industry.

! Chapter III discusses the major find-ings, guidance, and recommendationsdeveloped by the Commission. Topicsinclude the safety of dietary supple-ments; general information on dietarysupplement labels; claims on dietarysupplement labels; statements of nutri-

disease.

! Chapter IV presents findings, guidance,

claims and statements made on the

Commission on DietarySupplement Labels

Figure 1.

94 951994 1995

OCTOBER 25

President Clintonsigned Dietary

Supplement Healthand Education

Act of 1994into law

OCTOBER 6-7

House and Senate passed Dietary

Supplement Healthand Education

Act of 1994

NOVEMBER

White House Personnel Office

initiated solicitationof nominees to

the Commission onDietary Supplement

Labels from publicand private sectors

OCTOBER 2

President Clintonannounced intentionto appoint theseven-memberCommission

NOVEMBER 9

PresidentClinton

appointedthe sevenmembers

of theCommission

JULY 14

Executive Director ofCommission appointed

NOVEMBER 13

Commission Chairand ExecutiveDirector developedschedule forCommission



Chronology: October 1994 toNovember 1997

96 971996 1997

FEBRUARY 2

CommissionChair andExecutive

Directordeveloped

schedule ofmeetings,

procedure foractivities.Executive

Directorarrangedmeetingsbetween

CommissionChair andmembers.Meetings

held

FEBRUARY 16

Commissionheld first

information-gathering

meeting inWashington, DC

MARCH 8

Second meeting:Salt LakeCity, Utah

APRIL 26

Third meeting:San Francisco,

California

JUNE 6

Fourthmeeting:Orlando,Florida

JULY 9

InterestedCongressionalstaff briefedat theirrequest onprogress ofthe CommissionthroughJune 30, 1996

SEPTEMBER 19-20

Fifthmeeting:Reston,Virginia

OCTOBER 24-25

Sixthmeeting:Washington,DC

DECEMBER 16

Seventhmeeting:Washington, DC

MARCH 4

Eighthmeeting:

Baltimore,Maryland

JUNE 20

InterestedCongressionalStaff briefed onreasons forrelease of andcontentsof Commission�sdraft report

JUNE 24

Draft reportof theCommissionreleased forpubliccomment

AUGUST 14-15

Ninth meeting heldto review comments

and suggestionsreceived from public

on draft report,Washington, DC

NOVEMBER

Final Report of theCommission delivered tothe President, Congress,

and the Secretaryof the Department

of Health and HumanServices. Final reportreleased to the public





consumer use of dietary supplements arealso discussed.

The findings, guidance, and recommenda-tions of the Commission are presented ineach section of Chapters III and IV.

! FINDINGS are the conclusions reachedby the Commission during its delibera- The Commission on Dietary Supplementtions and are based on the information Labels was aware of the public interest inand data received and reviewed by the its work and desired to receive publicCommission. comment on its draft report. Therefore, a

! GUIDANCE represents advice to specificagencies, groups, or individuals.Guidance should be considered by theidentified recipients as they develop orimplement activities related to theavailability of dietary supplements in themarketplace.

! RECOMMENDATIONS are indicated assuch and identify the intendedrecipients. Recommendations that callfor consideration of changes in existingregulations, development of newregulations, or legislative action are soindicated.

draft report was released for publiccomment on June 24, 1997. Whilecomments were requested by August 4,1997, the Commission accepted submis-sions through September 15, 1997.Approximately 400 comments on the draftreport were received from the public andevaluated before completion of this finalreport.

ENDNOTE

1. Statement of Agreement: “This statement comprises the entire legislative history for the Dietary SupplementHealth and Education Act of 1994, S.784. It is the intent of the chief sponsors of the bill (Senators Hatch, Harkinand Kennedy, and Congressmen Richardson, Bliley, Moorhead, Gallegly, Dingell, Waxman) that no other reportsor statements be considered as legislative history for the bill.

1. The bill does not affect the Food and Drug Administration’s existing authority under the Federal Food,Drug and Cosmetic Actto prohibit the import or sale of any product marketed as a drug in a foreigncountry.

2. In section 201(ff)(3)(B)(ii), added by section 3 of the bill, the term ‘substantial clinical investigations’does not include compassionate investigational new drug applications or an investigational new drugapplication submitted by a physician for a single patient.

3. Section 403B, added by section 5, does not apply to a summary of a publication other than an officialabstract of a peer-reviewed scientific publication.

4. Section 403(r)(6)(A), added by section 6, does not permit premarket approval or require premarketreview by the FDA of any statement permitted under that provision.

5. In section 413(a)(1), added by section 8, the term ‘chemically altered’ does not include the followingphysical modifications: minor loss of volatile components, dehydration, lyophilization, milling, tinctureor solution in water, slurry, powder, or solid in suspension.”


Chapter II

BACKGROUND ON DIETARY SUPPLEMENTS

PERTINENT LEGISLATION ANDREGULATIONS

The Federal Food, Drug, and Cosmetic Act dietary use containing added vitamins and/orof 1938, as amended by DSHEA, is the minerals (66). The minimum dailyprincipal law governing dietary supplements. requirement (MDR) was established as theUnder FDCA, FDA has jurisdiction over reference standard for expressing the dailyproduct safety and labeling issues. This need for a vitamin or mineral. The 1941chapter provides background on FDA’s regulations placed no restriction on theregulation of dietary supplements. amount or variety of nutrients that could be

Dietary supplements are also subject to otherFederal laws. The most relevant of these, the From 1962 to 1976, FDA attempted toFederal Trade Commission Act (5 U.S.C. revise these regulations to replace the MDR45), provides the Federal Trade Commission with a new reference standard—the U.S.(FTC) with the authority to regulate Recommended Daily Allowance (U.S.advertisements for all consumer products, RDA)—and to establish a standard ofincluding supplements. Relevant FTC identity restricting the amounts and com-policies are discussed in Chapter III. binations of vitamins and minerals that could be marketed as dietary supplements. FDACurrently, Congress is considering changes also proposed to require a label disclaimerin some provisions related to dietary on vitamin or mineral supplements statingsupplements, such as health claims under that:NLEA; however, this report deals withFDCA as amended by DSHEA, as it existedon September 2, 1997.

1. 1906 Through 1994

The legislative and regulatory historyconcerning dietary supplements since 1906is extensive. A brief synopsis of events thatled up to the passage of NLEA in 1990 andDSHEA in 1994 may be instructive.

The Pure Food and Drug Act of 1906 dealtwith unsafe foods, unregulated elixirs, andmisbranded products. The 1938 FDCAestablished a category of foods for specialdietary use and required the labels of suchfoods to provide information on theirvitamin, mineral, or other dietary properties.

In 1941, FDA established regulationsgoverning the labeling of vitamin and mineralsupplements and other foods for special

included in a supplement or a fortified food.

Vitamins and minerals are supplied inabundant amounts by commonlyavailable foods. Except for personswith special medical needs, there is noscientific basis for recommendingroutine use of dietary supplements (65).

Two years of hearings, from 1968 to 1970,led FDA to abandon the proposeddisclaimer, but the bulk of the proposalremained intact. Quantities of vitamins andminerals were to be limited generally to 150percent of the U.S. RDA, and only a fewcombinations of vitamins and minerals wereto be allowed. Products with higher levels ofnutrients or different combinations ofnutrients would be subject to review by an

Chapter II Background on Dietary Supplements


expert advisory committee as part of FDA’s final rules were published on September 23,over-the-counter (OTC) drug review. 1997, as this report was being completed

These special dietary use regulations and thedietary supplement standards of identity In 1990, Congress passed landmarkwere finalized in 1973, overturned and legislation (NLEA) that affected nutritionremanded to the agency by the courts in labeling of food and dietary supplements.1974, revised and reproposed in 1975, NLEA mandated that virtually all food labelslargely invalidated by legislation early in not only must contain specific information1976, revised and reissued late in 1976, on nutrient content but also could makeagain overturned by the courts in 1978, and claims relating specific nutrients to diseasesultimately withdrawn by FDA in 1979 or disorders. Such “health claims” were to(62,64,93,94). When FDA withdrew those be based on significant scientific agreementregulations, it withdrew them in their on the validity of the claimed relationshipentirety—the basic labeling provisions that between the nutrient and the disease. Inhad been upheld as well as the provisions developing the process for approval ofthat had been overturned by the courts. health claims, FDA established standards for

In 1976, Congress passed vitamin and meet the criteria for approval of healthmineral legislation (the Rogers/Proxmire claims. amendment) that prohibited FDA fromclassifying vitamin and mineral supplements NLEA directed FDA to consider a differentas drugs based solely on their combinations approval procedure and scientific evaluationor potency (unless drug claims were made), standard for health claims made aboutfrom establishing a standard of identity for dietary supplements than those used forthese products, and from limiting the foods. NLEA also directed FDA toquantity or combination of nutrients in them, consider a list of 10 potential health claimsexcept for reasons of safety. The 1976 for specific nutrient/disease relationships.legislation also incorporated FDA’s 1941definition of special dietary use into FDCA. In the process of establishing mandatory

Since the 1973 regulations were stayed proposed to replace the U.S. RDAs withpending judicial review and ultimately new RDIs based on “mean requirements”withdrawn, no formal labeling regulations for vitamins and minerals, which would havefor dietary supplements were in effect from had the effect of lowering the daily reference1973 to 1994, but most manufacturers amounts for many nutrients. FDA alsoadopted the format set forth in the 1973 proposed some basic requirements for healthregulations. FDA finalized nutrition labeling claims that appeared to disallow healthregulations for dietary supplements in claims for many dietary supplements. January 1994 (45,46,47), but these labelingprovisions were amended by DSHEA in In 1992, Congress passed the DietaryOctober 1994. Revised nutrition labeling Supplement Act which essentially prohibitedregulations for dietary supplements were the implementation of NLEA with respectproposed in December 1995 (40-43). The to dietary supplements except for the

(26-31).

the types and levels of evidence necessary to

nutrition labeling requirements (55), FDA



approved health claims. This legislation, in Representatives. The bill would haveeffect, established a moratorium on the repealed certain provisions of NLEA andlabeling of dietary supplements to permit DSHEA and would have established a singleCongress and FDA time to consider various claims category that would encompassrelated issues. It also required that regula- statements that currently fall under thetions pursuant to NLEA regarding dietary classification of health claims, as well assupplements be reproposed. statements of nutritional support. No action

On June 18, 1993, FDA published a Congress. In 1997, the Food and Drugcomprehensive ANPR concerning the Administration Modernization andregulation of dietary supplements (52). This Accountability Act (S 830) was introducedANPR referenced a number of factors, into the Senate and the Food and Nutritionincluding increased consumer use of dietary Information Reform Act (HR 2469) wassupplements, an internal FDA three-year introduced into the House of Representa-review of possible regulatory approaches, tives. Both 1997 bills include changes tooccurrence of eosinophilia myalgia syndrome procedures for the authorization of healthas a consequence of L-tryptophan use, and claims by allowing other Federal agencies toreports of serious illness as a result of using determine whether significant scientificcertain botanical supplements. agreement exists. Action on both bills is

The 1993 ANPR suggested, among other tory actions resulting from the passage ofprovisions, that vitamins and minerals be DSHEA (Table 1).limited to low multiples of the RDIs, thatsome botanical products were inherentlydrugs and not dietary supplements, and thatmany dietary supplements, including amino President Clinton attributed the moveacids, were unapproved food additives. The toward legislative and regulatory reform forANPR elicited considerable protest from the dietary supplements to a growing interest onpublic and the dietary supplement industry the part of the American public in the use ofbecause FDA appeared to be reproposing dietary supplements. In signing DSHEAregulatory provisions withdrawn or struck into law, he stated: down by court actions in previous years.The ANPR was a significant motivatingfactor in industry and congressional effortsto develop and secure passage of DSHEA in1994.

2. 1994 to the Present

Since the passage of DSHEA, both Congressand FDA have put forth related legislativeand regulatory initiatives. In 1995, the Foodand Dietary Supplement Consumer Act (HR1951) was introduced in the U.S. House of

on HR 1951 was taken by either House of

pending. FDA has advanced various regula-

CONSUMER USE

. . . in an era of greater consciousnessamong people about the impact of whatthey eat on how they live, indeed, howlong they live, it is



Table 1

REGULATIONS RELATED TO DIETARY SUPPLEMENTS

SINCE PASSAGE OF DSHEA

DATE ACTION CITATION

April 1995 Pursuant to DSHEA’s exclusion of dietary ingredients of dietary Federal Register, Vol. 60,supplements from food additive regulation, FDA withdrew itsrelevant “regulatory guidance.”

April 19, 1995, p. 19597

December FDA issued a proposed rule to increase flexibility of label claim Federal Register, Vol. 60,1995 language and refine other NLEA provisions in response to

citizen petitions.December 21, 1995, pp.66206-66227.

December FDA issued a proposed rule concerning food label Federal Register, Vol. 60,1995 requirements for nutrient content claims, health claims and

statements of nutritional support for dietary supplements.December 28, 1995, pp.67176-67184

December FDA issued a proposed rule concerning the definition for “high Federal Register, Vol. 60,1995 potency” claims for dietary supplements and the definition of

“antioxidant” when used in nutrient content claims of dietarysupplements.

December 28, 1995, pp.67184-67194

December FDA issued proposed rules governing the labeling of dietary Federal Register, Vol. 60,1995 supplements with respect to the statement of identity, nutrition

labeling and ingredient labeling.December 28, 1995, pp.67194-67224

March FDA issued a final rule on health claims and label statements Federal Register, Vol. 61,1996 concerning folate and neural tube defects. March 5, 1996, pp. 8752-

8781

April 1996 FDA declared that DSHEA does not apply to dietary Federal Register, Vol. 61,supplements intended for use in animals other than humans. April 22, 1996, pp. 17706-

17708

August FDA issued a final rule providing for a health claim for sugar Federal Register, Vol. 61,1996 alcohols and nonpromotion of dental caries. The health claim

may be used with eligible foods and dietary supplements.August 23, 1996, pp.43433-43447

September FDA issued a proposed rule spelling out the procedure by Federal Register, Vol. 61,1996 which companies would notify FDA of dietary supple-ment

products bearing statements of nutritional support.September 27, 1996, pp.50771-50774

September In response to DSHEA’s new dietary ingredient provisions, FDA Federal Register, Vol. 61,1996 published a proposed rule that would establish the procedure

for premarket notification of a new dietary ingredient.September 27, 1996, pp.50774-50778

January FDA issued a final rule on required warning statements and Federal Register, Vol. 62,1997 packaging requirements for iron-containing dietary supplements

and drugs.January 15, 1997, pp.2218-2250

January FDA issued a final rule providing for a health claim for soluble Federal Register, Vol. 62,1997 fiber from whole oats and reduced risk of coronary heart

March dietary supplements. FDA amended the final rule in March 19971997 to clarify the regulation.

disease. The health claim may be used with eligible foods andJanuary 23, 1997, pp.3584-3601Federal Register, Vol. 62,March 31, 1997, pp.15343-15344

Table 1 (Continued)


DATE ACTION CITATION


February Acting on DSHEA’s provision that HHS may prescribe good Federal Register, Vol. 62,1997 manufacturing practices for dietary supplements, FDA issued

an advance notice of proposed rulemaking in February 1997announcing that it was considering whether to institute rulemak-ing to develop current good manufacturing practice regulationsfor dietary supplements and dietary supplement ingredients.

February 6, 1997, pp.5700-5709

May 1997 FDA proposed to extend the health claim on the association of Federal Register, Vol. 62,soluble fiber and reduced risk of coronary heart disease toinclude soluble fiber from psyllium husks.

May 22, 1997, pp. 28234-28245

June 1997 FDA proposed rules on dietary supplements containing Federal Register, Vol. 62,ephedrine alkaloids. June 4, 1997, pp. 30678-

30724

July 1997 FDA published a final rule in which the agency did not modify Federal Register, Vol. 62,the definition of “imminent hazard to the public health” in 21CFR 2.5.

July 23, 1997, pp. 39439-39440

September FDA issued a final rule amending food labeling regulations con- Federal Register, Vol. 62,1997 cerning statements of identity and nutrition labeling of dietary

supplements. The rule also revokes Compliance Policy Guide530.400 (CPG 7121.02). Effective date: March 23, 1999.

September 23, 1997, pp.49826-49858

September FDA published a final rule amending food labeling requirements Federal Register, Vol. 62,1997 for nutrient content claims, health claims, and statements of

nutritional support for dietary supplements. Effective date:March 23, 1999.

September 23, 1997, pp.49859-49868

September FDA published a final rule amending the definition of “high Federal Register, Vol. 62,1997 potency” claims for dietary supplements and amending the

definition of “antioxidant” for use in nutrient content claims fordietary supplements. Effective date: March 23, 1999.

September 23, 1997,pp.49868-49881

September FDA responded to comments on a final rule establishing a Federal Register, Vol. 62,1997 uniform date of January 1, 2000, for compliance with food

regulations issued between January 1, 1997, and December31, 1998. Effective date: December 27, 1996.

September 23, 1997, pp.49881-49883

September FDA issued a final rule on notification procedures for statements Federal Register, Vol. 62,1997 on dietary supplements. Effective date: October 23, 1997. September 23, 1997, pp.

49883-49886.

September FDA issued a final rule on premarket notification for new dietary Federal Register, Vol. 62,1997 ingredients. Effective date: October 23, 1997. September 23, 1997, pp.

49886-49892.



appropriate that we have finallyreformed the way the Governmenttreats consumers and these supplementsin a way that encourages good health(12).

In enacting DSHEA, Congress estimatedthat “almost 50 percent of the 260,000,000Americans regularly consume dietarysupplements of vitamins, minerals, orbotanicals as a means of improving theirnutrition” (Appendix A). In that same year,the United States was expected to spendmore than $1 trillion on health care—about12 percent of the country’s gross nationalproduct. Congressional findings reported inDSHEA state that “preventive healthmeasures, including education, goodnutrition, and appropriate use of safenutritional supplements will limit theincidence of chronic diseases, and reducelong-term health care expenditures.” TheAct adds that “consumers should beempowered to make choices aboutpreventive health care programs based ondata from scientific studies of health benefitsrelated to particular dietary supplements.”

A variety of sources confirm the con-gressional finding that a significant portionof the U.S. population uses dietary supple-ments. Data from a large probability sampleof the U.S. population from the thirdNational Health and Nutrition ExaminationSurvey for 1988-94 indicated that asubstantial percentage of the U.S. populationused dietary supplements (defined asincluding vitamins, minerals, amino acids,botanicals, and other products) (142). Datafrom this survey suggest that for the totalU.S. population, the prevalence of dietarysupplement use by children 3-5 years of ageis about 48 percent, while the prevalence ofuse by adults 20 years of age to over 80

years of age ranges from about 36 percent to51 percent. Dietary supplement usageappears to differ by age, with increasing useby older adults (35.8 percent for ages 20-29years, 46.2 percent for ages 50-59 years, and50.6 percent for ages 80 years and older). Inthe total sample surveyed, the prevalence ofsupplement use by women of all ages andethnicities was higher than that by men (42.9percent versus 34.5 percent on an age-adjusted basis, respectively).

Similarly, use of dietary supplements by allage groups appears to be greater in non-Hispanic whites (41.6 percent) than in non-Hispanic blacks (30.2 percent) or Mexican-Americans (30.5 percent). In addition, forall groups, the higher the income, the greaterthe use of dietary supplements. Further, theprevalence of dietary supplement useincreases with years of education in allgroups.

According to National Health InterviewSurveys from 1987 to 1992, regular dailyuse of certain specified supplements(multivitamins, vitamin A, vitamin C, vitaminE, or calcium) remained at about 24 percent.In both 1987 and 1992, 9 percent of thepopulation reported daily intake of morethan one type of the specified supplements,5 percent took two types of supplements,and 0.3 percent took all five of the types ofsupplements included in the survey. Acomparison of the 1987 and 1992 NationalHealth Interview Survey results indicates a4.9 percent decline in the total populationreporting use of any vitamin or mineralsupplement (51.1 percent versus 46.2percent) (130).

According to data collected by Multi-Sponsor Surveys, Inc., presented during a



Commission hearing by Hoffman-La Roche According to a telephone survey of 1,000Inc., between 30 and 40 percent of the U.S. individuals conducted by Applied Bio-population use vitamin and mineral supple- metrics, some of the reasons reported byments (72). In 1995, 38 percent of adults consumers as to why they take supplementsused vitamin and mineral supplements. This are to prevent disease or boost immunity, torepresents approximately 73 million adults, increase energy, to improve fitness, toan increase of some 13 million users since increase alertness or mental activity, to1991. These data suggest that about 33 reduce stress, and to treat a medical problempercent of adults, or 63 million people, take (131). supplements every day or nearly every day.Of these, approximately 49 percent consume The sources cited above vary in theirone vitamin and mineral supplement per day estimates but are consistent in revealing thatthat supplies the U.S. RDA. Another 27 a substantial percentage of the U.S.percent take two or three supplements per population takes dietary supplements ofday, usually a multivitamin plus calcium, some kind.vitamin C, or vitamin E. One adult user inten takes six or more supplement products ofany kind per day (72).

While the usage of vitamin and mineral According to congressional estimates at thesupplements is well documented, collection time DSHEA was enacted in 1994, someof data on the use of other categories of 600 dietary supplement manufacturers in thesupplements (e.g., botanicals and amino United States were producing approximatelyacids) began only recently. A survey of 4,000 products, with total annual sales of1,945 individuals conducted by FDA in 1994 such products reaching at least $4 billionindicated that 51 percent of adults 18 years (Appendix A).of age and older used some type ofsupplement (127). Of those supplement The supplement industry in the United Statesusers, 73 percent were considered to be is represented, for the most part, by five“light users” (used one or two supplements) trade organizations. The American Herbaland 27 percent “heavy users” (used three or Products Association represents some 200more supplements), 10 percent were amino companies and individuals who grow,acid users, and 16 percent were botanical import, process, market, and/or manufactureproduct users. In 1995, FDA conducted a botanical products (3,87). The Council forsimilar survey and found an increase in the Responsible Nutrition represents over 80use of some supplements. Of 1,001 adults companies in the dietary supplement industryqueried, the survey indicated that 55 percent (14). The National Nutritional Foodsused some type of supplement. Of those, 72 Association has some 4,000 memberspercent were light users, 28 percent were representing manufacturers, wholesalers,heavy users, 16 percent used amino acids, distributors, and retailers of natural productsand 22 percent used botanical products (75). The Utah Natural Products Alliance(127). represents the interests of dietary supplement

CHARACTERISTICS OF THE U.S.DIETARY SUPPLEMENT INDUSTRY

companies in Utah, which generate sales inexcess of $1 billion per year (77). The



Nonprescription Drug Manufacturers of combination products. Within the vitaminAssociation is composed of manufacturers and mineral category, the top six productand distributors of nonprescription drugs and types are multivitamins (with or withoutcombination or single-ingredient vitamin and minerals), vitamin E, vitamin C, iron,mineral products (143). calcium, and B vitamins (15). Multivitamin

A number of factors, including rapid growth all retail sales in the vitamin and mineralof the dietary supplement industry, an category. These data are consistent withincrease in consumer interest in such information on extent of use by adultsproducts, particularly botanical products, presented in testimony to the Commissionand the variety of avenues through which (72).consumers may obtain supplements, havehampered efforts to collect accurate data on Some 1,500 to 1,800 botanicals are sold inthe sale and use of such products. the United States as dietary supplements or

A review of the global dietary supplement to a survey of the U.S. botanical supple-industry (vitamins and minerals, herbs and ments market, the top 10 botanical productsbotanicals, sports nutrition) conducted by sold at selected U.S. health food stores inthe Nutrition Business Journal and its 1995 were echinacea, garlic, goldenseal,affiliate EuroConsult, Inc., indicated that the ginseng, ginkgo, saw palmetto, aloe, maworldwide dietary supplement industry huang, Siberian ginseng, and cranberry (9).registered $28.2 billion in consumer sales in1995 (6). Of that total, Europe accounted The dietary supplement industry alsofor $9.5 billion, the United States $8.2 represents a major segment of the U.S.billion, Japan $5.2 billion, other Asian import and export trade market. Accordingcountries $3.2 billion, and Canada $0.7 to 1994 trade data from the Bureau ofbillion. In the United States, sales of Census, U.S. Department of Commerce,vitamins and minerals alone were $4.8 billion “medicinal herbs” imported into the Unitedin 1995, followed by botanical products at States included licorice roots, oriental$2.5 billion and sports nutrition supplements ginseng roots (cultivated and wild), mintat $0.8 billion. However, in Europe, leaves, plants and plant parts used as herbalconsumer sales were highest for botanicals teas, ephedra powder, and substances used($6 billion), followed by vitamins and principally to promote healing. “Medicinalminerals ($3.1 billion) and sports nutrition herbs” exported from the United Statesproducts ($0.4 billion) (6). include American ginseng, echinacea,

Vitamin and mineral products include single- palmetto (9).nutrient supplements as well as a multiplicity

preparations constitute about 31 percent of

ethnic traditional medicines (77). According

ginkgo, goldenseal, peppermint, and saw


Chapter III

MAJOR ISSUES AND RECOMMENDATIONS RELATED TO

LABELING OF DIETARY SUPPLEMENTS

The Commission’s charge to address major are unsafe or adulterated, it should notissues relative to the labeling of dietary take any actions to impose unreasonablesupplements was reiterated in public regulatory barriers limiting or slowingtestimony presented at meetings held the flow of safe products and accuratethroughout the country and in written information to consumers.submissions to the Commission. DSHEAmandated that the Commission review and FDCA defines the conditions under which amake recommendations on label claims, food may be considered “adulterated” (i.e.,substantiation of claims, and literature unsafe) (Section 402(a)). DSHEA subjectsavailable to the public. In addition, the dietary supplements to the original adultera-Commission identified issues related to label tion provisions governing food and addsclaims for botanical supplements. This additional conditions (Section 402(f)).chapter outlines the Commission’s delibera- Specifically, DSHEA indicates that a dietarytions and findings on these issues and supplement is adulterated:provides guidance and recommendations.

SAFETY OF DIETARYSUPPLEMENTS

Because of the concerns relative to safetyissues expressed in the public submissions,the Commission included safety as a majortopic in its deliberations.

1. DSHEA Provisions on Safety

In reflecting on issues associated with safety,during the creation and passage of DSHEAin 1994, Congress reached the followingconclusions:

! Almost 50 percent of the U.S. popula-tion consume dietary supplements;

! Dietary supplements are safe within abroad range of intake, and safety prob-lems of supplements are relatively rare;and

! Although the Federal government shouldtake swift action against products that

If it is a dietary supplement or containsa dietary ingredient that—A) presents a significant or

unreasonable risk of illness orinjury under—(i) conditions of use recommended

or suggested in labeling, or(ii) if no conditions of use are

suggested or recommended inthe labeling, under ordinaryconditions of use;

B) is a new dietary ingredient forwhich there is inadequateinformation to provide reasonableassurance that such ingredient doesnot present a significant orunreasonable risk of illness orinjury;

C) the Secretary declares to pose an imminent hazard to public health orsafety, except that the authority tomake such declaration shall not bedelegated and the Secretary shallpromptly after such a declarationinitiate a proceeding in accordancewith Sections 554 and 556 of Title5, United States Code, to affirm orwithdraw the declaration; or

Chapter III Major Issues and Recommendations Related toLabeling of Dietary Supplements


D) is or contains a dietary ingredient for food in a form in which thethat renders it adulterated under food has not been chemicallyparagraph (a)(1) under the altered.conditions of use recommended or (2) There is a history of use orsuggested in the labeling of such other evidence of safetydietary supplement. establishing that the dietary

Under the authority created by DSHEA,FDA can bring enforcement action againstan existing supplement if it presents anunreasonable or significant risk of harm.While not yet judicially interpreted, in manyrespects the test for safety under the newprovisions of DSHEA is similar to the testenunciated by the Supreme Court in a land-mark 1914 case concerning addition ofpoisonous and deleterious substances in food supplement provides the(138). Under this case, safety is to berelated to the quantity of a substance and therisk when the facts are reasonably con-sidered.

Under DSHEA, the safety of dietary supple-ments is determined based on the conditionsof use recommended or suggested in thelabeling (Appendix A). DSHEA exemptsdietary supplement ingredients from the foodadditive provisions of FDCA and establishesconditions for the marketing of new dietaryingredients not marketed in the UnitedStates as dietary supplements prior toOctober 15, 1994. The new provisions haveyet to be tested in court.

DSHEA stipulates that a dietary supplementthat contains a new dietary ingredient:

. . . shall be deemed adulterated underSection 402(f) unless it meets one ofthe following requirements:(1) The dietary supplement con-

tains only dietary ingredientswhich have been present in thefood supply as an article used

ingredient when used under theconditions recommended orsuggested in the labeling of thedietary supplement willreasonably be expected to besafe and, at least 75 daysbefore being introduced ordelivered for introduction intointerstate commerce, the manu-facturer or distributor of thedietary ingredient or dietary

Secretary with information,including any citation topublished articles, which is thebasis on which themanufacturer or distributor hasconcluded that a dietarysupplement containing suchdietary ingredient will reason-ably be expected to be safe.

FDA approval is not required with regard toadequacy of substantiation. If FDA objectsto marketing of the ingredient, the agencymust initiate enforcement action. New usesof an existing supplement, or an increase inthe recommended dose, does not make asupplement “new” for purposes of the sub-stantiation requirement.

Under DSHEA, FDA must show affirma-tively, in court, that an unreasonable risk isposed by consumption of a dietary supple-ment. The agency need not show that injuryhas occurred, only that a reasonable possi-bility of harm exists. Under provisions inDSHEA, before reporting a violation to theU.S. attorney for civil enforcement action,



FDA must provide 10 days’ notice to the such reports are found, they often are single-affected party as well as an opportunity for case reports involving an allergenic reactionthe affected party to present views relative or toxicity due to improper labeling, orto the alleged violation, unless an imminent adulteration, or an idiosyncratic reactionhazard to public health or safety exists. even though the product was taken under

2. Good Manufacturing Practices

Dietary supplements are considered foods However, there are exceptions in which theand are subject to requirements of “Current use of botanical products has raised concernsGood Manufacturing Practice in Manufact- about safety. Botanical products such asuring, Packing, or Holding Human Food” comfrey root (Symphytum officinale L.),(108). These regulations provide guidelines which contains hepatotoxic pyrrolizidinewith regard to maintenance of buildings and alkaloids (86), pose a potential health haz-facilities, requirements for food handlers, ard. There also has been consumer concernand cleanliness of equipment, as well as and State regulatory response over frequentprocedural requirements for maintaining or protracted use of foods or dietary supple-safety during the production and processing ments that contain senna (Cassia senna L.)of foods. (73). In countries other than the United

DSHEA specifically authorizes FDA to carcinogens or tumor promoters are usedestablish dietary supplement GMPs. Recog- medicinally (22,90), even though other well-nizing this perceived need, major industry known toxic plants usually are not consumedgroups in 1995 jointly prepared extensive (18-20).revisions to the food GMPs that addressaspects of manufacturing practices used bythe dietary supplement industry. These pro-posed GMPs for dietary supplements were Section 301 of FDCA provides for broadsubmitted to FDA and subsequently pub- enforcement powers in regard to adulter-lished as an ANPR in the Federal Register ation and misbranding of foods, including(32). The Commission supports these efforts dietary supplements. The Commission rec-of FDA and the industry to develop appro- ognizes the importance of having adequatepriate GMPs for dietary supplements. and timely enforcement procedures for

3. Safety of Botanicals

The Commission recognizes that most that preserves the availability of safebotanical products taken as dietary supple- products. The apparent safety of the majorityments in the United States are safe when of products now marketed as dietaryused as directed on labels. There are rela- supplements actually increases the import-tively few reports in the scientific literature ance of having adequate enforcementthat indicate potential or actual toxicity mechanisms, because consumers may thenfollowing the use of these products. When assume that a wide margin of safety auto-

proper conditions of use and within reason-able dose limitations (23).

States, some plants containing known

4. Federal Enforcement Issues

products marketed as dietary supplementsthat are not safe or have a high potential forabuse while maintaining a regulatory climate



matically applies to any product classified as qualitative and quantitative analysis ofa dietary supplement. products. Thus, should FDA have reason to

Recent events associated with products might have to develop and validate ancontaining ephedrine alkaloids illustrate appropriate analytical methodology tothese safety and enforcement concerns. determine composition, presence of toxicDuring Commission hearings, some pre- substances, or adulteration. Similarly, FDAsenters expressed concern about the safety might need to establish the identity of plantof products containing ephedrine alkaloids. parts in certain products. Such efforts areEvidence that such products were implicated resource intensive and may be costin numerous adverse reactions, including prohibitive for an agency with a broad rangefatalities, throughout the country was pre- of regulatory responsibilities. These resourcesented. However, FDA has only recently issues arise not only with regard to safety,proposed rules to define the conditions but also with respect to the appropriatenessunder which products containing ephedrine of label claims. alkaloids would be considered a “significantor unreasonable” risk to health and safety The Commission observed that under(33). The Commission is aware of the prob- Section 402(f)(2) of FDCA added bylems of analytical methodology, identifi- DSHEA, FDA must notify a manufacturer,cation of the products implicated, and the distributor, or other person against whomstrength of evidence related to possible civil action is pending at least 10 days incausation of several deaths associated with advance of the filing of the civil action on theuse of products containing ephedrine alka- supposed violation. This provision allowsloids. Despite the difficulty of making clear the company or individual an opportunity toconclusions based on the reported effects of respond to the alleged violation, both orallythese products, the Commission questions and in writing. The product may continue towhether the industry and FDA have re- be marketed during the 10-day period unlesssponded as promptly to these incidents as the Secretary declares it an “imminentwould be in the best interest of the public. hazard.” DSHEA does not modify theSome Commission members hold that the definition of “imminent hazard” (96) butdelay in action by FDA has served to states that the authority to declare anundermine public confidence in the agency’s imminent hazard cannot be delegated. Thus,commitment to enforce DSHEA. The full in the case of action against a potentiallyCommission urges FDA to take a proactive hazardous dietary supplement ingredient,stance in communicating its position to the regulatory approval at several additionalpublic in such cases and in pursuing legal levels must be sought and obtained. That is,action where justified. FDA staff must have sufficient information

FDA’s resources may limit its ability to take General Counsel and Commissioner, but alsoeffective enforcement action, especially the HHS General Counsel and Secretary.when extensive scientific analysis is required. These additional requirements areFor example, for many ingredients, there are appropriate but increase the time needed, theno well-accepted analytical techniques for resources required, and the effort expended.

initiate action against a product, the agency

and data to convince not only the FDA



Thus, to invoke this statutory provision may an acceptable directive that its member statesrequire decisions about administrative and could use to enact conforming lawsregulatory priorities as well as public health reflecting their choice of the form andand safety. method of implementation (95). The Euro-

5. State Enforcement Issues

Representatives of several States who the presence of contaminants and naturalprovided testimony to the Commission noted toxins. Some countries have approached thethe absence of uniformity in regulations safety of dietary supplements by planning orregarding dietary supplements among the developing lists of ingredients that areStates. They also commented on the permitted or not permitted (95).demands on enforcement resources andindicated that, at the local level, staff exper- In addition, many countries have a mechan-tise and time as well as fiscal resources for ism to document adverse health effects. Forenforcement are limited. These representa- example, in Australia, the Adverse Drugtives emphasized the need to provide FDA Reactions Advisory Committee collects datawith sufficient resources to fulfill its and issues warnings, as necessary, about theresponsibilities and noted that a cutback in side effects of various supplements (81,95).the budget and efforts at the Federal level In the United Kingdom, the National Poisonswould increase the regulatory burden of the Unit reviewed, retrospectively andStates. They also expressed concern about prospectively, cases of suspected poisoningthe wide and uncontrolled range of from exposure to traditional remedies andinformation available on the Internet. In food supplements from 1983 until 1991discussing specific instances in which States (120). In France, the Licensing Authorityhad taken enforcement action, representa- and Pharmacopoeial Authority maintains atives of State health departments and public pharmacovigilance system to gain an over-health organizations directed the Commis- view of the use and adverse effects ofsion’s attention to the plethora of locally botanicals (70). In addition, the Worldprepared and marketed products that might Health Organization (WHO) maintains anot enter interstate commerce with which Collaborating Center for International Drugthey had to contend as well as products in Monitoring in Uppsala, Sweden, which mayethnic markets that were either not labeled in be expanded to cover botanical remediesEnglish or not labeled at all. (21).

6. Postmarketing Surveillance

The safety of foods including dietary reactions to consumer products. The Associ-supplements is a concern of all responsible ation of Poison Control Centers maintainsgoverning bodies worldwide. For example, records on all adverse events reported to athe European Commission continues to national network of Poison Control Centers.work on integrating multinational concerns The USP urges health care practitioners toabout the safety of dietary supplements into report adverse effects through its Practi-

pean Commission has raised several issuesregarding safety, including the potentialexcessive intake of dietary supplements and

In the United States, there are a number ofvoluntary systems for reporting adverse



tioners’ Reporting Network. FDA maintains complaint. A report may be fragmentary andsystems for postmarket reporting of adverse of uneven quality. In addition, there may bereactions to drugs, biologics, devices, and a long lag time between the event and thespecial nutritional products, including dietary receipt of the complaint. Difficulties insupplements. For example, FDA requires obtaining comprehensive information on thereports of serious adverse reactions for new product used and on the health of the con-drugs (114). The Adverse Reaction sumer are also often encountered. DespiteMonitoring System is a passive surveillance these limitations, however, the systems servereporting system for complaints of adverse to alert public health officials about potentialreactions or events associated with foods problems.and dietary supplements (48). MedWatch isan analogous passive surveillance system fornotification of adverse events related tomedications and devices (78,79). These andother FDA passive surveillance systems,such as the Drug Quality Reporting Systemand the Office of Regulatory Affairs Con-sumer Complaint System, are voluntary—there is no legal requirement for individuals,organizations, or facilities to report adversereactions to these FDA systems. Thesesystems provide a monitoring tool foridentifying potentially serious public healthissues that may be associated with the use ofa particular product or type of product. Thestrengths of these systems include their largescale surveillance and their cost effective-ness.

However, as with all passive surveillancesystems, these systems have certainweaknesses. Reports that are received needcritical review to appropriately determine thelikely cause. Otherwise, erroneousconclusions might be reached regarding apotential association between products andreported symptoms or conditions. Adverseevents associated with product use arethought to be significantly underreported,because many consumers or health profes-sionals may not recognize a link between aparticular product use and an injury orillness, or they may not bother to register a

FINDINGS

The Commission considers it axiomatic thatall marketed dietary supplements should besafe. The manufacturer bears the primaryresponsibility for assuring the safety ofdietary supplements, both under the terms ofFDCA and under the requirements ofproduct liability (4,5). The Commissionsuggests that when health-related statementsare made for dietary supplements in the formof statements of nutritional support or healthclaims, the manufacturer or vendor bears anadded responsibility for assuring the safetyof the product. The Commission concludesthat while assurance of safety is primarily theresponsibility of the dietary supplementindustry, the Federal government shares theresponsibility to ensure that there areadequate guidelines on GMPs, proceduresfor alerting the public when safety problemsare detected, and procedures for recallswhen necessary.

The Commission believes that existingpostmarket surveillance systems could beimproved. There is no requirement in theUnited States for mandatory reporting ofadverse reactions to foods, including dietarysupplements, and the Commission is notrecommending such a requirement. How-ever, better use could be made of the reports



that are received under the voluntary dosage recommendations on product labels,systems. The Commission urges FDA, the and labels should direct consumers to useindustry the scientific community, and con- products only as recommended. A labelsumer groups to work together voluntarily warning should also be utilized by theto improve passive postmarketing surveil- manufacturers, as specifically authorized bylance systems, including adverse reaction DSHEA, when the need for a warning isreporting systems, to ensure that any safety indicated for the safe and effective use of theproblems that arise are identified and product by consumers. For example, if therecorrected promptly. is a documented need for a warning relating

Some members of the Commission hold that and no warning is being provided by theFDA has sufficient authority to take action manufacturer, the Commission suggests thatagainst supplements that are deemed unsafe FDA use its authority to require warningsbut has failed to use this authority effectively about exceeding label doses when there isin the case involving products containing possible risk of serious harm to consumersephedrine alkaloids. They hold that the who inadvertently or intentionally exceed theenactment of DSHEA did not affect the recommended dose. Commission membersagency’s authority to protect the public from recognize that safety hazards resulting fromunsafe products. Other Commission mem- improper use of physiologically and/orbers believe that FDA’s enforcement efforts pharmacologically active products at dosesagainst dietary supplements are diminished other than those recommended are notby provisions of DSHEA that place the limited to dietary supplements. FDA hasburden of proving the existence of a previously relied on warnings in dealing withsignificant or unreasonable risk on the issues of safety (102).agency. One member believes thatmanufacturers should have a legal obligation,enforceable by FDA, to substantiate thesafety not only of new dietary supplements,but also of existing products, particularlywhen there is a new statement of nutritionalsupport or a new recommendation forincreased dosage. This Commission memberalso believes dietary supplements that havenot been adequately tested for safety shouldbear a warning such as that required forcosmetics (119).

DSHEA limits the determination of safety tothe doses recommended on the label, eventhough harm may occur at higher levels andthere may be a risk of use at higher levels.The Commission concludes that consumersshould be provided with clear and adequate

to consumer abuse of a particular product,

GUIDANCE

! Manufacturers and the industry as awhole must fully accept the responsibilityfor assuring the safety of dietarysupplements and must take any actionnecessary to meet the expectationexpressed in DSHEA that dietary sup-plements are and will continue to besafe for use by the consuming public.

! The Commission urges FDA, theindustry, the scientific community, andconsumer groups to work togethervoluntarily to improve passive postmar-keting surveillance systems, includingadverse reaction reporting systems, toensure that any safety problems thatarise are identified and correctedpromptly.



! Ensuring the safety of supplementsincludes the need to provide adequateinformation and warnings to consumers.The Commission strongly suggests thatdietary supplement manufacturersinclude appropriate warnings in productinformation where necessary, as specif-ically permitted by DSHEA. In addition,manufacturers should recognize theneed to advise women who are preg-nant or breast-feeding to consult ahealth professional about supplementuse during the pre- and postnatalperiods.

! The Commission urges FDA to use itsauthority under DSHEA to take swiftenforcement action to address potentialsafety issues such as those posedrecently by products containing ephed-rine alkaloids. While it is expected thata responsible industry will avoid mar-keting unsafe products and that theindustry will react promptly to removeproducts shown to be associated withsignificant or serious adverse reactions,in the final analysis there must be astrong and reliable enforcement systemto back up the safety provisions ofDSHEA. Failure by FDA to act whenstrong enforcement is needed under-mines public confidence in the ability ofnot only the Federal government butalso the dietary supplement industry toensure safety and avoid harm to thepublic.

! FDA and, within many States, certainagencies have the responsibility inenforcement actions to develop, affirma-tively, evidence that shows anunreasonable risk from using existingsupplements. FDA and appropriateagencies in some States may needadditional resources to develop thenecessary evidence, and these agenciesneed to be given the resourcesnecessary to meet this important

responsibility in the context of theiroverall public health priorities.

LABEL INFORMATION

The Commission did not address specificallythe basic format for ingredient labeling andnutrition labeling. DSHEA mandated somechanges in FDA’s existing regulations onthese topics, and FDA proposed newregulations in December 1995 (40-43). Atthe time of the Commission’s first meeting inFebruary 1996, FDA was already in theprocess of receiving extensive comments onthose proposals from the affected industryand from other members of the public. Itwas anticipated that these labeling regula-tions would be amended based on the publiccomments and would be finalized before theCommission’s report was completed. Fur-ther, DSHEA’s primary mandate to theCommission in regard to labeling concernedclaims-related issues, which have been thefocus of the Commission’s efforts.

1. Label Format and Statement ofIdentity

Dietary supplements, like other foods, aresubject to certain mandatory labelingrequirements. Basic food labeling regula-tions, which apply equally to conventionalfoods and dietary supplements, are set forthin the Code of Federal Regulations (CFR)(97). These regulations define the principaldisplay panel (PDP) of a product, whichmust bear the name of the product and astatement of contents or net weight. Theinformation panel is defined generally as thepanel to the right of the PDP. It bears otherinformation required by regulation, such asthe ingredient list and nutrition labeling. Thename and address of the manufacturer,



packer, or distributor of the product mustalso appear on the label. DSHEA imposedsome special requirements for dietarysupplement labeling, including the require-ment that the term “dietary supplement”appear on the label.

2. Ingredient List

FDCA requires that food labels bear a list of regulations in 1941 (66) regarding theall ingredients, and FDA regulations require format and content of vitamin and mineralthat the ingredients be listed in descending labeling for nutritional supplements andorder of predominance by weight (103). fortified foods. Vitamins and minerals wereFDA exempted dietary supplements from to be listed in tabular form, with the name ofthis requirement in trade correspondence the nutrient, the quantity in metric units, and(66). As a result, dietary supplements his- a statement of the percentage of the MDRtorically have provided a table of nutrients, provided. The same regulations establishedas required by special dietary food regula- MDRs for several vitamins and minerals. Iftions, but did not always provide a separate substances were present in the product forlist of all ingredients, including excipients. which an MDR had not been established, an

DSHEA requires that all ingredients of a MDR” column, referring to a footnote thatdietary supplement be listed on the label, but stated: “Requirement in human nutrition notnot necessarily as part of a consolidated established.”ingredient list. Some ingredients may benamed in the nutrition label and need not be In 1973, after extensive proceedings, FDArepeated in a separate ingredient list. revised the special dietary use regulations

DSHEA also requires that, when a product agency also proposed a restrictive “standardincludes botanicals, the label indicate which of identity” for vitamin and mineral supple-part of the plant is used. FDA recently ments, which was ultimately overturned bypublished a final rule on regulations that the courts, invalidated in part by legislationwould require additional information about passed in 1976, and withdrawn by FDA inbotanicals, including the Latin binomial and 1979. The history of the vitamin and mineralan identification of the scientific authority for regulations is not discussed here, except tothe Latin name unless the botanical is listed note that the only significant provisionin Herbs of Commerce (68). remaining was one replacing the MDR with

3. Special Dietary Use Labeling andNutrition Labeling

FDCA requires that the label of a food Nutrition labeling was initiated by FDA as aintended for special dietary uses include: voluntary program in 1973 (64). Nutrition

. . . such information concerning itsvitamin, mineral, and other dietaryproperties as the Secretary determinesto be, and by regulations prescribes as,necessary in order fully to informpurchasers as to its value for such uses(Section 403(j)).

To implement this requirement, FDA issued

asterisk was to be used in the “Percent

and initiated nutrition labeling (64). The

the U.S. RDA as the label reference standardfor vitamin and mineral content forconventional foods and dietary supplements.



labeling was not mandatory unless a specifically authorizes three departures innutritional claim was made. However, if a dietary supplement labeling from theconventional food had nutrition labeling, nutrition labeling format applicable tothen the label was required to follow the conventional foods. format established by FDA. Dietary supple-ments were exempt from nutrition labeling ! DSHEA specifies that nutrition labelingbecause they were intended to be covered for dietary supplements shall not requireby special dietary use regulations. the listing of any substance not present in

NLEA required nutrition labeling of all foods conventional foods to list all “manda-and supplements and required FDA to tory” nutrients, even if the amountestablish an appropriate format (67). NLEA present is zero.also changed the general emphasis of ! DSHEA specifies that substances with-nutrition labeling to increase the focus on out a DV may be listed in dietarymacronutrients believed to have a major supplement nutrition labeling, followingpositive or negative impact on health. the list of nutrients with a DV. InFDA took the opportunity to develop an contrast, food labels cannot list anyentirely new and bolder format for nutrition substance in nutrition labeling exceptlabeling and replaced the U.S. RDA with a those for which a DV has beennew label standard for vitamins and minerals, established or which are specificallythe RDI. permitted by regulation.

FDA recognized the need for somewhat ! DSHEA permits dietary supplementdifferent formats for nutrition labeling of nutrition labeling to state the source of aconventional foods and nutritional supple- nutrient or other substance (e.g., niacinments. Final regulations on nutrition labeling as nicotinic acid). In contrast, foodfor conventional foods were promulgated in labels may list only the common name ofJanuary 1993. Final regulations on nutrition the nutrient (e.g., niacin), withoutlabeling for vitamin and mineral supplements mentioning the source compound withinwere issued in January 1994, prior to the the Nutrition Facts box. DSHEA alsopassage of DSHEA. No special provision provides that, if source compounds arewas made for botanical products, which listed in dietary supplement nutritionwould have been required to bear labeling, they need not be repeated in aconventional nutrition labeling. separate list of all ingredients.

DSHEA was passed in October 1994 with DSHEA requires implementation of itsprovisions that require revision of FDA’s labeling provisions by December 31, 1996,regulations on nutrition labeling for dietary but the procedures necessary for fullsupplements. DSHEA specifies that nutri- implementation were not completed by thattion labeling for dietary supplements be date. Final regulations were issued onprovided “in a manner which is appropriate September 23, 1997, and become effectivefor the product” and which is specified in on March 23, 1999 (26-28).FDA regulations. In addition, DSHEA

the product. In contrast, FDA requires



FINDING The Commission supports the informativelabel format mandated by DSHEA and urgesorderly implementation of appropriate reg-ulations.

NLEA CLAIMS IN DIETARYSUPPLEMENT LABELING

NLEA not only required mandatory nutritionlabeling for all foods including dietarysupplements but also defined “nutrientcontent claims” and established a process forapproval of “health claims.”

1. NLEA Nutrient Content Claims

NLEA requires that nutrient content claimsnot be used in food labeling unless the termsused have been defined by FDA and unlessthe terms are used in accordance with thosedefinitions. This provision came aboutbecause terms such as “low fat,” “highfiber,” and “no cholesterol” were believed tobe used in ways that were potentially mis-leading. FDA issued regulations imple-menting the requirement that nutrientcontent claims be defined (98). For the mostpart, the same nutrient content claimsallowed for foods are also allowed fordietary supplements. Nutrient content claim language allowed forboth foods and dietary supplements includesthe following:

! The terms “high in,” “rich in,” and “ex-cellent source of” may be used for nutri-ents on food and dietary supplementlabels provided the product contains 20percent or more of the DV per serving.

! The terms “good source,” “contains,”and “provides” may be used on foodlabels, provided the product contains 10to 19 percent of the DV of the nutrientper serving.

! Relative terms such as “more” and“added” may be used under specificconditions.

FDA regulations permit nutrient contentclaims for substances for which a DV hasbeen established. DSHEA specifically per-mits percentage nutrient content claims fordietary supplement ingredients for which aDV has not been established. This wouldallow a statement such as “twice the omega-3 fatty acids per capsule (80 mg) as in 100mg of menhaden oil (40 mg)” on a dietarysupplement label, even though no DV hasbeen established for omega-3 fatty acids(27).

2. NLEA Health Claims

In enacting DSHEA, Congress intended theCommission to address whether changesshould be made in the requirements forNLEA health claims for dietary supplements.Current FDA rules require the same type ofscientific evidence and support and the sameprocess for approval of NLEA health claimson dietary supplements as are required forconventional foods. DSHEA requires theSecretary to publish any recommendationsthe Commission makes with respect tochanges in the existing FDA regulationsconcerning NLEA health claims on dietarysupplements, along with a notice ofproposed rulemaking on such recom-mendations. In the absence of timely actionby the Secretary, dietary supplements will nolonger be subject to the requirements



applicable to health claims on conventionalfoods.

Historically, FDA had regarded health claimson foods as impermissible drug claims. In1987, FDA changed its policy, recognizedthe appropriateness of health claims onfoods, and proposed to develop guidelines orregulations regarding such claims (57).Under this rulemaking initiative,manufacturers would have needed tosubstantiate their health claims, but priorreview by FDA would not have beenrequired. What was sufficient for sub-stantiation became a heated issue in therulemaking process. As FDA developed itsproposed policies, manufacturers werealready making health claims for substancessuch as fiber, and some of these claimsprovoked public criticism and congressionaldebate, which led to the enactment ofNLEA.

The Commission is aware that challengeshave been brought on constitutional groundsto the provisions of NLEA concerning FDAapproval of health claims (91,92). A timedeadline for FDA action on final rules forhealth claims has been found necessary (92).The other provisions of NLEA have notbeen found to be invalid on constitutionalgrounds in the cases to date. The discussionof NLEA in this report is based on theprovisions in their present form.

NLEA defines health claims as statementsthat characterize a relationship between anutrient or food component and a specificdisease or health-related condition (100). Adisease or health-related condition:

. . . means damage to an organ, part,structure, or system of the body such

that it does not function properly (e.g.,cardiovascular disease), or a state ofhealth leading to such dysfunctioning(e.g., hypertension); except thatdiseases resulting from essentialnutrient deficiencies (e.g., scurvy,pellagra) are not included in thisdefinition (claims pertaining to suchdiseases are thereby not subject to . . .101.14 or 101.70).

NLEA requires that the standard of evidencefor health claims for conventional foods besignificant scientific agreement amongexperts qualified by scientific training andexperience to consider whether a claim issupportable. NLEA specified that healthclaims for dietary supplements would not besubject to that standard but instead would be“subject to a procedure and standard,respecting the validity of such claim,established by regulation of the Secretary”(FDCA 403(r)(5)(D). Numerous suggestionsfor alternative systems were made incomments on FDA’s proposed health claimsregulations. In promulgating regulations forhealth claims, FDA considered this issue andconcluded that the same standard andprocedure should apply to dietary supple-ments as to conventional foods (i.e., thereshould be a “level playing field” for healthclaims for all foods including supplements).

Significant scientific agreement is to bebased on the totality of publicly availablescientific evidence, including evidence fromwell-designed studies conducted in a mannerconsistent with generally recognizedscientific procedures and principles (99,104,107). FDA regulations for NLEA healthclaims define the types of substances that arepotentially eligible for specific health claimsand identify additional requirements formaking health claims.



Many of the diet-disease associations of Under NLEA, FDA was initially directed topotential relevance for health claims relate to review the evidence relating to 10 specificchronic disease processes for which diet is nutrient/disease relationships. In evaluatingone of many possible causes and which, for these initial candidates for health claims,both ethical and practical reasons, are often FDA contracted with Life Sciences Researchnot subject to direct experimentation. Thus, Office (LSRO), Federation of Americandifferent types of evidence are usually Societies for Experimental Biologyconsidered in attempting to establish that a (FASEB), for expert literature reviews andcausal association actually exists and that recommendations and FDA also soliciteddietary change would have preventive value. data from the public. Subsequently FDAWhere human experimentation is not approved eight health claims (five of theappropriate, other approaches are useful. original 10, plus three modifications of theFor example, an association may be inferred original 10). Two, omega-3 fatty acids andfrom a combination of epidemiological coronary heart disease as well as zinc andcomparisons or long-term observations of immune function in the elderly, were notpopulations exhibiting different dietary approved (Table 2).patterns, in vitro biochemical studies, andanimal studies. Where feasible and appro-pr- Two of the original 10 claims (those relatingiate, randomized controlled trials are con- to calcium and to folic acid) are approvedducted to establish the effects of dietary for use in dietary supplement labeling as wellmanipulations in human populations. as conventional food labeling. In evaluating

Commission members agree that a high birth defects, FDA convened an advisorystandard of evidence is appropriate for committee and was also strongly influencedhealth claims. A valid health claim may by the Public Health Service’s adoption of apromote behaviors that have a beneficial recommendation on this subject. The threeeffect on public health and, therefore, be modified claims relate to antioxidantassociated with effects on health care costs, vitamins and cancer, fiber and cancer, andquality of life, and productivity. fiber and coronary heart disease. FDA

Evaluating expert agreement is, by defini- per se but approved claims for food groupstion, a matter of judgment, and must rest on that are good sources of vitamin C, -a body of evidence considered adequate to carotene, or fiber.support such agreement (i.e., more thanpreliminary studies or a few emerging stud- For purposes of considering health claimsies, even if the evidence seems convincing). other than the 10 mentioned in NLEA, FDAGuidelines for selecting evidence for evalu- developed a petition process, as required byating a body of scientific evidence are NLEA, whereby a petitioner may request theincreasingly prominent in the scientific litera- establishment of regulations authorizing ature (11). The scientific literature also claim that characterizes the relationship of adescribes many processes for synthesizing nutrient to a disease or health-related condi-and evaluating a body of literature (1,13). tion (104). In considering such petitions,

the health claim for folic acid and neural tube

disapproved these claims for the substances

FDA indicated that manufacturers must



demonstrate that a product is safe when usedat the level needed to support a claim.

In response to petitions, three new healthclaims have been approved (Table 2), onefor sugar alcohols and reduced risk of dentalcaries (36) and one each for soluble fiberfrom whole oats and from psyllium husksand reduced risk of coronary heart disease(34,35). FDA did not take action on apetition for a health claim for calcium-richdairy products and reduced risk of hyper-tension (129). Health claims currentlyauthorized in 21 CFR are listed in Table 2.

For each of the approved health claims, FDAregulations include “model claims” that maybe used by manufacturers to assure that allcriteria for a claim are met. However,manufacturers are free to develop their ownclaims language, provided it meets thecriteria set forth by FDA.

Many food and dietary supplement manu-facturers complained that the health claimsrequirements initially established by FDAwere too cumbersome and that the modelclaims were not consumer friendly. Inresponse to petitions filed by the NationalFood Processors Association and theAmerican Bakers Association, FDA pro-posed in December 1995 to streamlinespecific requirements for health claims (44).These regulations are not yet final. Themodel calcium claims below illustrate thedramatic difference between FDA’s originalrequirements and the streamlined proposal:

Original: “Regular exercise and ahealthy diet with enough calcium helpsteen and young adult white and Asianwomen maintain good bone health andmay reduce their high risk ofosteoporosis later in life. Adequate

calcium intake is important, but dailyintakes above about 2,000 mg are notlikely to provide any additional benefit”(105).



Table 2

STATUS OF HEALTH CLAIMS

Approved Health Claims for Dietary Supplements and Conventional Foods

Calcium and osteoporosisFolate and neural tube defectsSoluble fiber from whole oats and coronary heart diseaseSoluble fiber from psyllium husks and coronary heart diseaseSugar alcohols and dental caries

Approved Health Claims for Conventional Foods Only

Dietary lipids and cancerDietary saturated fat and cholesterol and coronary heart diseaseFiber-containing grain products, fruits, and vegetables and cancerFruits and vegetables and cancer (for foods that are naturally a “good source” of vitamin A, vitamin C, or dietary fiber)Fruits, vegetables, and grain products that contain fiber, particularly soluble fiber, and coronary heart diseaseSodium and hypertension

Health Claims Not Authorized

Antioxidant vitamins and cancerDietary fiber and cancerDietary fiber and cardiovascular diseaseOmega-3 fatty acids and coronary heart diseaseZinc and immune function in the elderly



New: “Especially for teen and youngadult women, adequate calcium in ahealthful diet may reduce the risk ofosteoporosis later in life” (44).

When FDA proposed a health claim relatingto folic acid in 1993 (58 Fed. Reg. 53254),the original language was:

Original: “Women who consume ade-quate amounts of folate, a B vitamin,daily throughout their childbearingyears may reduce their risk of having achild with neural tube birth defect. Such birth defects, while not wide-spread, are very serious. They can havemany causes. Adequate amounts of and for dietary supplements. The Commis-folate can be obtained from diets rich infruits, dark green leafy vegetables andlegumes, enriched grain products,fortified cereals, or a supplement. Folate consumption should be limitedto 1,000 µg per day from all sources.”

In March 1996, FDA finalized a regulationstreamlining the model health claim relatingto folic acid:

New: “Healthful diets with adequatefolate may reduce a woman’s risk ofhaving a child with a brain or spinalcord birth defect” (37,106).

FINDINGS

The Commission recognizes that appropriateNLEA health claims made for dietarysupplements and foods may be an importantmethod of public education about dietarypractices that may have a positive influenceon health. The power of advertising andmarketing of products in connection withvalid health claims provides a means forpublic education that is difficult to providethrough other channels. For this reason, it isimportant that health claims be based on

results of a body of research that demon-strates that public health benefits can beachieved through this mechanism. A usefulconsideration of how evidence should beevaluated relative to diet and healthrelationships has been published by theCommittee on Diet and Health (13). Invalidhealth claims may increase costs toconsumers or result in health behaviors thatare not helpful or even have negativeconsequences to health and well-being.

The Commission supports the concept offairness, in which the requirements forNLEA health claims are the same for foods

sion believes that different health claimstandards for dietary supplements andconventional foods would be confusing toconsumers and would be poor public policy.The Commission considered the standardsfor scientific evidence and the proceduresrequired for health claim approval, includingthe question as to whether health claims forfoods and dietary supplements should beregulated in the same way. The Commissionconcluded that both the scientific standardsand the approval process for health claimsfor dietary supplements and for conventionalfoods should be the same. The Commissionagrees with the key aspects of the rules thatrelate to the formal standard for decisionmaking and believes these allow forflexibility in evaluating individual petitionsfor health claims.

Some Commissioners expressed concernabout the current FDA review process forNLEA health claims. The Commissionsuggests that the process whereby FDA



determines whether significant scientificagreement exists for support of a specifichealth claim could be improved. Forexample, there could be greater use of FDA-sponsored conferences or workshops onissues related to health claims of specificsubstances, such as those held on antioxi-dants, cancer, and cardiovascular disease(53). In particular, FDA should considergreater involvement of scientists outside ofFDA, including scientists in other govern-ment agencies, in the review process. Theagency should develop criteria for selectingreview panels external to FDA that would beconsidered scientifically qualified, balanced,reliable, and independent. TheLSRO/FASEB panels used by FDA provideone example of appropriate outside review.

Recommendations by such outside panelswould not have presumptive weight in theapproval process, but submission of evidencefrom such a review by petitioners shouldstrengthen the petition and expedite thereview process. The agency would beexpected to provide an explanation of anydisagreement with such a review panel,given the panel’s expertise. Although theviews of other governmental agencies shouldnot substitute for the authority of FDA, theyshould be given serious consideration, andthey are important in considering whethersignificant scientific support for a claimexists. FDA and other agencies need to becontinually aware that the public may beconfused by disparate recommendations ofgovernmental public health agencies inrelation to food or dietary supplements.

GUIDANCE

! The process for approval of healthclaims as defined by NLEA should

remain the same for dietary supple-ments and conventional foods.

! The standard of significant scientificagreement is appropriate and serves thepublic interest. The standard ofsignificant agreement should not be sostrictly interpreted as to require unani-mous or near-unanimous support.

! FDA should ensure that broad input isobtained to ascertain the degree ofscientific agreement that exists for aparticular health claim. The use ofappropriate panels of qualified scientistsfrom outside of the agency isencouraged, and the views of othergovernment agencies should be givenconsiderable weight in determiningwhether significant scientific agreementexists.

SCOPE OF STATEMENTS OFNUTRITIONAL SUPPORT

DSHEA allows a dietary supplement label tobear a statement of nutritional support whenthe statement:

(1) Claims a benefit related to a classicalnutrient deficiency disease;

(2) Describes the role of a nutrient or dietaryingredient intended to affect structure orfunction in humans;

(3) Characterizes the documented mechan-ism by which a nutrient or dietaryingredient acts to maintain structure orfunction; or

(4) Describes general well-being fromconsumption of a nutrient or dietaryingredient.

Statements of nutritional support relating tothe structure and function of the body (2 and3 above) are typically called “structure/



function” statements of nutritional support. (i.e., a statement that is not a health claimThese are nearest in usage to the types of and not a drug claim) has not been specifi-statements that otherwise might be con- cally outlined in either legislation orsidered to be health claims or drug claims. regulations. While some members believe

Statements linking foods or nutrients with disease prevention, at least one membergrowth, health, and well-being (that is, with believes that statements of nutritional sup-human structure or function but not with a port may neither expressly nor implicitlyspecific disease or dysfunction) historically claim such usage.have been permitted on foods. The FDCA indirectly addresses structure/function state- Commission members agree that claims forments by defining drugs as “articles (other dietary supplements that meet the definitionthan food) intended to affect the structure or of health claims, as defined under NLEA,any function in the body of man or other should continue to be regulated under theanimals.” The statement that “calcium builds same NLEA provisions that apply tostrong bones and teeth” is a classic example conventional foods. It can be difficult,of an allowable structure/function statement however, to clearly distinguish an allowableof nutritional support for foods. structure/function statement of nutritional

DSHEA specifically creates a category of an unauthorized health or drug claim. Thestatements of nutritional support, including Commission reviewed approximately 1,000structure/function statements, to ensure that statements of nutritional support referencedsuch information will be permitted for in notification letters submitted to FDA.dietary supplements. Nutritional support Based on this review, the Commissionstatements, and especially structure/function concluded that the lack of definition of thestatements, have become more visible since clear boundaries of these statements leavesthe passage of DSHEA and are subject to many uncertainties as to what actuallyunique requirements for notification and for constitutes a legitimate statement ofspecial labeling. DSHEA requires that the nutritional support in the context of dietarymanufacturer notify FDA within 30 days supplements. after the first use of a nutritional supportstatement, that the manufacturer have Commission members expressed concernsubstantiation for the statement, and that the that some statements of nutritional supportlabel include the following disclaimer: being made are in fact more akin to drug

This statement has not beenevaluated by the Food and DrugAdministration. This product isnot intended to diagnose, treat,cure, or prevent any disease.

What constitutes an allowable structure/function statement of nutritional support

statements of nutritional support may imply

support from one that might be considered

claims. Commission members who weretroubled about the wording of structure/function statements suggested that the mostproblematic wording is seen in statementsostensibly relating to “normal healthyfunction” that actually imply the need toremedy an underlying abnormal or un-healthy state and statements mentioningorgans (e.g., heart, liver, and prostate) or



systems (e.g., circulatory) associated with These Commissioners believe that thismajor clinical conditions. position needs reconsideration in light of

The Commission was divided on the statement of nutritional support regardingdistinction between DSHEA-allowable the maintenance of healthy blood choles-structure/function statements and drug terol levels that is a statement of nutritionalclaims for claims referring to organs. Some support and not a health claim or drugCommission members believed that such claim. In a similar manner, FDA historicallystatements were either drug claims or has been sensitive to label statementsNLEA health claims. It was noted that, for relating to immune function on the groundshealth claims, FDA has defined a disease or that they are implicit or explicit claimshealth-related condition to include damage relating to acquired immune deficiencyto an organ, part, or structure of the body syndrome (AIDS). While a statement ofso that it does not function properly (99). nutritional support should not be such thatSome Commission members believe that the it could be interpreted as a direct or indirectpotential for allowing these types of AIDS claim, some Commission membersstatements for dietary supplements is a believe it should be possible to makefundamental flaw of DSHEA, creating a legitimate statements of nutritional supportloophole for quasi-drug claims. Others about substantiated effects on immunesuggest that the ability to make such function or disease resistance.statements is implicit in DSHEA and thatthere is emerging scientific evidence for Statements of nutritional support thatcertain foods and other dietary ingredients mention an acute effect on the structure orhaving benefit for specific organs or function of a major system (e.g., reducesfunctions of the body. These members of heart rate) raise particular concern for somethe Commission noted that these provisions Commission members. In contrast, effectsof DSHEA were written with the explicit on stress, mental acuity, or bone or skingoal of making such information available health within the normal range seemed toto the public. carry less serious connotations. However,

Statements of nutritional support relating to stress and mental acuity claims andstructure or function should not be used to emphasize that these and all statementsimply effects that are currently considered related to structure and function of theprescription drug claims. For example, oral body need to be carefully evaluated on ancontraceptives alter physiological function, individual basis. One important concernbut a contraceptive effect is inappropriate relates to safety, that is, the potentialas a statement of nutritional support. seriousness of any effect that might extend

Some Commission members noted that ability to recognize the range of normalityprior to DSHEA, FDA took the position is also an issue. One member believes thatthat virtually any statement relating to to be an appropriate statement of nutritionalcholesterol would be interpreted as a claim support, a statement would need to identifyrelating to the prevention of heart disease. a dietary relationship for the supplement.

DSHEA and that it is possible to craft a

some members still have concerns about

beyond the normal range. The consumer’s



FINDINGS

The Commission has developed guidelinesas to what constitutes an acceptable state-ment of nutritional support of the structure/function type. These guidelines are listedbelow as Commission policy guidance. TheCommission considers that statements ofnutritional support should provide infor-mation that can help consumers makeinformed choices about their health. Inkeeping with DSHEA, the statement shouldnot be false or misleading and shouldprovide scientifically valid information tothe consumer. Also, the product should besafe under conditions of intended use.

Analysis by the Commission of FDA’sresponses to notification letters indicatesthat the agency has not objected specificallyto statements that are consistent with theguidelines the Commission recommends,but FDA has also made it clear that theabsence of an objection by the agency doesnot indicate acceptance of the appropri-ateness of the claim (128). The provision ofearly guidance by FDA to manufacturers be a claim to “restore” normal bloodmaking statements of nutritional support isappropriate and helpful in clarifying theappropriate scope of these statements.

GUIDANCE

! While the Commission recognizes thatthe context of a claim has to be con-sidered on a case-by-case basis, theCommission proposes the followinggeneral guidelines:

1. Statements of nutritional supportshould provide useful information toconsumers about the intended useof a product.

2. Statements of nutritional supportshould be supported by scientifi-cally valid evidence substantiatingthat the statements are truthful andnot misleading.

3. Statements indicating the role of anutrient or dietary ingredient inaffecting the structure or function ofhumans may be made when thestatements do not suggest diseaseprevention or treatment.

4. Statements that mention a bodysystem, organ, or function affectedby the supplement using termssuch as “stimulate,” “maintain,”“support,” “regulate,” or “promote”can be appropriate when thestatements do not suggest diseaseprevention or treatment or use for aserious health condition that isbeyond the ability of the consumerto evaluate.

5. Statements should not be madethat products “restore” normal or“correct” abnormal function whenthe abnormality implies the pres-ence of disease. An example might

pressure when the abnormalityimplies hypertension.

6. Health claims are specificallydefined under NLEA as statementsthat characterize the relationshipbetween a nutrient or a foodcomponent and a specific diseaseor health-related condition. State-ments of nutritional support shouldbe distinct from NLEA health claimsin that they do not state or imply alink between a supplement andprevention of a specific disease orhealth-related condition.

7. Statements of nutritional supportare not to be drug claims. They



should not refer to specific diseases,disorders, or classes of diseases andshould not use drug-related terms such as“diagnose,” “treat,” “prevent,” “cure,” or“mitigate.”

! To the extent resources permit, FDAshould continue to provide guidance to should be a requirement that a notificationmanufacturers by responding to lettersof notification when the agency deemsa proposed statement to be inappro-priate as a statement of nutritionalsupport.

NOTIFICATION LETTERS FORSTATEMENTS OF NUTRITIONALSUPPORT

DSHEA requires that the manufacturer ofa dietary supplement bearing a statement ofnutritional support notify the Secretary nolater than 30 days after the first marketingof the dietary supplement that such astatement is being made. The law alsostates that the manufacturer must havesubstantiation that the statement is truthfuland not misleading. The law does notprovide that the evidence supporting astatement be reviewed by a regulatoryagency prior to marketing of the product.Presumably the evidence substantiating astatement would be examined only if achallenge to the labeling or advertising weremade.

FINDINGS

The Commission believes that guidelinesare needed for standardizing the format andcontent of the notification letters. Inkeeping with the intent of DSHEA, whichis to provide consumers with truthful, notmisleading, and scientifically valid informa-tion to make informed health care choices,the Commission suggests that the

notification letters and the FDA responsescontinue to be made available in the publicdockets at FDA (Docket Nos. 97S-0162and 97S-0163).

The Commission considered whether there

letter include a summary of the evidencesupporting the statement of nutritionalsupport and the safety of the product. Thiswas an effort by the Commission to fulfillits mandate in DSHEA to “evaluate howbest to provide truthful, scientifically valid,and not misleading information to con-sumers so that such consumers may makeinformed and appropriate health carechoices for themselves and their families.”Although DSHEA does not require that asummary of the data supporting statementsof nutritional support be submitted to FDAwith the notification letters, a majority ofthe Commission members favored sucha requirement. Some members of theCommission saw major problems with sucha recommendation because it would imposea requirement not specified in DSHEA.Further, some Commissioners were con-cerned that the summary might allow orrequire public display of information thatmakes or implies an unintended claim,thereby putting a company at risk ofenforcement action for making an imper-missible statement of nutritional supportbecause of the nature of the evidence orpublications cited. Also, there was somequestion whether FDA has legal authorityto require a summary of the evidence in thenotification letter.

The Commission recommended in its June1997 draft report that the letter of notifica-tion include a summary of the evidencesupporting both benefit and safety. There



was considerable opposition to this recom- This language is consistent with themendation in the public comments on the provisions of DSHEA that state that adraft report. Industry representatives ob- product will be considered “adulterated”jected to a requirement that goes beyond (unsafe) if it presents a significant orthe specific provisions of DSHEA, and unreasonable risk of illness or injury undersome nutrition professionals, public health the conditions of use recommended orofficials, and consumer groups objected to suggested in the labeling.the public availability of a summary of theevidence because of the potential for Based on the public comments on the draftconfusion when that summary had not been report, the Commission deleted the recom-approved by FDA. In response to the mendation that a consumer summary of thecomments, the Commission has amended its evidence for safety and benefit be submittedrecommendation to omit the requirement as part of the letter of notification.that a summary of evidence supporting both However, the Commission believessafety and benefit be submitted in the letter consumers need balanced, nonmisleading,of notification. and valid information regarding the evi-

However, the Commission urges that Chapter IV of this report.manufacturers voluntarily include anaffirmation in the notification letter or in a The Commission recognizes that FDAseparate public notice, indicating that the recently published its final rule outliningcompany has reviewed the evidence the information that should be contained insupporting the statement of nutritional a letter of notification (30) (see Endnote 1).support and has concluded that it is The Commission prefers that the notifica-truthful, not misleading, and scientifically tion letter contain more information thanvalid. DSHEA requires that manufacturers FDA has required:have evidence that a statement is truthfuland not misleading. DSHEA charges theCommission to make recommendations forproviding consumers with information thatis scientifically valid. Therefore, all three ofthese criteria need to be reflected in theaffirmation.

Also, the Commission suggests thatmanufacturers include an affirmation in thenotification letter or other public notice thatthey have evaluated the available infor-mation relating to safety and have satisfiedthemselves that the product does notpresent a significant or unreasonable risk ofillness or injury under the conditions of userecommended or suggested in the labeling.

dence. These issues are addressed further in

Statement of Purpose: An indication thatthe purpose of the letter is to providenotification of a statement of nutritionalsupport, including the exact wording thatappears on the label.

Vendor Information: The name, address,and telephone number of the manufacturerand, if available, the address and/or toll-freetelephone number for consumer inquiries.

Product Identification: The name anddescription of the product should includethe trade name and the common or usualname. A copy of the product label (or label



copy, if labels are not yet printed) should be ! Notification letters should continue toincluded.

Ingredient Statement: The specificindividual ingredients or combination ofingredients for which the statement ofnutritional support is made should beidentified. For botanicals, ingredientsshould be identified by the common orusual name, the Latin binomial and itsscientific authority, and the part(s) of theplant used. Some Commission membersbelieve that many botanicals are adequatelyidentified by common name, and thatscientific nomenclature should be requiredonly when confusion or misidentificationmight occur.

Intended Use: The statement of intendeduse should include the recommendeddosage, and appropriate contraindicationsor warnings must be stated. the common or usual name. A copy

Statements of Affirmation: The Commis-sion suggests that, in the notification letteror in a separate public notice, manu-facturers should affirm that they haveevaluated the evidence on safety andbenefit. That is, the manufacturer shouldaffirm that there is supporting evidence thatthe statement of nutritional support istruthful, not misleading, and scientificallyvalid. The manufacturer should also affirmthat the product does not present asignificant or unreasonable risk of illness orinjury under the conditions of use recom-mended or suggested in the labeling.Manufacturers also need to comply with theFDA final rule on the contents ofnotification letters (30).

GUIDANCE

be available in the public dockets.

! While the rulemaking process need notbe reopened at this time, theCommission suggests that notificationletters should include the followinginformation:

1. A statement that the purpose of theletter is to provide notification of astatement of nutritional support,including the exact wording thatappears on the product label.

2. The name, address, and telephonenumber of the manufacturer ordistributor, and if available, theaddress and/or toll-free telephonenumber for consumer inquiries.

3. The name and a description of theproduct. The name of the productshould include the trade name and

of the product label or label copy, iflabels are not yet printed, should beincluded.

4. The identity of specific individualingredients or combinations ofingredients for which the statementof nutritional support is made. Forbotanicals, ingredients should beidentified by the common or usualname, the Latin binomial and itsscientific authority, and the part(s)of the plant(s) used.

5. A statement of intended use,including the recommended dosageand appropriate contraindicationsor warnings.

! In the notification letter or in a separatepublic notice, manufacturers shouldprovide statements of affirmation thatthey have substantiation for thestatement of nutritional support and



that the product does not represent asignificant or unreasonable risk of illnessunder conditions of use recommended orsuggested in labeling.

! Although some of the informationindicated in the above guidelines is notrequired by FDA, the Commissionsuggests that manufacturers use theseguidelines in preparing their notificationletters.

SUBSTANTIATION FILES FORSTATEMENTS OF NUTRITIONALSUPPORT

During its public hearings, the Commissionwas asked by several manufacturers toprovide guidance regarding the type ofinformation that a responsible vendorshould have to substantiate a statement ofnutritional support.

The law does not define “substantiation,”and the Commission has considered guide-lines as to what constitutes appropriatedocumentation for a statement of nutritionalsupport. Following appropriate guidelinesfor substantiation could allowmanufacturers to have more confidence thata statement will be sustained if challengedby regulatory agencies. Following theguidelines would increase the likelihoodthat statements will be appropriatelysupported and would provide consumerswith some basis for judging the soundnessof the statements that are made.

Statements of nutritional support asallowed under DSHEA must be substanti-ated by evidence that the statements are“truthful and not misleading.” The evidenceneeded to substantiate statements ofnutritional support will vary depending onthe statement made. For example, state-ments about the relation of a vitamin ormineral to a classic nutrient deficiencydisease are generally supported by asignificant body of research. DSHEArequires that statements claiming a benefitrelated to a classic nutrient deficiency



disease disclose the prevalence of the and the reliability of the scientific evidencedisease in the United States. The Com- and the level of support among scientistsmission concurs that the data on prevalence that experts would find necessary. Underin the U.S. population should come from general principles for substantiation ofrecognized sources, such as the several claims (25), consideration is also given tosurveys that are components of the National factors such as the type of claim, theNutrition Monitoring and Related Research product, the consequences of a false claim,Program, the publications derived from this the benefits of a truthful claim, the cost ofprogram, or publications in peer-reviewed developing substantiation for the claim, andjournals. the amount of substantiation experts in the

Other types of statements of nutritional expert testimony and consumer surveys aresupport may be substantiated by various useful in determining what level oftypes of evidence, including historical substantiation consumers expect to supportusage, animal testing, in vitro studies, a particular product claim and the adequacyepidemiologic data, and human studies. of the evidence an advertiser possesses. TheControlled clinical studies represent Commission finds that substantiation forimportant evidence to support a claim, statements of nutritional support willprovided the studies have been well likewise vary depending on the nature ofdesigned. While proprietary studies can be the statement being made, the healthimportant, studies published in peer- importance of the statement, and thereviewed scientific journals have added difficulty of conducting experimentalcredibility. Substantiation files should studies.include key data, including evidence fromstudies showing no benefit or adverse The Commission discussed how a statementeffects. The weight of evidence should of nutritional support can be adequatelysubstantiate the statement of nutritional substantiated when it is based solely onsupport. historical use without supporting

The Commission recognizes that the mum, such a statement of nutritionalcontent of the substantiation file may be support would have to be carefully quali-developed by parties other than the manu- fied to prevent misleading consumers.facturer or vendor of the finished product, Some Commission members believe that, insuch as an ingredient supplier, a private some circumstances, qualified statementslabel manufacturer, a trade association, or based solely on historical use would bean external consultant. recognized by experts as being adequately

The Commission considered the criteria that experts would want more scientificthat FTC has established regarding support support for substantiation and especially soof food advertising claims (24). In deter- in the case of statements that havemining whether a reasonable basis exists for particular health importance. Onean advertising claim, such as an unqualified Commissioner believes that scientifichealth claim, FTC evaluates the competency

field believe is reasonable. In addition,

experimental or clinical data. At a mini-

substantiated. Other Commissioners believe



support for substantiation is needed for all active principle(s) in the productstatements with health importance. responsible for the effect should be

DSHEA does not require that substanti-ation files be made available to FDA, andthe majority of the Commission membersare not recommending a change in legisla-tion regarding the availability of these files.However, one member believes that FDAneeds to be able to obtain access to therelevant files of a manufacturer to enforceeffectively the manufacturer’s obligation tosubstantiate statements of nutritional sup-port and the obligation to substantiatesafety. That member believes the authorityto obtain access to substantiation filesshould be provided either through a rulesimilar to that proposed by FDA on nutri-ent content claims based on new technologyfor food ingredients (38) or throughlegislative action.

In the Commission’s public hearings, anumber of witnesses indicated that guidanceregarding the content of the substantiationfile is needed. The Commission hasdeveloped the following guidelines on thecontent of substantiation files.

Notification Letter: A copy of thenotification letter should be included.

Identification of Dietary SupplementIngredients: The identity and quantity of and the file should indicate the basis of thethe dietary supplement ingredient(s) that is manufacturer’s conclusion that the product(are) the subject of the statement of can reasonably be expected to be safe atnutritional support should be included. If levels of intended use.possible, the active component and mechan-ism of action should also be indicated. Inthe case of individual chemical compounds,such as vitamins and minerals, the specificcomponents are readily identified; in thecase of botanicals or animal products, the

identified, where known.

Evidence to Substantiate Statements ofNutritional Support: Such evidence shouldinclude copies of key references toexperimental or clinical data and/or findingsof authoritative bodies and other evidence,where appropriate. References shouldinclude relevant information, positive ornegative. Research or monographs fromappropriate foreign sources may be cited,along with evidence that specific uses orclaims are approved in other countries. Aninterpretive synopsis by an individual(s) orgroup qualified by training and experienceto evaluate the evidence should accompanythe literature citations and should assessclearly the evidence supporting thestatement. Evidence for efficacy shouldinclude the dosage at which effects areobserved. Where historical use is cited asthe evidence for a statement, thecomposition of the product shouldcorrespond with the material for which suchclaims of historical use may be made. Thecomplexity of a product may affect thesubstantiation required.

Evidence to Substantiate Safety: TheCommission believes safety is of primaryconcern in marketing dietary supplements,

Good Manufacturing Practices: Assur-ance that GMPs were followed in themanufacture of the product should beindicated.



Qualifications of Reviewers: Thequalifications of those who reviewed theevidence should be included. Substantia-tion should be assembled by an individual(s)or group qualified by training andexperience to assess the evidence, and thefile should list the qualifications of thosewho reviewed the data on safety andefficacy. If an external advisory body wasconsulted, it should be identified.

The Commission provides the followingguidance regarding the information aresponsible manufacturer should have in asubstantiation file for a statement ofnutritional support and product safety.While the Commission’s guidance onsubstantiation files is directed to statementsof nutritional support and safety, othertypes of label statements may be made fordietary supplements. The Commission’sguidance on substantiation file content maybe helpful in identifying what a responsiblemanufacturer would do for substantiation ofother types of label statements.

GUIDANCE

! Substantiation files for statements ofnutritional support and safety shouldinclude the following information:

1. A copy of the notification letter.

2. The identity and quantity of thedietary ingredient(s) that is (are)the subject of the statement ofnutritional support.

3. The key evidence to substantiatestatements of nutritional support,including an interpretive summaryof the evidence by an individual(s)or group qualified by training andexperience.

4. Evidence substantiating the safetyof the product.

5. Assurance that good manufacturingpractices were followed in themanufacture of the product.

6. The qualifications of the indi-vidual(s) or group who reviewed theevidence for safety and efficacy.

PUBLICATIONS EXEMPT FROMCLASSIFICATION AS LABELINGWHEN USED IN CONNECTIONWITH SALES

Historically, FDA has considered literatureused directly in connection with the sale ofa product to be “labeling” for the product.Section 5 of DSHEA exempts certainpublications used in connection with thesale of dietary supplements from beingdefined as “labeling.” The exemptionapplies to “a publication, including anarticle, a chapter in a book, or an officialabstract of a peer-reviewed scientificpublication that appears in an article andwas prepared by the author or the editors ofthe publication, which is reprinted in itsentirety . . . .”

DSHEA directs the Commission to studyand make recommendations for the regula-tion and evaluation of label claims andstatements for dietary supplements, specifi-cally “including the use of literature inconnection with the sale of dietary supple-ments.”

DSHEA has only a brief official legislativehistory, and one of the few points it coversreiterates that the labeling exemption “doesnot apply to a summary of a publicationother than an official abstract of a peer-



reviewed scientific publication” (see End- scientific publications in drafting thisnote 2). DSHEA exempts a publication labeling exemption. However, the termfrom “labeling” only if it: “publication” as used in this section is not

(1) is not false or misleading;(2) does not promote a particular

manufacturer or brand of a dietarysupplement;

(3) is displayed or presented, or isdisplayed or presented with othersuch items on the same subjectmatter, so as to present a balancedview of the available scientificinformation on a dietarysupplement;

(4) if displayed in an establishment, is tant of the five requirements outlined inphysically separate from thedietary supplements; and

(5) does not have appended to it anyinformation by sticker or any othermethod.

DSHEA specifies that this provision “shallnot apply to or restrict a retailer orwholesaler of dietary supplements in anyway whatsoever in the sale of books orother publications as a part of the businessof such retailer or wholesaler.” Further,DSHEA provides that in any proceedingbrought under this provision, the govern-ment shall bear the burden of proof “toestablish that an article or other such matteris false or misleading.”

The Commission finds that some of theserequirements of Section 5 of DSHEA aredifficult to apply. The emphasis on the needto reprint the publication “in its entirety,”the care given to describing an officialabstract of a scientific publication, and theprohibition against the use of any summaryother than the official abstract of a peer-reviewed scientific publication all suggestthat Congress was referring primarily to

restricted to a scientific publication and thuswould appear to apply to almost anypublication about the available scientificinformation on a dietary supplement,provided that the five additional require-ments noted above are met. This matteralso raises a concern about violation ofcopyright laws applicable to publishedarticles.

The Commission believes the most impor-

Section 5 of DSHEA is the requirementthat the publication itself be balanced orelse be displayed with other publicationsthat taken together provide a balanced viewof the available information. Determiningwhen a balance exists may be difficult, butthe concept itself is straightforward andincludes a need to acknowledge negative aswell as positive data and to indicate whichposition is supported by the weight of theevidence.

Well-written scientific review articlesgenerally are balanced, in that theyacknowledge both the positive and negativefindings on a given topic, but scientificreview articles are unlikely to be consumerfriendly. The same applies to scientificarticles reporting on original research. Theintroduction or the discussion sectiongenerally will note previous articles thatreported findings consistent with orcontrary to the new findings. However,scientific articles and perhaps especially theofficial abstracts of such articles may bedifficult for the consumer to understand.Therefore, it appears likely that the bulk ofthe literature used in accordance with this



provision may be in the form of publications displayed in a location separate from thespecifically prepared for this purpose and dietary supplement. Apparently it may alsowritten for the consumer. Some be provided in other instances, includingCommissioners believe that providing a direct sales (person-to-person sales), andbalanced view of scientific information some suggest it may even apply to mailprovided by positive and negative publi- order sales (7).cations used in connection with salespresents particular difficulties. Further DSHEA requires that the literature “notstudy is needed to determine whether there promote a particular manufacturer or brandare adequate and reliable means to ensure of a dietary supplement.” The Commissionthat a balanced view is provided. has considered what constitutes promotion

Several organizations are currently publish- in the case of a scientific article, theing materials specifically intended as “third- “methods” section of the article mayparty literature,” the term often used within identify a product that was used in thethe industry to refer to literature covered by study and donated by the manufacturerthis section of DSHEA. This literature can (69). In the view of the Commission, theprovide useful information for consumers, practice of donating products for researchprovided it meets all of the requirements of studies or directly supporting research onDSHEA, including the requirements that dietary supplements should be encouraged,the information be truthful, not misleading, and the mere mention of the identity of aand balanced. The Commission encourages product in a scientific article should not bemanufacturers, distributors, and others to viewed as “promotion” of that product. Ifprovide reliable information to help mention of the product in this context wereconsumers use dietary supplements viewed as promotion, then all manu-appropriately, whether that information is in facturers other than the one that providedthe form of “third-party literature” or in the the material would be free to use the articleform of labeling provided by the as “third-party literature.” This would notmanufacturer for inclusion on or with the appear to be a reasonable outcome. How-product. One member believes that the ever, this may be a moot point because, aspublications exempted from labeling should mentioned above, the full text of a scientificbe independent and should not be written, article seems unlikely to be used directly fordeveloped, or funded by the manufacturers consumer information.or sellers of dietary supplements, apart fromany support they provide for the underlyingscientific research.

There is uncertainty regarding the scope ofthe circumstances under which literaturemay be provided to consumers under thelabeling exemption. It is clear fromDSHEA that such literature may beprovided in the retail setting, provided it is

for purposes of this section. For example,

FINDING

The Commission supports the provision ofbalanced, truthful information to consumersregarding the uses of dietary supplements.The literature provision of DSHEA shouldbe used with care, strictly observing the fiverequirements pertaining to such literature.



GUIDANCE

! Because more experience with theimplementation of this provision mayprovide additional information about theuse of publications in connection with asale, the Commission suggests thatproactive monitoring of practice in thisarea be undertaken by FDA asresources permit and that regulatoryguidance be developed if necessary.

BOTANICAL PRODUCTS

Botanical products represent a majorcategory of permissible ingredients ofdietary supplements, but they also are usedas conventional foods, culinary adjuvants,and drugs. In the United States, the highest-volume use of botanicals is undoubtedly asfoods. This includes such staples of theU.S. diet as potatoes, tomatoes, corn,wheat, oats, rice, leafy greens, carrots,onions, and garlic. Many plants are alsoused as spices and flavorings. FDA regula-tions list approximately 250 botanicalingredients (and their essential oils andextracts) that are generally recognized assafe (GRAS) for use in foods as spices andflavorings, essential oils, and natural extrac-tives (110-113). In addition, more than 100are listed as approved flavoring agents foruse as natural flavorings in foods andbeverages (109).

In many countries, botanical remedies are amajor component of the pharmacopeia ofavailable medicinals. The Commission isaware that 80 percent of the world’spopulation relies mainly on health caresystems that include the use of plantextracts or their active ingredients (2).Further, many developed and developingcountries have established regulatory

systems covering the recognized preventiveand therapeutic uses of botanical remedies(70). The United States is a notableexception.

1. Statements of Nutritional Support

When marketed as dietary supplements,botanical products are permitted to bearstatements of nutritional support in thesame manner as all dietary supplements.After reviewing letters of notificationsubmitted to FDA, the Commission con-cluded that in many cases, a statement ofnutritional support may be adequate toinform consumers of the appropriate use ofa specific botanical product. However, theCommission also concluded that manybotanicals now are being labeled withstatements of nutritional support thatsuggest only indirectly the type oftherapeutic use that is traditional for theproduct. In such cases, the Commissionquestions whether the statement of nutri-tional support is adequate to convey toconsumers the intended use of the product.

For example, Figures 2 and 3 comparestatements related to the uses of echinaceaand ginger, respectively, in draft WHOmodel monographs (140) with statementsof nutritional support from notificationletters received by FDA. Most Commis-sioners believe that there are instanceswhen statements concerning treatment suchas those found in the WHO model mono-graphs may be more informative toconsumers than the less specific languageused in some of the statements of nutri-tional support.

2. NLEA Health Claims



Botanical products, as dietary supplements,are theoretically eligible for the FDA-approved NLEA health claims, provided allof the requirements for health claims can bemet. The Commission is not aware that anypetition has been filed with FDA to requestapproval of an NLEA health claim for anybotanical, except those used primarily asfoods. For example, a health claim forsoluble fiber from whole oats was approvedin January 1997 and amended in May 1997to include psyllium husks containingsufficient levels of naturally occurring -glucan to help lower cholesterol and thusreduce the risk of coronary heart disease(34,35).

In practice, some botanical products mayhave difficulty meeting the requirements foreligibility as NLEA health claims as setforth in the statute and 21 CFR 101.14(99). For example:

1. The product may not meet the requirement of providing aroma, taste,or nutritive value.

2. The ingredient(s) may not meet otherrequirements established in regulationsimplementing NLEA, including therequirement that use of the ingre-dient(s) “at the levels necessary tojustify a claim has been demonstratedby the proponent of the claim, toFDA’s satisfaction, to be safe andlawful . . .” (101).

3. The product claim may not relate to a“risk of disease or health-relatedcondition that is diet related, takinginto account the significance of thefood in the total daily diet . . .” (FDCASection 403(r)(3)(A)(ii)).

4. The evidence supporting the healthclaim may be based on historical userather than current scientific studiesand thus may not meet the test of“significant scientific agreement.”

The Commission suggests that NLEAhealth claims be permitted for botanicalproducts where appropriate but recognizesthat NLEA health claims will not cover alluses of such products, especially when theuse is not diet related or relates to an acutecondition or to treatment.

3. Regulation of Botanical Products inOther Countries

Several references regarding the regulationin other countries of botanical products formultiple uses were submitted to and re-viewed by the Commission (8,70,137).Botanical pharmacopeias have been estab-lished by a number of countries, includingGermany, France, the United Kingdom, andJapan. Systems of regulation applicable totherapeutic uses of botanical remedies havebeen established by the aforemen-



Figure 2

ECHINACEAE PURPUREAE

WHO Model Monograph

“11.1 Uses supported by clinical data.

Herba Echinaceae is administered orally as an immunostimulant, in supportive therapy for coldsand infections of the respiratory and urinary tract (1,3,5,7,8,18). Beneficial effects in the treatment ofthese infections are generally thought to be brought about by stimulation of the immune response(3,5,7). The term ‘supportive therapy’ denotes that Echinacea would ordinarily be administeredtogether with other antibacterial agents, such as antibiotics or sulfa drugs (1).

External uses include: promotion of wound healing, and inflammatory skin conditions (1,5,7,8,9,19). Echinacea preparations are used in topical applications for the treatment of chronic superficialwounds and skin inflammations (3,5,7,19).

11.2 Uses described in pharmacopoeias and in traditional systems of medicine.

None.

11.3 Uses described in folk medicine, not supported by experimental or clinical data.

Other medical uses claimed for Echinacea preparations include treatment of yeast infections, sideeffects of radiation therapy, rheumatoid arthritis, blood poisoning, and food poisoning (1,5,7,9).”

(Numbers in parentheses refer to citations of scientific literature in the WHO monograph.)

Statements of Nutritional Support from Notification Letters to FDA

“For immune system function.”

“Nutritionally supports healthy immune function.”

“Helps stimulate natural resistance.”

“Echinacea has been the subject of numerous scientific studies involving its ability to help maintainnatural resistance.”

“Many Native American tribes have used Echinacea, or purple coneflower, for centuries. TheCheyenne and Comanche gathered this plant for use during cold seasons. It quickly won the favor ofearly European settlers and has now become a well-loved herb both here and abroad. Scientificresearch studies on Echinacea abound, documenting its ability to help maintain overall health andwell-being.”

“Echinacea promotes the body’s natural resistance by supporting a healthy immune system. Echinacea continues to be popular in Europe to strengthen and enhance overall well-being.”

Figure 3



RHIZOMA ZINGIBERIS

WHO Model Monograph

“11.1 Uses supported by clinical data.

The principal clinical use of ginger is for the prophylaxis of nausea and vomiting associated withmotion sickness (20-23), postoperative nausea (24), hyperemesis gravidarum (25), and sea2

sickness (26,27).

11.2 Uses described in pharmacopoeias and in traditional systems of medicine.

Ginger is also indicated for the treatment of dyspepsia, flatulence, colic, vomiting, diarrhea,spasms and other stomach complaints (1,2,4, 9,21). Powdered ginger is further employed in thetreatment of colds and flu, to stimulate the appetite, as a narcotic antagonist (1,2,4,6,11,12,21), andas an anti-inflammatory agent in the treatment of migraine headache, and rheumatic and musculardisorders (9,11,12,28).

11.3 Uses described in folk medicine, not supported by experimental or clinical data.

Other medical uses for ginger include the treatment of cataracts, toothache, longevity, insomnia,baldness and hemorrhoids (9,10,12).

Although ginger appears to be clinically effective in the treatment of hyperemesis2

gravidarum, it is currently not recommended for use in morning sickness during pregnancy(25), see Precautions section 15.5."

(Numbers in parentheses refer to citations of scientific literature in the WHO monograph.)

Statements of Nutritional Support from Notification Letters to FDA

“Stimulates digestion. Ginger is an aromatic bitter herb that stimulates digestion.”

“Ginger is one of the world’s most popular spices, and a well researched herb for a healthy lifestyle. The pungent taste of ginger, prized in international cuisine, has been linked to beneficial compoundswhich warm and soothe the stomach. Ginger has been a favorite of travelers since ancient marinersdiscovered it in the exotic Orient.”

“Ginger root is a soothing and warming herb for the stomach and may help maintain a calm stomachwhile traveling.”

“Eases the discomfort associated with traveling. Ginger is an aromatic bitter herb that eases thediscomfort associated with traveling and stimulates digestion to promote gastrointestinal comfort.”



tioned countries as well as by Canada and to have special health benefits, recentother nations. Twelve of eighteen indus- legislation in The People’s Republic oftrialized countries for which information China bans the marketing of unregisteredwas available have formal mechanisms “health foods” and institutes an inspectionallowing therapeutic claims for botanical process for manufacturers of such productsproducts based on a combination of his- (144).torical and scientific information. In somecountries, clinical evidence is required to The Commission concluded that a compre-support recommended uses. In other coun- hensive evaluation of regulatory systemstries, traditional use is sufficient to provide used in other countries for botanicalthe basis for a limited therapeutic claim, but remedies is needed. Such an evaluationa disclaimer may be required (Table 3). should consider the scope of productsSome countries have established lists of covered, the means of assuring safety andingredients that are permitted or not preventing deception, the effect of suchpermitted and/or lists of permitted claims systems on overall medical care, the issuefor botanical products used for therapeutic of defining appropriate OTC uses ofpurposes. WHO has published guidelines products, and the appropriateness andfor the regulation of traditional medicines, applicability of the different types ofincluding botanical remedies (141), and is disclaimers. finalizing a series of model monographs onspecific botanicals (140). The Commission studied these issues in

Japan, China, and other Asian countries all study is needed a comprehensive evaluationhave long histories of use of botanicals and exceeds the mandate of the Commission. Aother natural products. It should be comprehensive evaluation of the U.S. drugrecognized that products defined in the regulatory system and approaches used inUnited States as dietary supplements other countries to the regulation of drugs,(botanicals, vitamins, minerals, amino acids, alternative medicines, and traditionalhormones, enzymes) are generally regulated botanical remedies is long overdue.as drugs in Japan, China, and other Asiancountries (70,121,133). Direct comparison If the study were to suggest the use ofof the Japanese and Chinese regulatory botanical remedies under a lower standardsystems with that of the United States is of efficacy and a different approval processfurther complicated because of differences than that presently required by law forin nomenclature and classifications. drugs, one member strongly recommends,

In China, traditional Chinese medicine uses the need for a disclaimer that states: “Thismore than 6000 natural products. About product is not generally recognized by500 are most commonly used and of these experts and has not been approved by FDAabout 82 percent are derived from plants,12 percent from animals, and 6 percent areminerals. Most of these are regulated asdrugs (70). With regard to foods purported

detail and concluded that although such a

in such a case, that the review also consider



Table 3

EXAMPLES OF DISCLAIMERS USED IN OTHER COUNTRIES

Country Disclaimer

Belgium “traditionally used in . . ., even though its activity has not been establishedaccording to the actual criteria of evaluation of medicines.”1

Canada “traditional medicines”1

France “traditionally used for . . .” or “used in . . .”1

Germany “Traditionally used (e.g.) for preventive purposes. This product is not intended forthe cure or mitigation of illness, physical deficiencies or ailments. Anyone whohas such illness or ailment should consult a physician. This product is usedtraditionally and it cannot be deduced therefrom whether the product is generallyuseful.”2

Greece Wording frequently used: “possibly effective” and “traditionally used”1

Ireland “The wording on the labeling is mandatory and states the following:i) Do not take in connection with other medications without having consulted

a physician.ii) Do not use for longer than two weeks. The drug safety cannot be

guaranteed for a prolonged period of use.iii) Should the condition not improve, consult a physician.iv) Allergic reactions are possible.v) Traditional herbal remedy for short-term treatment of slight discomforts and

that should . . . not be used for extended periods without the advice of aphysician.” 1

United Kingdom “a traditional remedy for the symptomatic relief of . . .” and “if symptoms persist,consult your doctor”1

Gericke, N. 1995. The regulation and control of traditional herbal medicines: an international overview with1

recommendations for the development of a South African approach. Working draft document. Cape Town, SouthAfrica: Traditional Medicines Programme, University of Cape Town.Nozari, F. 1994. Dietary supplements. Report to Congress. LL94-3. Washington, DC. 2



as effective based on adequate and well- not have participated in the OTC review,controlled studies.” A change in the drug reportedly out of a concern that FDAapproval process or the standards for drug would not consider approving botanicalefficacy would require legislative action. ingredients.

Some witnesses at Commission hearingssuggested that the regulatory system in theUnited States should accommodate thera-peutic claims for products currently mar-keted as dietary supplements. However, asdefined in DSHEA and FDCA, productspromoted for the treatment, prevention,mitigation, or cure of disease fall outside ofthe definition of dietary supplements. Tothe extent that botanical preparations aremarketed for use as dietary supplements,their usage and all aspects of their labelingshould comply with the requirements ofDSHEA.

4. OTC Drug Uses of BotanicalProducts

Public testimony before the Commissionindicated that many of the recognizedtraditional uses of botanical products aresimilar to those classified in the UnitedStates as OTC drug uses. Based on thetestimony presented, the Commissionbelieves that the history of use and thescientific evidence available for somebotanical remedies may be sufficient tojustify OTC approval within the U.S. drugregulatory system as it currently exists.

For the past 25 years, FDA has beenreviewing the safety and efficacy of OTCdrugs. Some botanical ingredients havebeen reviewed. Of these, six were listed assafe and effective for their intended usesand more than 150 were eliminated fromconsideration. However, the Commissionbelieves many botanical manufacturers may

The Commission understands that petitionsfor OTC approval of two botanicalproducts (valerian as a sleep aid and gingeras an antiemetic or for relief of symptomsof motion sickness) were submitted in 1992to FDA by the European-American Phyto-medicines Coalition but have not yet beenapproved.

In light of the increased public interest inbotanical remedies, the Commissionbelieves that FDA needs to give specialattention to the feasibility of approvingbotanical remedies for OTC uses in cases inwhich sufficient evidence is available. TheCommission recommends that FDAconvene a botanical products review panelto review petitions concerning suchproducts. Such a panel should includeexperts with an appropriate scientificbackground in pharmacognosy as well asexperts in other applicable disciplines. Inits deliberations, this panel should givepriority to botanical remedies having thestrongest supporting evidence. Initialcandidates might include, for example, thebotanical products for which the U.S.Pharmacopeial Convention, Inc., iscurrently establishing standards (132)and/or botanicals for which WHO hasprepared draft model monographs (140).

The Commission urges FDA to put a highpriority on expediting such a review panel.FDA should also explore whether it wouldbe helpful to convene a scientific con-ference or workshop on a given product orset of products. The Commission also urges



manufacturers of botanical products to products. For example, in the case ofprepare and submit scientific data as well as certain OTC drugs used for earwaxinformation on the “material time and removal, an FDA advisory panel reviewedextent” of use of the ingredient for the studies and clinical data showing thatrelevant purposes to facilitate review when carbamide peroxide in anhydrous glycerin isFDA requests such data (39). effective in removing earwax. However,

To be approved as OTC drugs, products neither double blinded nor placebo con-trol-must be generally recognized as safe and led (59). FDA subsequently acknowledgedeffective (116). Proof of safety includes that it agreed with the panel’s conclusionsadequate testing by methods reasonably and waived the requirement for double-applicable to show that an OTC drug is safe blinded or placebo-controlled studies. FDAunder the prescribed, recommended, or stated that the methods of investigation,suggested conditions of use. General along with the results of the studies, andrecognition of safety is ordinarily based on human experience justified the waiver.published studies, which may be cor- Further, the study subjects were “examinedroborated by unpublished studies and other professionally” and the earwax removaldata (117). If these standards for safety are product achieved its intended effect bynot met, submission of a new drug applica- means of “mechanical action” (59). FDAtion is required. The U.S. Supreme Court promulgated a final rule based on thehas stated that it “may, of course, be true panel’s conclusions and the agency’sthat in some cases general recognition that concurrence (58).a drug is efficacious may be made” without this kind of testing, but “the reach of Some members of the Commissionscientific inquiry” is the same (139). expressed concern that the existing FDA

Proof of effectiveness requires controlled controlled clinical studies would precludeclinical investigations that meet the approval of some botanical remedies asregulatory criteria for adequate and OTC drugs because these types of studieswell-controlled studies (115), unless the have not been done. However, they alsorequirement is waived because it is not noted that over the past several years, OTCreasonably applicable or essential to the drug review panels and FDA reviewersvalidity of the study and alternative have occasionally applied standards to somemethods of investigation are available products that differ from those specified in(118). Proof of efficacy may also take into the CFR (116).account partially controlled or uncontrolledstudies, clinical studies by qualified experts, For example, in a review of slippery elmand experiential reports; isolated case bark as an antitussive OTC drug, an FDAreports and random experience are not panel in 1976 observed that there was aconsidered. long history of safe use but that there were

FDA has waived requirements for well- (63). It noted that data to support efficacycontrolled clinical studies for some OTC were needed. In 1982, another FDA

the panel noted that these studies were

requirements for adequate and well-

no well-controlled studies of effectiveness



advisory panel, citing the 1976 advisory be equity in the OTC review process andpanel report, recommended that slippery that it would apply equally to currentlyelm bark be approved as a safe and effective approved OTC drugs and to any botanicaloral demulcent (60). The second advisory product covered by a new review.panel reviewed no new data. Based on thefindings of this second panel, FDAproposed that elm bark be recognized as asafe and effective oral demulcent (56).

Similarly, in approving witch hazel as anOTC skin protectant drug, FDA relied onan advisory panel review of data submittedby manufacturers, absence of reports ofadverse effects, and long history of use(61). The advisory panel referenced oneanimal study and one in vitro study of bloodclotting efficiency. FDA’s approval wasbased on the advisory panel’s review andinformation published by the U.S.Pharmacopeial Convention, Inc., as suffi-cient to establish safety and effectiveness(54).

The Commission recommends that theamount of evidence required to support anOTC claim for a botanical product bedetermined specifically for each type of usebeing considered. The type of evidence thatwas required for OTC drugs alreadyapproved for certain uses should be thebenchmark for determining what is gen-erally recognized as sufficient evidence forbotanical products intended for the sameuses now. If a higher standard is deemed tobe required today than was requiredhistorically, justification should be providedby FDA to show that such a higher standardis in the best interest of consumers who arecurrently using OTC drugs approved undera different standard. The Commission’srecommendation regarding creation of anOTC review panel for botanical remedies isbased on the assumption that there would

FINDINGS

The Commission recognizes that DSHEAincludes botanicals under the definition ofdietary supplements and does not intend torecommend any change in legislation toalter the status of these products as dietarysupplements. They should continue to beavailable as dietary supplements whenlabeled as dietary supplements in accord-ance with DSHEA. Manufacturers shouldmake every effort to inform consumers andhealth professionals of the basis for anystatements of nutritional support that aremade in the labeling of these products asdietary supplements.

The Commission observed that manybotanical products are used traditionally forprevention and treatment purposes. Thescientists on the Commission noted that insome cases, current scientific evidencesupports such uses. Most Commissionersconcluded that consumers would be betterserved by clear information regarding suchuses than by the limited statements ofnutritional support permitted by DSHEA. Current efforts to use statements of nutri-tional support to suggest such uses withoutovertly stating them may not providesufficient information to consumers andmay also create a climate of deception thatserves neither the industry nor consumers.The Commission believes its recommenda-tion to encourage manufacturers wishing tomake claims that go beyond those allowedby NLEA or DSHEA to submit them forOTC review would be in the public interest.



Botanicals have always been included aspotential candidates for OTC status. TheCommission is not recommending a newcategory of OTC drugs, but believes that adedicated OTC panel on botanicals wouldfacilitate the review of appropriate OTCclaims. In the judgment of the Commission,the extension of the existing OTC processto botanical remedies that are most likely tomeet the existing requirements would notrequire new legislation but could beaccomplished within the current legal andregulatory framework for OTC drugs. Thisconcept is consistent with the OTC drugguidelines where there is generalrecognition of safety and efficacy andadequate current scientific evidencecomparable to the evidence that wasconsidered in approving similar OTC usesin the past.

In many other industrialized countries,specific claims for botanical remedies andmedicines are permitted, generally in aseparate category of nonprescriptionproducts within the drug regulatory system.Some Commissioners believe there shouldbe a comprehensive evaluation of thepotential applicability of such a system inthe United States.

GUIDANCE

! More study is needed regarding theestablishment of some alternativesystem for regulating botanicalproducts that are used for purposesother than to supplement the diet butthat cannot meet OTC drug require-ments. The study should include thetypes of disclaimers that might applyand the appropriateness of such asystem within the U.S. regulatoryframework. Such a comprehensive

study would go beyond the mandate ofthis Commission, which is limited todietary supplement uses of theseproducts.

! The Commission concluded that acomprehensive evaluation of regula-tory systems used in other countriesfor botanical remedies is needed. Suchan evaluation should consider thescope of products covered, the meansof assuring safety and preventingdeception, the effect of such systemson overall medical care, the definitionof appropriate drug uses of products,and the appropriateness andapplicability of the different types ofdisclaimers.

RECOMMENDATIONS

! The Commission recognizes that,under DSHEA, botanical productsshould continue to be marketed asdietary supplements when properlylabeled.

! The Commission strongly recommendsthat FDA promptly establish a reviewpanel for OTC claims for botanicalproducts that are proposed bymanufacturers for drug uses. Thepanel should have appropriate repre-sentation of experts on such products.



ENDNOTES

1. On September 23, 1997, FDA published a final rule that provides guidelines for the content of notification letters.Specifically, the final rule calls for the notification to contain the following information:

! The name and address of the manufacturer, packer, or distributor of the dietary supplement that bearsthe statement;

! The text of the statement that is being made;! The name of the dietary ingredient or supplement that is the subject of the statement, if not provided in

the text of the statement;! The name of the dietary supplement (including brand name), if not provided . . . in the label where the

statement appears; and! The signature of a responsible individual or the person who can certify the accuracy and completeness

of the information presented and contained in the notification letter and that the notifying firm hassubstantiation that the statement is truthful and not misleading.

2. See Chapter I Endnote.


Chapter IV

ADDITIONAL ISSUES AND RECOMMENDATIONS

IDENTIFIED BY THE COMMISSION

INFORMATION FOR CONSUMERS AND HEALTH PROFESSIONALS

The Commission devoted considerable cancer. Another economic analysis of theattention to the need for assessment of regulation of health claims addresses theconsumer understanding and to the use of credibility of these claims on labels (10).dietary supplement labeling. The information Citing studies by Deighton in 1983 and 1984needs of consumers and health professionals (16,17), these authors assert that consumersmust be met appropriately to ensure that the tend to base their decisions on a “portfolio”purposes of labeling are achieved. of health information rather than on

The principle of using food labels to tend to treat advertising claims withcommunicate messages that encourage a skepticism and check the truthfulness ofhealthful diet and inform consumers of foods claims against neutral sources of informa-that may meet various nutritional objectives tion, such as newspapers, magazines, books,is well established (126). The emphasis has physicians, and government sources.been on ensuring that the message on anygiven food label is of high quality, A recent review on communication of food,understandable, based on sound scientific nutrition, and health messages did notinformation, and consistent with national include dietary supplement labeling specifi-nutrition policy. A review of issues related cally but did address consumer understand-to consumer understanding of conventional ing of nutrient content and health claims onfood label claims is instructive because it is food labels (80). In an appendix to thispotentially analogous to the understanding of report, Levy (83) indicates that consumers indietary supplement label claims. focus groups were interested in having

Ippolito & Mathios (76) provide evidence diet and disease. Some Commissionersthat in the ready-to-eat cereal market, interpret this study as suggesting thatproducer advertising and labeling are a consumer research has not yet establishedsignificant source of information and reach a “mandate” for having health informationconsumers who are not being as well on food labels as opposed to obtaining suchinformed by government and general information from health care providers,information sources. They confirm the ability books, or the print and telecommunicationsof producer advertising and labeling to media. Moreover, considering that foodeffectively communicate the link between labels are viewed by consumers as reflectivediet and health to the public. However, it is of the manufacturer’s interest in selling theimportant to note that the investigators product, consumers are skeptical about theevaluated consumers’ changes in cereal veracity of health messages on food labels. choices during a time (1985 and 1986) when This skepticism may be exacerbated by thecereal manufacturers promoted their prod- prevailing climate in which many consumersucts using fiber-related health claims and have a sense that they are constantly being

that, at that time, there was no significantagreement in the scientific community on therelationship between dietary fiber and

marketing information alone. That is, they

information about the relationship between

Chapter IV Additional Issues and Recommendations Identifiedby the Commission


bombarded with conflicting information health benefits of the products, consumersabout nutrition. In this context, the study generalized positive impressions conveyed(83) may suggest that the precautions taken by a nutrient content or health claim toto make nonmisleading food label claims benefits other than those explicitly identifiedinvolving any aspect of the diet-health in the message (sometimes referred to as arelationship may satisfy policy makers but “halo” effect). However, fewer of them didmay be ineffective in reassuring consumers so in response to open-ended questions (84).that label statements are reliable. In As was also evident in FTC studies (10,76),addition, while nutrient content claims can consumers do not tend to look at labelbe verified by reference to the Nutrition claims or advertising claims in isolation.Facts panel on the label, most other types ofclaims cannot be verified without further In contrast to the situation with food labels,information, which by its very nature is too in which policy makers seemed to be leadingextensive to include on a label. the public, support by consumers and

After several years of deliberations, FDA that consumers want more flexibility in labelapproved a number of health claims for use claims for dietary supplements (136). Thein food labeling and set forth “model health interest of policy makers in meeting thisclaims” to guide manufacturers. Recent consumer need is reflected in DSHEA’sresearch on consumer understanding of food provision for the establishment of thelabel claims suggests that perceptions Commission on Dietary Supplement Labelsformed from label claims may differ from to address “how best to provide truthful,those intended in setting regulatory criteria. scientifically valid, and not misleadingIn focus groups conducted by FDA relating information to consumers.” Among theto health claims on food products, con- findings identified by Congress in DSHEAsumers did not discriminate between health was the concern that “although the Federalclaims and nutrient content claims when government should take swift action againstasked about statements on food packages products that are unsafe or adulterated, thethat described possible health benefits of Federal government should not take anyparticular products (83). This conclusion actions to impose unreasonable regulatorywas confirmed in a subsequent quantitative barriers limiting or slowing the flow of safestudy of consumers’ perceptions when products and accurate information toexposed to food packages with various consumers.” In the view of those whohealth claims and claim formats (84). When promote dietary supplements, the interest inasked which food packages contained any allowing flexibility in making label claims for“health” information, more than 90 percent supplements seems to be more urgent thanof respondents identified products with only for foods. One reason for this is that whilenutrient content claims. Further, at least four foods are consumed for many reasons,times as many respondents described the including health, anticipated health benefitshealth benefits of the product in terms of its are the only reason for consumingnutrient characteristics as in terms of its supplements. Thus, labeling with respect toeffects in alleviating disease. When asked potential health benefits may be moreclosed-ended questions about the possible

industry for passage of DSHEA suggested



important in supplement choice than in food health to consumers on the product label, aschoice. authorized by NLEA and DSHEA. Reports

A syndicated study of 2,010 men and women effort must go into providing information(71) indicated that 58 percent of vitamin that consumers understand. Clear, nonmis-and/or mineral supplement users read the leading communication of dietary supple-supplement label always, almost always, or ment attributes may pose unique challenges.most of the time. Of these, 33 percent The understanding by older adults oflooked for an explanation of benefits to be information relating to dietary supplementsgained from taking supplements and 23 merits particular attention because olderpercent looked for scientific findings adults represent a substantial proportion ofsupporting use of the supplement (e.g., the users of dietary supplements (142).health claims). However, 78 percent ofregular users believed that scientific informa- Consumer comprehension of the uses oftion on package labels was very or dietary supplements may be hampered by asomewhat important. The study indicated lack of attention to dietary supplements bythat scientific information and/or functional the traditional sources of consumer infor-or health claims on product labels are mation about diet and health. Althoughimportant to and wanted by consumers. surveys show that substantial numbers ofHowever, the study pointed out that this Americans consume dietary supplements, theinformation is viewed by consumers in the Commission believes that guidance providedcontext of information from other sources by some scientific, health, and nutritionand their own knowledge and experience. societies on supplement use is often limited.The effective use of scientific information on Evidence suggests that the American publiclabels may require a certain amount of obtains more information about diet andeducation and personal experience on the health from the media than from physicianspart of the consumer (71). and dietitians (85,127). Also, nutritional

FINDINGS

The Commission recognizes that evaluationof consumer information needs relating todietary supplements is an important issueand makes several recommendationsintended to provide more useful label infor-mation to consumers. Recent studies ofconsumer perceptions of food label claimsillustrate the potential for miscommunicationdespite the efforts of policy makers toestablish clear labeling guidelines and ofmanufacturers to comply with them. TheCommission believes that there is value inproviding information about nutrition and

on consumer research indicate that adequate

guidance by the Federal governmentprovides limited discussion of supplementsthat may help consumers make appropriatedecisions about supplement use (135).Current policy statements say thatconventional foods should provide needednutrients and that supplements are largelyunnecessary in the context of a well-chosendiet.

The Commission believes that some profes-sionals in medicine and nutrition devotemore effort to refuting unsubstantiated andunrealistic claims than to providing soundinformation on appropriate, scientificallyvalid uses of dietary supplements. Research



is needed on the attitudes of health and ing information to consumers so that suchnutrition professionals toward supplements consumers may make informed andand the extent to which these attitudes are appropriate health care choices for them-sufficiently specific (i.e., differentiating selves and their families.” Thus, theamong different types and uses of dietary Commission concludes that the dietarysupplements) and informed. Such research supplement industry has a responsibility notmay reveal ways in which health and only to affirm that such evidence exists, butnutrition professionals can better help the also to make summaries of informationpublic interpret label information and about the scientific evidence for statementsscientific literature on dietary supplements. of nutritional support and product safetyHealth professionals need to take into available to the public. The Commission isaccount scientific developments that demon- suggesting that these summaries includestrate the benefits of dietary supplements. evaluation of evidence from observationalThere now are scientific studies and and experimental scientific studies on thesignificant scientific agreement to support effects of the specific dietary supplement orhealth claims on some dietary supplements. its active ingredient(s), if known.Dietary supplements are also permittedunder DSHEA to make statements of Further, the dietary supplement industrynutritional support when the claims are should be responsive to requests for suchsubstantiated and not misleading. To enable summaries of evidence by interested parties.health professionals to evaluate these uses of These summaries could be provided bydietary supplements, and to advise con- manufacturers or independent organizations.sumers about the uses, the health profes- A publicly accessible database might be asionals need to have access to adequate more efficient means of communication.information about the scientific basis for the Summaries or the database could be devel-statements. oped and maintained by a government

In Section E of Chapter III of this report, the consumer organization, or a partnership ofCommission suggests that manufacturers such organizations. Criteria for inclusion ofaffirm in the notification letter, or in a data should be stated in each summary.separate public notice, that they have evi- Data summaries on specific dietary supple-dence to document statements of nutritional ments themselves, or a database, would helpsupport and that the product is safe for its consumers, health professionals, and healthintended use. The Commission also con- care organizations in evaluating the extent ofcludes that some synopsis of the scientific scientific evidence that supports labelevidence regarding statements of nutritional statements. In addition, publicly availablesupport and product safety should be data summaries on specific dietary supple-available to potential buyers of dietary ments or a publicly accessible database ofsupplements. This conclusion is based these would have considerable educationalprimarily on the mandate in DSHEA which value to all users.indicates that a major role of the Commis-sion is to “evaluate how best to provide For example, it would be important fortruthful, scientifically valid, and not mislead- consumers and health professionals to know

agency such as ODS, a trade association, a



whether a statement of nutritional support be made on the basis of adequate experience.for a dietary supplement relating to a If the summaries are classified as labeling,structure or function of the body is based on they should bear the same disclaimerclinical data or on a long history of use of required by DSHEA for statements ofthe supplement for the purpose mentioned in nutritional support.the statement of nutritional support. Similar-ly, it would also be important to know As indicated previously, Congress made itwhether a statement relating to a biochemi- clear, in passing DSHEA, that these prod-cal mechanism is based primarily on in vitro ucts and information about these productsstudies of the physiological function of should be available so that consumers couldactive compounds in the supplement or make “informed and appropriate health carewhether observational or experimental ani- choices for themselves and their families.”mal and human data are available to support The Commission believes that providingthe reputed effects. consumers and health professionals with

The Commission recognizes that the sum- scientifically valid evidence regardingmaries would need to be prepared with care substantiation of statements of nutritionalin order to provide consumers and health support and product safety for specificprofessionals with responsible information.Summaries should be balanced and notmisleading. Because statements of nutritionalsupport cannot, under the provisions ofDSHEA, claim to prevent or treat a diseaseor disorder, the summaries should similarlynot make these types of claims.

The Commission believes that consumersand health professionals should have fullaccess to the information supportingstatements of nutritional support. The sum-maries should also indicate how healthprofessionals can obtain access to the studiesand evidence that support the statements.Full access would facilitate the ability ofhealth professionals and consumers toevaluate these statements.

There may be a need to clarify whether thesesummaries are labeling or are publicationsexempt from classification as labeling.Currently, experience with such publicationsis quite limited, and any legislative orregulatory determination of this sort should

appropriate and nonmisleading summaries of

dietary supplements would support this goal.

GUIDANCE

! The Commission urges that dietarysupplement labeling be evaluated inadditional consumer research to deter-mine whether consumers actually wantand can utilize the information providedby existing FDA regulations, by therequirements of DSHEA, and in therecommendations of this Commission.The Commission recognizes that con-sumer understanding of statements ofnutritional support and health claims, aswell as consumer perception of dietarysupplement use based on literature atthe point of sale, are important aspectsof the use of information that requireadditional and continued assessment.

! The Commission believes that it isimportant for health and nutrition profes-sionals to become more knowledgeableabout all types of dietary supplementsand to assist the consumer in makingappropriate health care choices withrespect to use of dietary supplements.



! The Commission urges manufacturersto make available publicly balanced andnonmisleading summaries of the evi-dence substantiating statements ofnutritional support and product safety forthe intended use at the stated dosage.The summary should not claim use forprevention or treatment of disease. support, NLEA health claims, and OTC drug

NEED FOR INDUSTRY EXPERTADVICE ON SAFETY, LABELSTATEMENTS, AND CLAIMS

The Commission believes the industry shouldbe more proactive in incorporating scientificinput to its decision-making regarding thesafety and benefits of dietary supplements.The establishment of one or more expertadvisory committees could be a productiveway of obtaining such scientific input for theindustry. Such committees might serve in anadvisory role to individual companies, tomembers of specific trade associations, or tothe industry as a whole, depending on thenature of the support available and themechanism used for establishing suchcommittees. Public comments received onthe Commission’s draft report expressedconcern that these advisory committeesmight take over the role of reviewing NLEAhealth claims, but that was not theCommission’s intent. The outside expertreview that the Commission urges FDA toseek when evaluating health claims is anentirely separate topic from the industry’sinternal need for more scientific guidance,and the two topics are treated separately inthis report. This section of the reportaddresses the need for industry to developone or more mechanisms for strengtheningits scientific basis for making labelstatements.

Dietary supplements are eligible for a varietyof label statements and claims, each of whichis subject to unique regulatory requirements.Despite differing regulatory provisions, in apractical sense, messages conveyed toconsumers by label statements of nutritional

claims are often similar. Manufacturers ofdietary supplements have several options indetermining which type of statement or claimis appropriate for a given product, inevaluating the degree of substantiationrequired for the statement or claim, and indeciding whether the evidence is sufficient tosubstantiate a statement of nutritionalsupport under DSHEA or to justify apetition to FDA for approval of an NLEAhealth claim or an OTC drug claim.

The Commission believes the dietarysupplement industry and consumers alikewould benefit from an increased level ofscientific input into decisions regarding labelstatements for dietary supplements. Inaddition, as emphasized elsewhere in thisreport, the Commission considers it axio-matic that dietary supplements must be safefor their intended uses, and scientific input isessential in making such determinations.Accordingly, the Commission recommendsthat the industry consider establishing anexpert advisory committee on dietarysupplements to provide scientific review oflabel statements and claims and to provideguidance to the industry regarding the safety,benefit, and appropriate labeling of specificproducts. Such a committee might besupported by one or more industry tradeassociations or might be established as anindependent entity funded by extramuralgrants and/or fees for services.



A number of models illustrate the value and participation by the U.S. Pharmacopeialreliability of expert outside review as a Convention, Inc., FDA, the Nationalmeans of helping to resolve issues relating to Academy of Sciences, and internationalthe safety and/or benefits of specific bodies such as WHO. Regardless of theproducts or groups of products. The Flavor composition of the committee, proceduresand Extract Manufacturers Association should be in place to avoid conflict of(FEMA) has conducted its own GRAS interest.review of flavor compounds and the Cos-metic, Toiletry and Fragrance Association, The Commission recognizes that the supportInc. (CTFA) has conducted its own Cos- of an expert advisory committee in themetic Ingredient Review. In these two pursuit of a comprehensive review of dietaryinstances, the reviews are organized and supplement ingredients would be a majorfunded by industry but involve extramural and costly undertaking. However, thescientists with appropriate expertise and success of the CTFA and FEMA reviewsexperience who conduct quality reviews that indicates that the value of the undertakingare made available publicly. might be well worth the investment.

AHPA proposed a botanical ingredientreview to FDA as an alternative mechanismfor approving NLEA health claims forbotanical ingredients. Although the agencydeclined to incorporate such an outsidereview into its procedures for approvinghealth claims, the Commission believes therewould be value in the industry’s undertakingsuch reviews in the spirit of self-regulationand with the goal of increasing consumerconfidence in both the safety and the efficacyof dietary supplements. SomeCommissioners believe that an expertoutside review would also enhance thequality of petitions submitted to FDA forapproval of an NLEA health claim or anOTC drug claim for a product.

To assure the credibility of an expertadvisory committee, any such committeeshould be composed of scientific expertswith appropriate specialties in nutrition,pharmacognosy, pharmacology, healthpromotion and disease prevention, medicine,and toxicology. Some Commissionersbelieve it would be desirable to include

GUIDANCE

! The Commission recommends that thedietary supplement industry considerestablishing an expert advisory commit-tee on dietary supplements to providescientific review of label statements andclaims and to provide guidance to theindustry regarding the safety, benefit,and appropriate labeling of specificproducts. Such a committee might besupported by one or more industry tradeassociations or might be established asan independent entity funded byextramural grants and/or fees forservices.

RESEARCH ISSUES

DSHEA recognizes the importance ofresearch in relation to dietary supplements.In the findings section of the legislation,Congress indicated that the importance ofnutrition and the benefits of dietarysupplements to health promotion and diseaseprevention have been increasinglydocumented in scientific studies. TheCommission endorses the continuation ofthese types of studies. DSHEA establishes



ODS within NIH to promote scientific According to data provided from the Humanstudies of the benefits of dietary supplements Nutrition Research and Information Man-in maintaining health and preventing chronic agement System (HNRIMS), in fiscal yeardisease and other health-related conditions. 1995, expenditures by Federal agencies onThus, it seems clear that Congress human nutrition, research, manpower devel-recognized that use of dietary supplements opment training, and education totaled aboutshould be based on a strong foundation of $540 million (82) (Table 4). Comparison ofscientific research. data from 1986 to 1995 (Table 5) suggests

As discussed elsewhere in this report, the nutrition research and training (74,82).Commission considered the availability of However, the portion of research directlyscientific evidence supporting the benefits of applicable to dietary supplements cannot bedietary supplements and deliberated on the determined. ODS is defining a series oftype of evidence that may be used to codes for dietary supplements to allowsubstantiate health claims and statements of inclusion of data on dietary supplementnutritional support. In the course of these research expenditures in the HNRIMSdeliberations, it became evident that the databases. This effort will be completed laterresearch base for supporting various types of this year or in 1998. statements for dietary supplements is highlyvariable. There has been relatively little Federal

Over the past several decades, the Federal mechanism of action of botanical products.government has supported a significant body In view of the public’s interest in dietaryof basic research on ingredients used in supplements, the Commission believes thatdietary supplements, specifically vitamins, additional Federal funding should be directedminerals, and amino acids. In addition to the toward evaluation of the potential healthbasic work on most of the vitamins and benefits and safety of a wide range of dietaryminerals, in recent years large clinical or supplements, including botanical products.epidemiologic studies have been carried out Such research results can providedealing with the relationship between information that consumers can use to makenutrients and diseases (e.g., vitamins E and informed decisions about their health. C and cardiovascular disease and cancer,selenium and cancer, tene and cancer,calcium supplements and osteoporosis).

The Commission is unable to ascertain withcertainty the magnitude of federally sup-ported basic and applied research associatedwith dietary supplements due to difficultiesin retrieving such data. However, someestimates can be derived from existinginformation.

a progressive increase in Federal funding for

support of basic research dealing with the

Table 4

FISCAL YEAR 1995 EXPENDITURES AND NUMBER OF PROJECTS IN HUMAN NUTRITIONRESEARCH, MANPOWER DEVELOPMENT, TRAINING, AND EDUCATION

BY FEDERAL AGENCIES

Percent ofTotal Projects

Number ofProjects

Percent of TotalExpenditures

Expenditures(Dollars

in Thousands)

Department of Health and Human Services (DHHS):

National Institutes of Health

Food and Drug Administration

Centers for Disease Control

Health Resources and Services Administration

Total DHHS

Agency for International Development

National Science Foundation

Department of Veterans Affairs

Department of Commerce

Department of Defense

National Aeronautics and Space Administration

U.S. Department of Agriculture

Total Federal Expenditures

428,687

1,464

4,713

344

435,208

6,104

41

9,962

502

3,545

855

84,217

540,436

79

<1

1

<1

81

1

<1

2

<1

<1

<1

16

100

2,620

15

3

2

2,640

14

8

558

1

6

8

1,137

4,372

60

<1

<1

<1

60

<1

<1

13

<1

<1

<1

26

100

a Estimateb Totals may be imprecise due to rounding

Agency

b

a

Source: This table was modified from information provided by the Human Nutrition Research and Information Management System (82).

Chapter IV

Additional Issues and R

ecomm

endations Identifiedby the C

omm

ission

Co

mm

ission

on

Die

tary S

up

ple

me

nt L

ab

els

67

a In FY/89, CDC includes NCHS.b In FY/93, NIH includes ADAMHA.

Source: This table was modified from information provided by the Human Nutrition Research and Information Management System 13th Progress Report (74, 82).

Table 5

OBLIGATIONS FOR NUTRITION RESEARCH AND TRAINING BYAGENCY, FISCAL YEARS 1986 THROUGH 1995

(THOUSANDS OF DOLLARS)

Department of Health and Human Services (DHHS):


Food and Drug Administration

Alcohol, Drug Abuse, and Mental HealthAdministration (ADAMHA)

Centers for Disease Control (CDC)

National Center for Health Statistics (NCHS)

Health Resources and Services Administration

Total DHHS

U.S. Department of Agriculture

Agency for International Development

National Science Foundation

Department of Veterans Affairs

Department of Commerce

Department of Defense

National Aeronautics and Space Administration

Total Federal Expenditures

Agency

212,978

8,143

7,548

569

804

1,151

231,193

61,265

4,998

�

5,500

1,000

782

�

304,738

1986

260,611

6,799

7,685

561

3,885

1,147

280,687

67,601

4,364

�

2,021

946

533

�

356,152

1987

276,195

10,470

7,545

537

4,227

1,625

300,599

70,029

6,037

�

2,816

1,078

4,091

37

384,687

1988

286,975

10,063

9,603

5,216

�

1,114

312,971

65,433

6,492

�

3,104

989

421

�

389,410

1989

292,359

7,397

11,876

5,084

�

959

317,675

62,467

4,147

�

2,379

1,016

488

�

388,172

1990

310,810

10,527

18,875

6,006

�

1,717

347,935

63,756

4,617

79

2,139

937

849

428

420,739

1991

343,788

10,958

15,019

6,074

�

1,858

377,698

70,563

4,157

19

2,366

1,199

3,631

679

460,311

1992

373,251

7,661

�

5,579

�

1,025

387,515

67,435

3,958

29

4,379

981

3,176

681

468,153

1993

400,701

2,054

�

5,633

�

579

408,966

73,912

3,922

29

4,076

576

2,869

687

495,038

1994a b

428,687

1,464

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4,713

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344

435,208

84,217

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3,545

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1995

Chapter IV

Additional Issues and R

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Support for research from the private sector may be difficult for such companies todepends to a considerable degree on the envision increased economic return oneconomic return that may be expected from greater research investment. In lieu ofinvestments in research. While some investment in research, substantiation ofcompanies make grants and donate products statements of nutritional support hasfor research studies, the Commission was been based on extension of publiclyunable to obtain any reliable information on available research, research conductedthe dietary supplement industry’s overall overseas, or a history of use.investment in research on product efficacyand safety. Public testimony to the Commis- ! The Commission heard testimony in itssion indicated that many of the products public hearings that most dietarymarketed as dietary supplements do not have supplements, being natural or genericpatent protection, thus marketing advantages products, cannot be given effectiveobtained through research are difficult to patent protection. Therefore a manu-maintain because the research results would facturer lacks incentive to expendbe available to competitors as well as the resources for research that might benefitcompany supporting the research. The competitors as well as itself. Commission took note of the discussion ofresearch issues related to health claims in the ! Conducting clinical research to assessrecent Keystone report (80) and believed the validity of statements of nutritionalthat the discussion was particularly relevant support could be difficult. A statementto consideration of mechanisms for support that a product provides a feeling of well-of research on dietary supplements. being may be confounded with the

FINDINGS

The Commission reached the followingconclusions about research issues related todietary supplements:

! The dietary supplement industry isdiverse, with a number of large com-panies and several hundred relativelysmall companies manufacturing and/ormarketing dietary supplements. Thesmall size of many companies con-tributes to limited investment byindividual companies in research onproduct efficacy. These companies havebeen able to market products either withno label claims or now, under DSHEA,with statements of nutritional supportwithout heavy research investment. It

placebo effect, thus double-blind studiesusing placebo would be essential toassessing such statements. A statementthat a product enhances immune functionrequires an appropriate challenge usingacceptable clinical and biochemicalmethodology to determine whether theproduct actually improves resistance tocommon conditions such as colds andflu. Such research is resource intensive.

! Many dietary supplements claim toimprove or optimize the functioning ofthe human body and do not result inimmediate drug-like effects. The “soft”end points of research supporting suchclaims can make clinical research resultsambiguous. The cost of research toprove moderate benefits is significantlyhigher than that of research to prove



immediate relief of disease symptoms.In addition, identification of benefits forparticular segments of the populationwill require either multiple trialsinvolving each group or large studiesthat involve several populationsubgroups.

! For a health claim to be made underNLEA, a considerable body of researchmust demonstrate that a food or dietarysupplement ingredient will reduce riskfor a specific disease or condition. Theresearch base must be sufficient to disclaimer mandated by DSHEA couldpermit significant scientific agreementamong qualified scientists. Existinghealth claims generally have not beenbased on research supported by a singlecompany, but have relied on researchfunded by both government and industry.For example, the recently approvedhealth claim that soluble fiber fromwhole oats reduces the risk of coronaryheart disease was based on researchsupported by NIH and the petitionerover a period of many years.

! Determination of prevention in thegeneral population, or even in apopulation at risk for developing aspecific disease, is more expensive anddifficult than determination of an effectin a population with a disease. Deter-mining any relationship between dietaryingredients and disease or risk ofdeveloping a disease may require numer-ous expensive, large-scale clinical trials.

GUIDANCE

! The Commission believes that the publicinterest would be served by moreresearch that assesses the relationshipsbetween dietary supplements andmaintenance of health and/or preventionof disease.

! Incentive mechanisms should bedeveloped to encourage the dietarysupplement industry to invest inresearch on products offered to theconsumer. FDA might consider amechanism for review of researchconducted to validate a statement ofnutritional support so that the label

be modified or removed. Moreconsideration is needed of ways toprovide sufficient resources to FDA tomake it possible for the agency to takeon such an additional responsibility.

! The Commission recommends that

Federal agencies continue to supportresearch on the health benefits andsafety of dietary supplements. Researchshould be expanded beyond thetraditionally supported areas associatedwith vitamin and mineral supplementsand include research on some of themore promising botanical products usedas dietary supplements.

NIH OFFICE OF DIETARYSUPPLEMENTS

DSHEA established the Office of DietarySupplements within NIH for the purpose ofexploring the potential role of dietarysupplements as a significant part of the



efforts of the United States to improve industry, the scientific community, andhealth care, and to promote scientific study others. The final plan will probably not beof the benefits of dietary supplements in available until after the Commissionmaintaining health and preventing chronic completes this report. Nevertheless, thedisease. Commission believes that critical evaluation

Most of the duties outlined by DSHEA for be essential if the intent of DSHEA is to beODS are related to conducting, coordinat- realized fully.ing, or compiling the results of scientificresearch. ODS is directed by the Act to ODS has great potential, but has so far beenconduct and coordinate scientific research unable to reach that potential due torelating to dietary supplements within NIH, inadequate staffing and funding. If adequateto coordinate funding for such research, to resources can be provided, the Commissioncollect and compile the results of scientific believes ODS could play a valuable role inresearch on dietary supplements, and to providing consumers with information aboutcompile a database of such research. In dietary supplements. In this report, theaddition, DSHEA directs ODS to “…serve Commission is urging manufacturers toas the principal advisor to the Secretary and provide consumers and health professionalsto the Assistant Secretary for Health and with more information regarding theprovide advice to the Director of the substantiation for statements of nutritionalNational Institutes of Health, the Director of support and regarding the safety of products.the Centers for Disease Control and ODS could serve as a depository for thatPrevention, and the Commissioner of Food information, which could be compiled into aand Drugs on issues…” relating to safety, useful database.benefits, and labeling of dietary supplements.

The Commission observes that ODS has sofar not been provided with sufficient staffingor funds to achieve these goals. While anannual budget of $5 million was authorizedby DSHEA in 1994, the Commission notesthat currently, ODS has an annual budget ofabout $1 million. Much of its work overrecent months has focused on assessment ofpriorities among several mandated tasks;collection and organization of informationconcerning research activities, both withinNIH and throughout other Federal agencies;and gathering information on research needs.

The development of a strategic plan has beena major activity of ODS. A draft plan hasbeen developed with the assistance of

of the ODS strategic plan for research will

FINDINGS

The Commission recognizes a need for ODSto be more proactive in fulfilling its pur-poses, including promotion of scientificstudies on potential roles of dietarysupplements in health promotion and diseaseprevention. Appropriations as authorized byDSHEA are essential if ODS is to meet thesemandates of the Act.



RECOMMENDATIONS

! ODS should strive to be an effectivefocal point for research on and under-standing of the health effects of dietarysupplements.

! ODS should place greater emphasis onits assigned role of advising othergovernment agencies on a broad rangeof issues relating to dietary supple-ments.

! Congress should fund ODS at the levelauthorized by DSHEA.


Chapter V

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140. World Health Organization. 1996. World Health Organization draft monographs onbotanicals. Geneva, Switzerland.

141. World Health Organization. 1991. Guidelines for the assessment of herbal remedies.Document prepared at the World Health Organization Consultation in Munich, Germany.June 19-21. Geneva, Switzerland.

142. Wright, J. 1997. Letter containing tables of estimates with the prevalence of use of dietarysupplements from NHANES III, 1988-94. Letter sent to K.D. Fisher. April 30.

143. Wright, P.B. 1997. Director, Pharmacology and Toxicology. Nonprescription DrugManufacturers Association. Written testimony submitted to the Commission on DietarySupplement Labels. March 4. Baltimore, MD.

144. Xinhua News Agency. 1996. Crackdown on poor health food planned next year. ItemNumber: 1224031. December 24. Beijing.

Appendix A

DIETARY SUPPLEMENT HEALTH AND EDUCATION ACT OF 1994

Appendix A is not available in this document.To view this article, please see:http://thomas.loc.gov/cgi-bin/query/z?c103:S.784:

Appendix B

CHARTER OF THE COMMISSION ON DIETARY SUPPLEMENT LABELS

Commission on Dietary Supplement Labels B-1

CHARTERCOMMISSION ON DIETARY SUPPLEMENT LABELS

PURPOSE

The Secretary of Health and Human Services, in order to meet the intent of The DietarySupplement Health and Education Act of 1994, P.L. 103-417, Section 12, is establishing aCommission on Dietary Supplement Labels that will develop recommendations for theregulation of label claims and statements for dietary supplements. The Commission is toevaluate how best to provide truthful, scientifically valid, and not misleading information toconsumers so that such consumers may make appropriate health care choices for themselvesand their families.

The Commission on Dietary Supplement Labels is established for the single, time-limited taskof conducting a study on the regulation of label claims and statements for dietary supplementsand providing a final report to the Secretary of the Department of Health and Human Services(HHS), the President, and the Congress on its findings and possible recommendations.

AUTHORITY

42 U.S. Code 217a, Section 222 of the Public Health Service Act, as amended. TheCommission is governed by the provision of Public Law 92-463, as amended (5 U.S.C.,Appendix 2), which sets forth standards for the formation and use of advisory committees.

FUNCTION

The Commission on Dietary Supplement Labels shall conduct a study on, and providerecommendations for, the regulation of label claims and statements for dietary supplements,including the use of literature in connection with the sale of dietary supplements andprocedures for the evaluation of such claims. In making such recommendations, theCommission shall evaluate how best to provide truthful, scientifically valid, and not misleadinginformation to consumers so that such consumers may make informed and appropriate healthcare choices for themselves and their families.

The Commission may hold hearings, sit and act at such times and plows, take such testimony,and receive such evidence as the Commission considers advisable to carry out the purposes ofthis section. The Commission may secure directly from any Federal department or agencysuch information as the Commission considers necessary to carry out its charge.

B-2 Commission on Dietary Supplement Labels

STRUCTURE

The Commission shall consist of seven members, including the chairperson, appointed by thePresident. Members shall possess expertise and experience in dietary supplements and in themanufacture, regulation, distribution, and use of such supplements. At least three of themembers shall be qualified by scientific training and experience to evaluate the benefits tohealth of the use of dietary supplements and one of such three members shall have experiencein pharmacognosy, medical botany, traditional herbal medicine, or other related fields.

MEETINGS

Meetings shall be held at the call of the Chair with the advance approval of a Governmentofficial, who shall also approve the agenda. It is anticipated that the Commission will meet six(6) to eight (8) times. A Government official shall be present at all meetings.

Meetings shall be open to the public except as determined otherwise by the Secretary; and,records of the proceedings kept as required by applicable laws and Departmental regulations.Notice of all meetings shall be given to the public.

COMPENSATION

Members shall not receive compensation for their service but shall be paid travel and per diemexpenses in accordance with Standard Government Travel Regulations.

ANNUAL COST ESTIMATE

The estimated annual cost of operating the Commission, including travel and per diemexpenses for members, but excluding staff support, is $277,243. The estimated annual personyears of staff support required is 2.5 at an estimated annual cost of $138,535.

REPORTS

The Commission shall prepare a final report to the Secretary of HHS, the President, theSpeaker of the House of Representatives, and the President of the Senate that includes theresults of its study and any findings or recommendations the Commission may choose tomake, including recommendations for legislation.

In the event a portion of a meeting is closed to the public, a report shall be prepared whichshall contain, as a minimum, a list of the members and their business addresses, theCommissions functions, dates and places of meetings, and a summary of the Commissionactivities and recommendations made during the fiscal year. A copy of the report shall beprovided to the Department Committee Management Officer.

Commission on Dietary Supplement Labels B-3

TERMINATION DATE

Unless renewed by appropriate action prior to its expiration, the Commission on DietarySupplement Labels will terminate after delivery of its final report to the Secretary, thePresident, and the Congress, or two years from the date this charter is approved, whichever issooner.

APPROVED:

Appendix C

COMMISSION PROCEDURES

Commission on Dietary Supplement Labels C-1

COMMISSION PROCEDURES

The Dietary Supplement Health and Education Act (DSHEA), signed into law on October 25,1994, mandated the establishment of the Commission on Dietary Supplement Labels. Theappointments of the seven members of the Commission were confirmed by the President onNovember 9, 1995. The Commission received its charter from the Secretary of Health and HumanServices on February 13, 1996.

From February 1996, to August 1997, the Commission held nine meetings. The first fourmeetings focused on obtaining comments, data, and information from interested individuals andorganizations. In addition, the Commission invited testimony from the Food and DrugAdministration (FDA), the Federal Trade Commission (FTC), and several organizations thatrepresent consumer groups as well as the dietary supplement and food industries. Based in parton the testimony received during the course of the eight meetings, the Commission continuallyrevised its list of key issues. Each of these key issues was assigned to an ad hoc subcommitteeof the Commission or to the Commission staff for further research and study, and fordevelopment of draft materials for discussion by the full Commission at subsequent meetings.

Meeting # 1. February 16, 1996, Washington, D.C. The Commission agreed on proceduralaspects and the scope of work. Testimony was received from the Food and Drug Administration,the Office of Dietary Supplements of the National Institutes of Health, and three interestedorganizations. The former two discussed their responsibilities under DSHEA; the latter threeprovided their perspectives on the scope and responsibilities of the Commission.

Meeting # 2. March 8, 1996, Salt Lake City, Utah. Nineteen individuals, representingconsumers, manufacturers, retailers, and dietary supplement industry organizations, addressed theCommission, commenting on the Commission’s charge and discussing issues they thought shouldbe considered by the Commission.

Meeting # 3. April 26, 1996, San Francisco, California. Sixteen individuals and organizationsprovided comments to the Commission. Four represented dietary supplement producers, threepresenters had specific information and comments on herbs and phytomedicines, three othersoffered comments and information from the perspective of educational institutions, five presentedviews of consumers, and one provided a view as a registered dietitian. Two ad hocSubcommittees discussed key issues for Commission consideration and reviewed health claimregulations; both ad hoc Subcommittees reported to the full Commission. The Commission agreedthat the meeting on June 6, 1996, in Orlando, Florida would complete the oral testimonycomponent of the Commission’s efforts and June 30, 1996 would be the cutoff date forsubmission of public comments.

Meeting # 4. June 6, 1996, Orlando, Florida. Thirteen persons, representing scientific societies,consumer organizations, State government officials, and supplement manufacturers, presentedinformation and views to the Commission. Ad hoc Subcommittee reported to Commission oncurrent regulations governing label statements. Commission agreed to extend the deadline forpublic input of written submissions to August 30, 1996.

C-2 Commission on Dietary Supplement Labels

Meeting # 5. September 19 and 20, 1996, Reston, Virginia. Written comments submitted to theCommission as of the extended deadline date, August 30, 1996, were summarized; a number ofrecurrent themes were noted. These included safety issues; effects of label statements;truthfulness of label statements; consumer information; content, and review of, and access to thesubstantiation files supporting product label statements; possible use of external third-partyreview panels; regulatory categorizations of botanical products; and clarification of whatconstitutes a structure/function type of statement of nutritional support. Commission discussionsfocused on the process, procedures, and guidelines for review of label claims and petitions formarketing herbals and botanicals. A representative from the Division of Over-The-Counter DrugProducts, FDA, answered questions concerning the possible application of the over-the-counterdrug review process to botanical dietary supplements that make preventive or treatment claims.A representative from the Division of Advertising Practices, FTC, provided an overview of theagency’s regulatory procedures for dealing with dietary supplements and foods. Summaries ofthe progress of several ad hoc subcommittees held since June 7, 1996, were reviewed by the fullCommission.

Meeting # 6. October 24 and 25, 1996, Washington, D.C. The Commission reviewed andreached tentative agreement on findings and recommendations about several key issues: safetyof dietary supplements, literature at point of sale, content of notification letters, and regulatorymanagement of dietary supplements in other countries. In addition, the Commission discussedregulatory options for herbals and botanicals and explored issues relating to structure/functionstatements and health claims raised by the content of notification letters.

Meeting # 7. December 16, 1996, Washington, D.C. The Commission met to review draftmaterials on events that led to passage of DSHEA and characteristics of consumer use of dietarysupplements. Drafts of tentative findings and possible recommendations for the Commission’sreport were reviewed. The Commission decided to revise these findings and recommendationsand have the redrafts recirculated to the full Commission prior to the meeting on March 4, 1997.The Commission approved the establishment of an Information Response Center to handleinquiries form the public. The Commission discussed the possibility of making a draft of the reportavailable for public comment.

Meeting # 8. March 4, 1997, Baltimore, Maryland. The Commission invited testimony fromspecific groups that had testified previously on the regulatory management of botanical remediesand possible use of third-party evaluation of dietary supplement label statements. Five presentersrepresented various trade organizations in the dietary supplement and food industries, tworepresented public interest groups, and two represented scientific and professional groups. Inaddition, the Commission discussed revised drafts of sections of the report. Comments on reviseddrafts of the findings and recommendations were forwarded to the Executive staff for inclusionin the draft report of the Commission. The Commission agreed to make the draft report availablefor public comments.

Revisions of the several sections of the draft report prepared by individual Commission membersand the staff were circulated to the full Commission from March 5 to May 23, 1997. With theagreement of the Commission members, the publicly available draft report was prepared and

Commission on Dietary Supplement Labels C-3

released for public comment. Submission of written comments from all interested parties wassolicited.

Draft Report Release. Consistent with the decision of the Commission on March 8th, the draftreport was released on June 24, 1997. There is no requirement for release of a draft report ineither DSHEA or the Federal Advisory Committee Act. However, the Commission was awareof the public interest in its work and desired to have an additional period for public comment onthe Commission’s findings and recommendations. Because the Commission’s funding was aboutto expire at the end of Fiscal Year 1997, only a limited time was available for comments.

Meeting # 9. August 14 and 15, 1997, Reston, Virginia. The Commission reviewed over 400comments submitted by the public on the draft report. In addition, the Commission identifiedportions of the draft report that needed further clarification and explanation. The Chair assignedresponsibilities for revisions to the Commission members and staff. A revised final draft wasprepared and circulated to the Commission members for review and approval.

Final Report Release. The final report of the Commission on Dietary Supplement Labels wasdelivered to the Office of the President, the Congress, and the Secretary of the Department ofHealth and Human Services on November 24, 1997. The final report is available from theGovernment Printing Office and is on the Internet at http:\\web.health.gov\dietsupp.

Appendix D

INDIVIDUALS AND ORGANIZATIONS PRESENTING

ORAL TESTIMONY TO THE COMMISSION

Commission on Dietary Supplement Labels D-1

INDIVIDUALS AND ORGANIZATIONS PRESENTING

ORAL TESTIMONY TO THE COMMISSION

Meeting #1, Washington, DC, February 16, 1996

Cordaro, John; Council for Responsible NutritionHoward, Rae; National Nutritional Foods AssociationMarriott, Bernadette M.; Office of Dietary Supplements, National Institutes of Health Rosenberg, Kenneth M.; Pharmavite CorporationScarborough, F. Edward; Center for Food Safety and Applied Nutrition, Food and Drug AdministrationYetley, Elizabeth A.; Center for Food Safety and Applied Nutrition, Food and Drug Administration

Meeting #2, Salt Lake City, UT, March 8, 1996

Anderson, Corey; Trace Minerals ResearchBarney, Paul; Spine Institute of UtahBerg, Dallas; ConsumerBlumenthal, Mark; American Botanical CouncilBowen, Melanie H.; Office of Senator Orrin G. Hatch Farris, Jim; New Frontiers MarketForsberg, Scott; Nature’s Way ProductsHilton, Matthew; Consumer Hinrichs, Jeff; Nutraceutical CorporationHoward, Kenneth M.; Good Earth Natural Foods Israelsen, Loren D.; Utah Natural Products AllianceMartin, Greg; Shaperite Concepts Ltd.Murdock, Ken; National Nutritional Foods AssociationOchsenbein, Steve; ConsumerProchnow, James R.; Patton BoggsRichards, Robert L.; Kaire International, Inc.Scott, Michael; Academy of Clinical Environmental Research & Informational SciencesTherault, David; Maharishi Ayur-Ved International, Inc.Welling, Steve; Nature’s Herbs

Meeting #3, April 26, 1996, San Francisco, CA

Brandt, Muriel; American Dietetic AssociationCalloway, Doris H.; University of California, BerkeleyHobbs, Christopher; HerbalistIkeda, Joanne P.; University of California, BerkeleyKallman, Burton; National Nutritional Foods AssociationLaux, Marcus; Licensed Naturopathic Physician

D-2 Commission on Dietary Supplement Labels

McGuffin, Michael; American Herbal Products AssociationO’Leary, Tom; Rainbow Light Nutritional SystemsPizzorno, Joseph E., Jr.; Bastyr UniversityReinhardt, Jeffrey H.; People For Pure FoodRiedel, Karl; Nature’s LifeSchauss, Alexander G.; Citizens For HealthSchiff, Paula; ConsumerStemet, John; Citizens for HealthUpton, Roy; American Herbalists GuildWhitman, James; Shaklee Corporation

Meeting #4, June 6, 1996, Orlando, FL

Baker, Dennis; Association of Food and Drug OfficialsCamire, Mary Ellen; Institute of Food TechnologistsCrawford, Bob; State of Florida, Dept. of Agriculture and Consumer ServicesGirardi, Frank A.; Hoffmann-La Roche Inc.Hildwine, Regina; National Food Processors AssociationJahner, Debra K.W.; NutriliteLawhead, Clara; State of Florida, Dept. of Health and Rehabilitative ServicesMartinez, Antonio C., II; Nutritional Health AllianceMilner, John A.; American Society for Nutritional SciencesPazder, Nadine; American Dietetic AssociationSilverglade, Bruce; Center for Science in the Public InterestTrinker, Deborah; Rexall Sundown, Inc.Woodward, Betsy B.; State of Florida, Dept. Of Agriculture and Consumer Services

Meeting #5, September 19-20, 1996, Reston, VA

Isrealsen, Loren D.; Utah Natural Products AllianceMustafa, Anne; Food and Drug AdministrationPeeler, C. Lee; Federal Trade Commission

Meeting #6, October 24-25, 1996, Washington, DC

No oral testimony presented

Meeting #7, December 16, 1996, Washington, DC

No oral testimony presented

Commission on Dietary Supplement Labels D-3

Meeting #8, March 4, 1997, Baltimore, MD

Chernoff, Ronni; American Dietetic Association Cordaro, John; Council for Responsible NutritionFord, Michael Q.; Israelsen, Loren D.; Young, Anthony; jointly for American Herbal ProductsAssociation, National Nutritional Foods Association, and Utah Natural Products AllianceHildwine, Regina; National Food Processors AssociationMartinez, Antonio C., II; Nutritional Health AllianceMilner, John A.; American Society for Nutritional SciencesSilverglade, Bruce; Center for Science in the Public Interest

Appendix E

INDIVIDUALS AND ORGANIZATIONS PROVIDING

WRITTEN SUBMISSIONS TO THE COMMISSION

Commission on Dietary Supplement Labels E-1

INDIVIDUALS AND ORGANIZATIONS PROVIDING

WRITTEN SUBMISSIONS TO THE COMMISSION

Harunobu Amagase, Ph.D. Robert E. DrobyshewskiManager, Research and Development Attica Correctional FacilityWakunaga of America Co., Ltd P.O. Box 14923501 Madero Attica, NY 14011-0149Mission Viejo, CA 92691-2764

Holly Bayne 1350 E. Flamingo Ave.Traditional Medicines Research Project Las Vegas, NV 89119American Botanical CouncilP.O. Box 201660 Michael Q. FordAustin, TX 78720-1660 Executive Director

Paula Benedict, M.P.H., R.D. 3931 MacArthur Blvd., Suite 101Coordinator Newport Beach, CA 92660Nutrition Quackery Prevention Task Force351 North Mt. View Avenue Linnie A. Friedlander, C.P.A.San Bernardino, CA 92415-0010 31340 Hilliard Blvd.

Helen B. Black, R.D.5855 Skyline Blvd. Debra GoldsteinOakland, CA 94611 Council of Better Business Bureaus, Inc.

Anthony L. Blank New York, NY 10022Director, Clinical Studies4 Health, Inc. Peter Greenwald, M.D.5485 Conestoga Court DirectorBoulder, CO 80301 Division of Cancer Prevention and Control

Virginia H. Britton National Cancer Institute1375 Pershing Blvd. #D-10 Bethesda, MD 20892Reading, PA 19607-1457

Jack E. Byrd Law Offices of Christopher E. GrellP.O. Box 159 The Monadnock BuildingHardy, VA 24101-0159 685 Market Street

Kenneth J. Carpenter, Ph.D. San Francisco, CA 94105Professor EmeritusDepartment of Nutritional Sciences Gary A. Henderson, Ph.D.University of California Director, Scientific RelationsBerkeley, CA 94720-3104 Kraft Foods, Inc.

Nancy M. Childs, Ph.D. White Plains, NY 10625Assistant Professor of Food MarketingSaint Joseph5600 City AvenuePhiladelphia, PA 19131-1395

Bernard Farr

National Nutritional Foods Association

Westlake, OH 44145

845 Third Avenue


Christopher E. Grell

Suite 540

250 North Street

E-2 Commission on Dietary Supplement Labels

Victor Herbert, M.D., J.D. Professor and HeadProfessor of Medicine Department of Nutrition and Graduate NYU-Mount Sinai School of Medicine Program in NutritionHematology & Nutrition Research 126 Henderson Building South Laboratory The Pennsylvania State UniversityVeterans Affairs Medical Center University Park, PA 16802-0001130 West Kingsbridge RoadBronx, New York 10468-3922 Judi S. Morrill, Ph.D.

Loren D. Israelsen San Jose State UniversityExecutive Director One Washington SquareUtah Natural Products Alliance San Jose, CA 95192-00582046 E. Murray Holladay Road, Suite #204Salt Lake City, UT 84117-5173 Jeffrey Morrison

Rosemary Jacobs American Herbal Products AssociationP.O. Box 1033 P.O. Box 30585Derby Line, VT 05830 Bethesda, MD 20814

Ruth Kava, Ph.D., R.D. Rebecca Mullis, Ph.D., R.D.Director of Nutrition PresidentElizabeth M. Whelan, Sc.D., M.P.H., President Society for Nutrition EducationAmerican Council on Science and Health 2001 Killebrew Drive, Suite 3401995 Broadway Minneapolis, MN 55425-1882New York, NY 10023-586

Marie L. Knerr Regional Drug AgentP.O. Box 1595 Department of Health and RehabilitativeBig Bear City, CA 92314 Services

Maureen Mackey, Ph.D. 905 E. Martin Luther King Blvd., Suite 340Director, Nutritional Science Tarpon Springs, FL 34689Worldwide Regulatory AffairsMonsanto Company Patricia Park1751 Lake Cook Road The Foundation for Innovation in MedicineDeerfield, IL 60015 595 Madison Avenue

Michelle MarcotteMarcotte Consulting Sandra C. Raymond443 Kintyre Private Executive DirectorOttawa, Ontario, K2C 3M9 National Osteoporosis FoundationCanada 1150 17 Street, N.W., Suite 500

Lani L. MilnerP.O. Box 1828 Claire Regan, M.S., R. D.Big Bear City, CA 92314-1828 Grocery Manufacturers of America

John A. Milner, Ph.D. Chief, Food and Drug Branch

Department of Nutrition and Food Science

Executive Director

Deborah A. Orr, R.PH.

Office of Drug Control

New York, NY 10022

th

Washington, D.C. 20036-4306

1010 Wisconsin Ave., N.W.Suite 900Washington, DC 20007

Stuart E. Richardson, Jr. M.P.H.

Commission on Dietary Supplement Labels E-3

Department of Health Services New Port Richey, FL 34653-1399714/744 P StreetP.O. Box 942732 Jean TownsendSacramento, CA 94234-7320 1024 Cranbrook Ave.

Deadra Rose Rubin2906 Santa Clara Ave. Roy UptonAlameda, CA 94501 Vice-President, Legislative Liaison

Mark Silbergeld, Co-Director P.O. Box 746555Marsha N. Cohen, Consultant Arvada, COConsumers Union1666 Connecticut Avenue, Suite 310 Patrice B. Wright, Ph.D.Washington, DC 20009-1039 Director, Pharmacology & Toxicology

Food and Nutrition Labeling Group Associationc/o Bruce Silverglade 1150 Connecticut Avenue, NWDirector of Legal Affairs Washington, DC 20036Center for Science in the Public Interest1875 Connecticut Avenue, N.W., Suite 300Washington, DC 20009-5728

A. Elizabeth Sloan, Ph.D.PresidentApplied Biometrics631 U.S. Highway One, Suite 406North Palm Beach, FL 33408

Jeffery Sobal, Ph.D., M.P.H.Associate ProfessorDivision of Nutritional SciencesCornell UniversityMartha Van Rensselaer HallIthaca, NY 14853-4401

Bert Spiker, Ph.D., M.D.PresidentOrphan Medical, Inc.13911 Ridgedale Drive, Suite 475Minnetonka, MN 55305

Paul SweetPresidentNational Policy Strategies314 Massachusetts Ave., N. E.Washington, DC 20002

Beatrice D. Taylor525 Salem Ave.Franklinville, NJ 08322-3340

Barbara Toth, R.N., B.S.N.Ridgewood High School7650 Orchid Lake Road

Torrance, CA 90503-5106

American Herbalists Guild

Nonprescription Drug Manufacturers

APPENDIX F

ACRONYMS

Commission on Dietary Supplement Labels F-1

ACRONYMS

AIDS Acquired immune deficiency syndrome ANPR Advance Notice of Proposed RulemakingCFR Code of Federal RegulationsCTFA Cosmetic, Toiletry and Fragrance Association, Inc.DSHEA Dietary Supplement Health and Education Act of 1994 DV Daily Value FASEB Federation of American Societies for Experimental Biology FDA Food and Drug AdministrationFDCA Federal Food, Drug, and Cosmetic Act of 1938FEMA Flavor and Extract Manufacturers Association FTC Federal Trade Commission GMP Good Manufacturing Practice GRAS Generally recognized as safeHHS Department of Health and Human Services HNRIMS Human Nutrition Research and Information Management System LSRO Life Sciences Research OfficeMDR Minimum Daily RequirementNIH National Institutes of Health NLEA Nutrition Labeling and Education Act of 1990 ODS Office of Dietary Supplements OTC Over-the-counter PDP Principal Display Panel RDI Reference Daily Intake USP U.S. Pharmacopeia U.S. RDA U.S. Recommended Daily AllowanceWHO World Health Organization

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