Food Labeling: Health Claims; Antioxidant Vitamins C and E and the Risk in Adults of Atherosclerosis, Coronary Heart Disease, Certain Cancers, and Cataracts

SUMMARY: The Food and Drug Administration (FDA) is issuing an interim

final rule to prohibit the use on foods of a claim relating to the

relationship between antioxidant vitamins C and E and the risk in

adults of atherosclerosis, coronary heart disease, certain cancers, and

cataracts. This rule is in response to a notification of a health claim

submitted under section 303 of the FDA Modernization Act of 1997

(FDAMA). FDA has reviewed statements that the petitioner submitted in

that notification, and, in conformity with the requirements of FDAMA,

the agency is prohibiting the claim because the statements submitted as

the basis of the claim are not ``authoritative statements'' of a

scientific body, as required by FDAMA; therefore, section 303 of FDAMA

does not authorize use of this claim. As provided for in section 301 of

FDAMA, this rule is effective immediately upon publication.

DATES: The interim final rule is effective June 22, 1998; comments by

September 8, 1998.

ADDRESSES: Submit written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,

Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Christine J. Lewis, Center for Food

Safety and Applied Nutrition (HFS-451), Food and Drug Administration,

200 C St. SW., Washington, DC 20204, 202-205-4168.

SUPPLEMENTARY INFORMATION:

I. The FDA Modernization Act of 1997

On November 21, 1997, the President signed FDAMA into law (Pub. L.

105-115), which amended the Federal Food, Drug, and Cosmetic Act (the

act). Sections 303 and 304 of FDAMA amended section 403(r)(2) and

(r)(3) of the act by adding new paragraphs (r)(2)(G), (r)(2)(H),

(r)(3)(C), and (r)(3)(D) to section 403 of the act (21 U.S.C.

343(r)(2)(G), (r)(2)(H), (r)(3)(C), and (r)(3)(D), respectively), which

provide for the use in food labeling of nutrient content claims and

health claims, respectively, based on authoritative statements. These

provisions of FDAMA supplement the petition process for nutrient

content and health claims provided by section 403(r)(4) (21 U.S.C.

343(r)(4)) and Secs. 101.69 and 101.70 (21 CFR 101.69 and 101.70,

respectively) by providing an alternative for establishing the

scientific basis for such claims by reliance on authoritative

statements.

FDAMA requires that a notification of the prospective nutrient

content claim or the prospective health claim be submitted to FDA at

least 120 days before a food bearing the claim may be introduced into

interstate commerce. The notification must contain specific information

including: (1) The exact wording of the prospective nutrient content

claim or health claim; (2) a concise description of the basis upon

which the petitioner relied for determining that the requirements of

section 403(r)(2)(G)(i) of the act for nutrient content claims or

section 403(r)(3)(C)(i) for health claims have been satisfied; (3) a

copy of the authoritative statement that serves as the basis for the

claim; and (4) a balanced representation of the scientific literature

relating to the nutrient level for a prospective nutrient content claim

or relating to the relationship between the nutrient and the disease or

health-related condition for a prospective health claim. For a

prospective nutrient content claim, the authoritative statement must

identify the nutrient level to which the claim refers. For a

prospective health claim, the authoritative statement must be a

statement about the relationship between a nutrient and a disease or

health-related condition to which the claim refers. For both types of

claims, the authoritative statement must be currently in effect and it

must have been published either by a scientific body of the U.S.

Government that has official responsibility for public health

protection or research directly relating to human nutrition (e.g., the

National Institutes of Health (NIH) or the Centers for Disease Control

and Prevention (CDC)) or by the National Academy of Sciences (NAS) or

any of its subdivisions (hereinafter referred to as a ``scientific

body'').

Under new section 403(r)(2)(H) and (r)(3)(D) of the act, such a

claim may be made beginning 120 days after submission of the

notification until: (1) FDA has issued an effective regulation that

prohibits or modifies the claim; (2) the agency has issued a regulation

finding that the requirements under section 403(r)(2)(G) for a

prospective nutrient content claim or under section 403(r)(3)(C) for a

prospective health claim have not been met; or (3) a district court of

the United States in an enforcement proceeding under chapter III of the

act has determined that the requirements under section 403(r)(2)(G) for

a prospective nutrient content claim or under section 403(r)(3)(C) for

a prospective health claim have not been met. During the 120 days

following submission of a notification and before the claim may appear

on a food, the agency may also notify any person who is making the

claim that the notification did not include all of the required

information.

Section 304 of FDAMA permits nutrient content claims based on

authoritative statements for both conventional foods and for dietary

supplements because section 304 amended section 403(r)(2) of the act,

which provides for nutrient content claims on both conventional foods

and dietary supplements. Section 303 of FDAMA does not include

provisions for health claims for dietary supplements based on

authoritative statements, however. In particular, section 403(r)(5)(D)

of the act (21 U.S.C. 343(r)(5)(D)) specifies that health claims for

dietary supplements shall not be subject to section 403(r)(3) of the

act, but rather to a procedure and standard that FDA establishes by

regulation. In section 303 of FDAMA, Congress amended section 403(r)(3)

of the act, which provides for procedures and standards for health

claims for conventional foods, to allow for health claims based on

authoritative statements for conventional foods, but Congress did not

amend section 403(r)(5)(D) of the act.

Therefore, FDA believes that section 403(r)(3)(C) of the act

authorizes use of a health claim based on an authoritative statement

only on any conventional food that provides an appropriate level of the

nutrient that is the subject of the health claim, that does not exceed

the disqualifying levels identified in Sec. 101.14(a)(5) (21 CFR

101.14(a)(5)), and that otherwise complies with section 403(r)(3)(C)

and all other provisions of the act. Nevertheless, FDA has tentatively

concluded that, for health claims authorized via the authoritative

statement procedure provided by FDAMA, conventional foods and dietary

supplements should be subject to the same standards and procedures.

This position is consistent with the agency's final rule that made

dietary supplements subject to the same general

[[Page 34085]]

requirements as apply to conventional foods with respect to health

claims (59 FR 395, January 4, 1994). This approach is also consistent

with the guidance of the Commission on Dietary Supplement Labels, which

stated in its 1997 report (Ref. 1) that the process for the approval of

health claims should remain the same for dietary supplements and

conventional foods. Therefore, FDA intends to issue a proposed rule to

provide for health claims based on authoritative statements for dietary

supplements.

A. Authoritative Statements

Sections 303 and 304 of FDAMA authorize the use of a health or

nutrient content claim based, in part, on an ``authoritative

statement.'' In particular, new section 403(r)(3)(C)(i) and

(r)(2)(G)(i) of the act states that such claims are authorized and may

be made when ``a scientific body * * * has published an authoritative

statement, which is currently in effect.'' For a health claim, section

403(r)(3)(C)(i) of the act requires that the statement must be ``about

the relationship between a nutrient and a disease or health-related

condition to which the claim refers.'' For a nutrient content claim,

section 403(r)(2)(G)(i) of the act requires that the statement must be

one ``that identifies the nutrient level to which the claim refers.''

Section 403(r)(3)(C) and (r)(2)(G) of the act further requires

that:

* * * [a] statement shall be regarded as an authoritative

statement of a scientific body described in subclause (i) only if

the statement is published by the scientific body and shall not

include the statement of an employee of the scientific body made in

the individual capacity of the employee.

Although Congress did not explicitly define the term

``authoritative statement,'' section 403(r)(3)(C) and (r)(2)(G) of the

act and the legislative history clarify several characteristics that

Congress intended an ``authoritative statement'' to have. Most

significantly, to be the basis for a health or nutrient content claim,

a statement must: (1) Address certain subjects, namely, for a health

claim, it must be about the relationship between a nutrient and a

disease or health-related condition to which the claim refers, or, for

a nutrient content claim, it must identify the nutrient level to which

the claim refers; (2) be published by an appropriate scientific body

and represent its official position, and may not be, for example, a

statement of individual employees of the scientific body made in the

individual capacities of the employees; (3) be based on a deliberative

review of the scientific evidence on the subject of the statement and

not indicate that the scientific evidence about the subject of the

statement is preliminary or inconclusive; and (4) be currently in

effect. The aspects of these requirements relevant to this rulemaking,

and its companion rulemakings publishing elsewhere in this issue of the

Federal Register, are discussed in greater detail in section I.A.1 of

this document.

1. To Be the Basis for a Health or Nutrient Content Claim, a Statement

Must Address One of Two Subjects

For a statement to be eligible for consideration as an

``authoritative statement,'' it must address certain subjects. Section

403(r)(3)(C) of the act provides that, for a health claim, it must be

``about the relationship between a nutrient and a disease or health-

related condition to which the claim refers.'' Section 403(r)(2)(G) of

the act provides that, for a nutrient content claim, it must ``identify

the nutrient level to which the claim refers.''

There are several aspects to these requirements. First, a statement

cannot be an ``authoritative statement'' under section 403(r)(2)(G) or

(r)(3)(C) of the act if it identifies no nutrient level or if it is not

about the relationship between a nutrient and a disease or health-

related condition. For example, if a statement refers to no nutrient,

to no disease or health-related condition, or to neither a nutrient nor

a disease or health-related condition, it cannot be an authoritative

statement under section 403(r)(3)(C) of the act. Second, if a statement

is ``about the relationship between a nutrient and a disease or health-

related condition,'' or if it ``identif[ies] the nutrient level,'' it

must be about the relationship or nutrient ``to which the claim

refers.'' Moreover, the statement must be about the relationship

between a nutrient and a disease or health-related condition in humans

or it must identify a nutrient level for total daily consumption by

humans.

When evaluating what relationship a statement is about, or what

nutrient level a statement identifies, it may be necessary to consider

the context in which the statement appears. It is likely that a

submitter will identify excerpted sentences as an ``authoritative

statement.'' The context in which these excerpted sentences appears can

be relevant when determining the subject of the statement. For example,

sentences immediately adjoining the excerpted sentences or in a summary

statement in the document may clarify the disease that is the subject

of the excerpted sentences.

Accordingly, the statutory requirement in section

403(r)(3)(C)(ii)(II) and (r)(2)(G)(ii)(II) of the act that a

notification include ``a copy of the statement referred to in subclause

(i) upon which [the] person [who submitted the notification] relied in

making the claim,'' means that the entire document from which the

statement is excerpted should be included in a notification. The agency

notes that submission of the entire document is also relevant to other

determinations under section 403(r)(3)(C) and (r)(2)(G), such as

whether the scientific evidence about the relationship or nutrient

level at issue is preliminary or inconclusive, as discussed in section

I.A.3 of this document, and whether a health or nutrient content claim

is ``stated in a manner so that the claim is an accurate representation

of the authoritative statement referred to in subclause (i),'' as

required by section 403(r)(3)(C)(iv) and (r)(2)(G)(iv) of the act.

2. To Be the Basis for a Health or Nutrient Content Claim, a Statement

Must Be Published by an Appropriate Scientific Body and Represent the

Official Policy of That Body.

Section 403(r)(3)(C) and (r)(2)(G) of the act requires that an

``authoritative statement'' be ``published.'' The agency understands

the use of ``published'' in section 403(r)(3)(C)(i) and (r)(2)(G)(i) to

mean that the statement must be publicly available in print form (paper

or electronic).

The identical last sentence of section 403(r)(3)(C) and (r)(2)(G)

of the act states that:

* * * [a] statement shall be regarded as an authoritative

statement of a scientific body described in subclause (i) only if

the statement is published by the scientific body and shall not

include the statement of an employee of the scientific body made in

the individual capacity of the employee.

``Published'' as used in this sentence means that the scientific body

can be considered to be the author of the statement, in that the

statement represents the official policy of the scientific body. Of

course, the statements of scientific bodies--indeed, of organizations

generally--are authored by individuals. Yet statements that are merely

those of individual employees made in the individual capacities of the

employees are not statements that have been authored by, and so

represent the official policy of, the scientific body. Similarly, in

the case of Federal scientific bodies with subdivisions, such as NIH

and CDC, section 403(r)(3)(C) and (r)(2)(G) indicates that the

scientific body, and not merely the subdivision, can be considered to

have ``published'' a statement within the

[[Page 34086]]

meaning of those sections only if, as the legislative history

indicates, ``statements issued by entities such as NIH and CDC reflect

consensus within those institutions'' (H. Conf. Rept. 105-399, at 98

(1997)). Accordingly, to be considered an ``authoritative statement''

under section 403(r)(3)(C) and (r)(2)(G), a statement must represent

the official policy of a scientific body.

3. To Be the Basis for a Health or Nutrient Content Claim, a Statement

Must Be Based on a Deliberative Review of the Scientific Evidence on

the Subject of the Statement, and It Should Not Indicate That the

Scientific Evidence Is Preliminary or Inconclusive

In section 403(r)(3)(C)(i) and (r)(2)(G)(i) of the act, Congress

required that claims may be authorized only when ``a scientific body *

* * has published an authoritative statement,'' not merely when a

scientific body has published a statement (emphasis added). The use of

``authoritative'' here indicates that a statement may not be the basis

for a health or nutrient content claim merely because its source is a

scientific body, an authority on the subject of the statement. A review

of the legislative history of sections 303 and 304 of FDAMA indicates

that, to be ``authoritative,'' Congress intended that a statement must

be the product of a deliberative review of the scientific evidence on

the subject of the statement. In addition, the statement should not

indicate that the scientific evidence about the subject of the

statement is preliminary or inconclusive.

Congress intended both that claims based on authoritative

statements should have ``a presumption of validity'' (H. Rept. 105-306,

at 16 and 17 (1997)) and that ``more scientifically sound nutrition

information * * * be provided to consumers through health and nutrient

content claims'' based on authoritative statements (H. Conf. Rept. 105-

399, at 98 (1997) (emphasis added); see also H. Rept. 105-306, at 16

(1997) and S. Rept. 105-43, at 49 (1997)).

When FDA authorizes a health claim by regulation under section

403(r)(3)(B) of the act or establishes a Daily Value that can serve as

the basis for a nutrient content claim, it conducts a deliberative

review of the scientific evidence about the relationship between a

nutrient and a disease or health-related condition or about the

nutrient level at issue and concludes that there is significant

scientific agreement about the relationship or appropriate scientific

consensus about the nutrient level. Congress intended that an

``authoritative statement'' published by a scientific body could be the

basis for health and nutrient content claims because the

``authoritative statement'' is to serve as a presumptive surrogate for

FDA's deliberative review of the scientific evidence.

Congress therefore intended that an ``authoritative statement''

must be the product of a deliberative review of the scientific evidence

on the subject of the statement. For example, the House Report states

that:

[a]uthoritative scientific bodies, as part of their official

responsibilities for public health protection, regularly undertake

deliberative reviews of the scientific evidence to evaluate

potential diet/disease relationships, and issue authoritative

statements concerning such relationships.

(H. Rept. 105-306, at 16 (1997)). The Senate Report repeats this idea,

noting that scientific bodies engage in:

* * * deliberative processes * * * in issuing statements on

matters of public health. Important Federal public health

organizations, as part of their official responsibilities, routinely

review the scientific evidence pertinent to diet and disease

relationships, and publish statements developed through such

reviews.

(S. Rept. 105-43, at 49 (1997)).

Moreover, only a statement that a relationship between a nutrient

and a disease or health-related condition exists or that identifies a

level of a nutrient--and not merely statements about a possible

relationship or level--can serve as the basis for claims that will

provide consumers with scientifically sound information. Only a claim

based on such a statement can be accorded a presumption of validity.

Accordingly, a statement that indicates, for example, that research

about a nutrient level or a relationship between a nutrient and a

disease or health-related condition is preliminary or inconclusive,

that indicates that such a relationship or a nutrient level is or

should be the subject of ongoing scientific study, or that indicates

the direction for future research about such a relationship or a

nutrient level is not ``authoritative.'' When evaluating whether a

statement about a relationship or nutrient level indicates that the

scientific evidence is preliminary or inconclusive, the agency intends

to consider the context in which the statement appears, as discussed in

section I.A.1 of this document. For example, a statement of excerpted

sentences might not indicate that research is preliminary or that there

are unresolved questions that require additional study, but such

qualifiers could be found elsewhere in the document.

The agency notes that, even if a statement meets the criteria to

be an ``authoritative statement,'' Congress also provided under new

section 403(r)(3)(D)(i) of the act that FDA have the authority to

prohibit a health claim based on an authoritative statement when there

is not significant scientific agreement that there is a relationship

between the nutrient and the disease or health-related condition in

question. As the Senate Report on the provision explains, in an agency

rulemaking to prohibit or modify a health claim based on an

authoritative statement, ``the standards and criteria for health claims

prescribed by section 403(r)(3) and implementing regulations, including

the significan[t] scientific agreement standard, would be fully

applicable'' (S. Rept. 105-43, at 51 (1997); see also H. Rept. 105-306,

at 15 (1997)).

With respect to nutrient content claims, Congress indicated that

the agency is to determine ``whether the authoritative statement upon

which the notification is based is supported by scientific consensus to

the extent * * * appropriate to allow the claim'' (H. Rept. 105-306, at

17-18 (1997)), an evaluation that FDA would make under section

403(r)(2)(H) of the act, after the Federal scientific body that is the

source of a statement determines that the statement reflects consensus

within it, as discussed in section I.A.2 of this document.

B. Review Process

As allowed by sections 303 and 304 of FDAMA, health claims and

nutrient content claims based on authoritative statements from Federal

scientific bodies or NAS may be made on foods in interstate commerce as

soon as 120 days after submission of a notification of the claim to

FDA. Upon receipt of a notification, FDA intends to review the

notification to determine whether the components specified in section

403(r)(2)(G) and (r)(3)(C) are present within the submission packet.

When such components are missing, FDA intends to notify the submitter

by letter identifying one or more of these components that is absent

from the notification packet.

If the necessary components are present, FDA intends to determine,

for a health claim, what relationship between a nutrient and disease or

health-related condition is at issue, or, for a nutrient content claim,

what nutrient is at issue. If, by regulation under section 403(r)(3)(B)

of the act, the agency has already authorized a health claim about the

relationship at issue, then the notification provisions of section

403(r)(3)(C) of the act may not be used to modify the existing health

claim or to authorize the prospective health claim. Similarly, if by

rulemaking the

[[Page 34087]]

agency has already established a Daily Value for the nutrient at issue,

then the notification provisions of section 403(r)(2)(G) of the act may

not be used to modify the existing Daily Value. Instead, a health claim

about the relationship at issue or a nutrient content claim referring

to the nutrient at issue may be made when the claim is consistent with

the existing health claim regulation or with the established Daily

Value and the authorized terms for nutrient content claims.

Furthermore, if the prospective claim refers to a relationship or a

nutrient that is not addressed by the statement that is identified as

the ``authoritative statement'' on which the claim is based, then

section 403(r)(3)(C) and (r)(2)(G) of the act does not authorize the

health or nutrient content claim at issue. In each case, FDA intends to

notify the submitter by letter that use of the claim is not authorized

under section 403(r)(3)(C) or (r)(2)(G) of the act, as appropriate.

If, however, a prospective claim could be authorized based on an

appropriate authoritative statement, and if the prospective claim

refers to a relationship or nutrient that is addressed by the statement

that is identified in the notification as the ``authoritative

statement,'' FDA then intends to evaluate further whether the statement

is an ``authoritative statement.'' In particular, FDA intends to

determine for a statement, as a threshold matter, whether: (1) It may

be attributable to a scientific body or to one or more of its

employees; (2) it is publicly available in print form (paper or

electronic); and (3) the statement indicates that the scientific

evidence about the relationship between a nutrient and a disease or

health-related condition or a nutrient level is preliminary or

inconclusive. With respect to the first of these issues, FDA notes that

it can determine that a statement from a non-Federal body or agency--

such as a state university school of public health--is not an

``authoritative statement,'' or that a statement from a scientist who

was not an employee of an appropriate scientific body is not an

``authoritative statement.'' As a general matter, however, only a

scientific body can state whether a statement that is attributable to

it or to one or more of its employees actually represents the official

policy of the scientific body or not, and FDA would therefore consult

with the scientific body if necessary.

If a statement fails to meet any of these criteria, FDA would

normally conclude that the statement is not an authoritative statement.

In any case the agency may, and, when a statement meets these three

criteria, the agency would normally, consult with the scientific body

to which the statement is attributed. FDA would request that the

scientific body determine, for example, whether the statement is

currently in effect; whether the statement represents the official

policy of the scientific body, for example, by reflecting consensus

within that body, as opposed to being the statement of individual

employees made in the individual capacities of those employees; and

whether the statement is based on a deliberative review of the

scientific evidence.

If the statement is found to be issued by an appropriate scientific

body and determined to be an ``authoritative statement'' under section

403(r)(2)(G) or (r)(3)(C) of the act, the agency intends to review the

wording of the claim to determine if it is in accordance with section

403(r)(3)(C)(iv) or (r)(2)(G)(iv) of the act. These provisions of the

act require that the claim be stated in a manner so that it is an

accurate representation of the authoritative statement and so that the

claim enables the public to comprehend the information provided in the

claim and to understand the relative significance of such information

in the context of a total daily diet.

For health claims, FDA also intends to consider the requirement of

section 403(r)(3)(C)(iii) of the act that there be compliance with, for

example, sections 403(a) and 201(n) of the act (21 U.S.C. 321(n)),

which require that the claim be truthful and not misleading, including

compliance as appropriate with existing Sec. 101.14. FDA would also

determine whether there is significant scientific agreement concerning

the authoritative statement, as provided for under new section

403(r)(3)(D)(i) of the act. For nutrient content claims, FDA intends to

consider the requirements of section 403(r)(2)(G)(iii) of the act that

there be compliance with, for example, section 403(r)(2)(A)(i) of the

act, which requires that nutrient content claims use the terms defined

in FDA's regulations, and sections 403(a) and 201(n) of the act,

including compliance as appropriate with existing Sec. 101.13 (21 CFR

101.13). If, after this review, FDA has no objections to the claim,

then the statute provides that the claim may be used on food labels 120

days after submission of a complete notification.

By contrast, if the statement is not from an appropriate scientific

body or is found not to be an ``authoritative statement'' from a

Federal scientific body or NAS (or any of its subdivisions), the agency

intends to determine that the notification does not meet the

requirements of section 403(r)(3)(C) or (r)(2)(G) of the act in that

the submitter has not submitted a statement from a Federal scientific

body or NAS, or an authoritative statement from such a body. The agency

may notify the submitter of this determination, and its basis, by

letter. Alternatively, the agency may issue an interim final rule to

prohibit the claim.

Generally, the agency would notify the submitter by letter when,

for example, the notification is deficient on its face, and the agency

would use the rulemaking process when substantial scientific or legal

questions are presented by the notification. The agency intends to

elaborate further on these issues in implementing regulations. The

agency has chosen to respond with nine interim rules publishing in this

issue of the Federal Register to a notification for nine claims to

specify the approach used by the agency to review this notification in

the absence of implementing regulations, and to provide opportunity for

public comment. In the future, the agency anticipates that it may

respond to similar notifications by letter. Whether FDA sends a letter

or acts by rulemaking to prohibit a claim, the agency may begin an

enforcement action under the act in a U. S. district court if such a

claim is used in food labeling.

The agency notes that, when it sends such a letter or acts by

regulation to prohibit the use of a claim, a person nonetheless may

submit in the future a notification that bases the claim on a statement

that meets the requirements of section 403(r)(3)(C) or (r)(2)(G) of the

act. If there is no authoritative statement that may serve as a basis

for the claim, an interested person may petition the agency under

section 403(r)(4) of the act and Sec. 101.70 to authorize the health

claim by regulation under section 403(r)(3)(B) of the act. For a

nutrient content claim, an interested person may submit a citizen

petition under 21 CFR 10.30 that requests the agency to establish the

Daily Value to which the claim would refer.

II. The Notification

Section 403(r)(2)(G) and (r)(3)(C) of the act became effective on

February 19, 1998. On February 23, 1998, the agency received a

notification from Weider Nutrition International, Inc., containing nine

prospective claims that were identified in the text of the notification

as health claims (Ref. 2). The notification included statements that

the submitter described as authoritative statements and a scientific

literature review for each claim. FDA has created nine separate

dockets, one for each of

[[Page 34088]]

the nine claims and is issuing a separate interim final rule responding

to each claim.

This interim final rule addresses the first claim in the

notification. The notification included six statements that the

petitioner identified as authoritative statements on which the

following claim is based: ``Antioxidant vitamins C and E may reduce the

risk in adults of atherosclerosis, coronary heart disease, certain

cancers, and cataracts. Sources of Vitamin C and E include fruits,

vegetables, and dietary supplements.''

The first sentence of this claim will be discussed in greater

detail in section III of this document. FDA notes that this claim

describes the relationship between vitamins C and E and a number of

different diseases and, thus, in point of fact, reflects several

prospective health claims. The second sentence, ``Sources of Vitamin C

and E include fruits, vegetables, and dietary supplements,'' is not a

health claim. Given that the notification indicated that it was

intended to be a notification for health claims, this statement was not

reviewed by FDA. The submitter did not separately identify this

statement as any particular type of claim.

Nonetheless, as a point of information, the agency wishes to

highlight that statements that appropriately constitute nutrient

content claims are allowed on labels and in the labeling of foods and

dietary supplements. Moreover, statements that constitute dietary

guidance are also allowed provided the information is truthful and not

misleading as required by sections 403(a) and 201(n) of the act.

With respect to nutrient content claims, FDA concluded in comment

152 of its final rule for nutrient content claims (58 FR 2302 at 2345,

January 6, 1993) that the term ``source'' alone merely connotes that a

nutrient is present and does not provide consumers with meaningful

information about the level of the nutrient. Therefore, FDA did not

define the term ``source,'' although it did define several other terms

that include the word ``source.'' For example, a food is defined as a

``good source'' of a nutrient if it contains 10 to 19 percent of the

Reference Daily Intake (RDI) for that nutrient per reference amount

customarily consumed (Sec. 101.54(c) (21 CFR 101.54(c))), or as an

``excellent source'' if it contains 20 percent or more of a nutrient's

RDI per reference amount customarily consumed (Sec. 101.54(b)). In

addition, ``trivial source'' is defined as a synonym for ``free'' and

``low source'' as a synonym for ``low'' (see, for example, 21 CFR

101.61(b)(1) and (b)(4)).

Information regarding the agency's position on nutrient content

claims is included in the preamble to the proposed and final rules for

nutrient content claims (56 FR 60421, November 27, 1991, and 58 FR

2302, January 6, 1993) and in the agency guidance document, ``Food

Labeling--Questions and Answers--Volume I--For Guidance to Facilitate

the Process of Developing or Revising Labels for Foods Other than

Dietary Supplements'' (Ref. 3).

As for statements that constitute dietary guidance, such label

information must be truthful and not misleading as discussed in section

II.D.6 of the preamble to the final rule for general requirements for

health claims (58 FR 2478 at 2487, January 6, 1993) and in the agency

guidance document, ``Food Labeling--Questions and Answers--Volume II--A

Guide for Restaurants and Other Retail Establishments'' (Ref. 4). The

agency notes that in the case of the subject sentence, not all fruits,

vegetables, and dietary supplements contain significant amounts of

vitamins C and E, and therefore if the statement were intended to

reflect dietary guidance it cannot be considered to be truthful and not

misleading. In addition, to be truthful and not misleading when used on

a particular food's labeling, that food must contain significant

amounts of vitamins C and E.

III. Basis for the Action

FDA has reviewed the notification submitted in support of the

prospective claim: ``Antioxidant vitamins C and E may reduce the risk

in adults of atherosclerosis, coronary heart disease, certain cancers,

and cataracts.'' The agency has determined that none of the six

statements submitted as the basis for this claim meets the requirements

in section 403(r)(3)(C) of the act to be an ``authoritative

statement.'' Because the prospective claim is not based on an

authoritative statement, it is not appropriate for the claim to appear

on food labels and labeling. Consequently, FDA is issuing this interim

final rule to prohibit the use of this claim. A discussion of the basis

for the agency's action on the notification follows.

First, FDA determined that the components required by section

403(r)(3)(C) of the act were present in the notification submitted to

support this claim. Second, FDA determined that, as a threshold matter,

each of the six statements cited in support of the claim may be

attributable either to an appropriate Federal scientific body or to an

employee or employees of such a body.

The notification in support of the claim that is the subject of

this document cites statements from: (1) A published article authored

by two employees of CDC; (2) public information provided on the

Internet by an institute of NIH; (3) an electronic version provided on

the Internet of ``Nutrition and Your Health: Dietary Guidelines for

Americans,'' (Home and Garden Bulletin No. 232, Fourth Edition, 1995)

(hereinafter, referred to as ``the dietary guidelines'')

recommendations developed by a group of Federal agencies and issued

jointly by the Department of Health and Human Services (DHHS) and the

United States Department of Agriculture (USDA); (4) public information

provided on the Internet by CDC's Office of Women's Health; (5) a NIH

press release provided on the Internet; and (6) an electronic version

provided on the Internet of a quarterly report from USDA's Agricultural

Research Service (ARS). Thus, the statements in the notification are

attributable to NIH, CDC, and USDA/ARS, as well as a group of Federal

agencies that included NIH, CDC, and USDA/ARS. Two of the scientific

bodies identified, NIH and CDC, are highlighted in the statute as

Federal scientific bodies. FDA believes that USDA/ARS is also a

scientific body of the U.S. Government with official responsibility for

public health protection or research directly relating to human

nutrition for the purposes of section 403(r)(2)(G) and (r)(3)(C) of the

act. The group that developed the dietary guidelines included Federal

agencies that are such scientific bodies. Accordingly, the statements

provided in the notification in support of the claim may be

attributable to appropriate Federal scientific bodies or to their

employees.

Finally, however, none of the six statements discussed in A.

through F. of this section of this document was found to be an

authoritative statement.

A. Statement 1

Statement 1 reads: ``Antioxidant micronutrients, especially

carotenes, vitamin C, and vitamin E, appear to play many important

roles in protecting the body against cancer. They block the formation

of chemical carcinogens in the stomach, protect DNA and lipid membranes

from oxidative damage, and enhance immune function.'' The notification

identified Statement 1 as an ``authoritative statement'' for purposes

of making the claim that is the subject of this rulemaking. The

statement is found in the conclusion section of an article published in

The Annual Review of Nutrition (12:139-59:1992), entitled: ``Dietary

Carotenes, Vitamin C, and Vitamin E as Protective Antioxidants in

[[Page 34089]]

Human Cancers,'' and authored by two persons, T. Byers and G. Perry,

who are identified in the article as employees of CDC at the time of

publication of the article. The Annual Review of Nutrition is published

periodically by Annual Reviews, Inc., in Palo Alto, CA. Editors for

each volume serve as reviewers for the various articles included in the

volume and contributors are asked to submit articles for consideration

for publication. The subject article is 20 pages of a review of the

literature that includes a section on the theoretical roles of dietary

oxidants in cancer prevention and focuses on the outcomes of laboratory

animal research and epidemiologic studies conducted since 1987. The

subject statement appears in the conclusion section of the paper. The

agency notes that the next sentence in the conclusion section states:

``Nevertheless, many important questions need to be answered before

either micronutrient supplements or food fortification can be

recommended as a cancer prevention strategy to the general

population.''

The noted qualifying sentence, as well as the wording of the

statement itself (i.e., ``appear to play''), suggests that the

scientific evidence about the relationship in question is preliminary

or inconclusive, as discussed in section I.A.3 of this document.

FDA asked CDC whether the statement is an ``authoritative

statement'' under FDAMA. CDC responded to FDA that the statement is not

an authoritative statement of CDC because it does not reflect consensus

within CDC and was not published by CDC (Ref. 5). CDC indicated that

the article was authored by individual employees made in the individual

capacity of those employees. Therefore, FDA has concluded that the

statement is not an ``authoritative statement'' under section

403(r)(3)(C) of the act because the statement was not published by CDC

and is instead the statement of individual employees of CDC made in

their individual capacities, as discussed in section I.A.2 of this

document.

B. Statement 2

Statement 2 reads: ``[Antioxidants] may help prevent disease.

Antioxidants fight harmful molecules called oxygen free radicals, which

are created by the body as cells go about their normal business of

producing energy * * * [Some] studies show that antioxidants may help

prevent heart disease, some cancers, cataracts, that are more common as

people get older.'' The notification identified Statement 2 as an

``authoritative statement'' for purposes of making the claim that is

the subject of this rulemaking. The statement is found within an

information piece entitled ``Life Extension: Science or Fiction?'' that

is provided on the Internet by the Administration on Aging and which

includes statements from the ``Age Page'' of the National Institute on

Aging (an Institute of NIH) (``http://www.aoa.dhhs.gov/aoa/pages/

agepages/lifextsn.html'' accessed on 12/2/97). This electronically

available information (submitted to the agency as a hardcopy reprint

from the Internet information) is dated 1994, is approximately two

standard printed pages in length, and is described as being intended to

inform the reader about chemicals being studied that may play a role in

aging and what scientists have learned about them so far. Topics

covered include antioxidants, deoxyribonucleic acid (DNA),

dehydroepiandrosterone (DHEA), and other hormones. Ten tips for healthy

aging are also included. The section on antioxidants is 14 sentences in

length and includes the three sentences identified as the subject

statement. The agency notes that the last sentence of the antioxidant

section is: ``More research is needed before specific recommendations

can be made.''

FDA asked NIH whether the statement is an ``authoritative

statement'' under FDAMA. NIH responded to FDA that the statement is not

an authoritative statement of NIH because it was prepared by an

individual from the National Institute on Aging and is not based on a

deliberative review of the scientific evidence regarding the nutrient-

disease relationship in question (Ref. 6). Therefore, FDA has concluded

that the statement is not an ``authoritative statement'' under section

403(r)(3)(C) of the act because it is not based on a deliberative

review of the scientific evidence, as described in section I.A.3 of

this document.

C. Statement 3

Statement 3 reads: ``The antioxidant nutrients found in plant

foods (e.g., vitamin C, carotenoids, vitamin E, and certain minerals)

are presently of great interest to scientists and the public because of

their potentially beneficial role in reducing the risk of cancer and

certain other chronic diseases.'' The notification identified Statement

3 as an ``authoritative statement'' for purposes of making the claim

that is the subject of this rulemaking. The statement is from an

electronic version of the dietary guidelines issued jointly by DHHS and

USDA and provided on the Internet (``http:www.usda.gov/fcs/library/

0102-1.txt'' accessed on 12/5/97). The submitted material consists of

selected pages reprinted from the Internet information, which

identifies the seven dietary guidelines and gives background

information on the use of, and reasons for, the guidelines. The dietary

guidelines reflect the findings of a panel of scientists concerning the

dietary recommendations to be made to the U.S. population, and the

guidelines are based on a deliberative review of the scientific

evidence about the nutrient/disease relationships that the guidelines

address. The subject statement is found within the discussion that

accompanies the recommendation to ``Choose a diet with plenty of grain

products, vegetables, and fruits.''

The statement indicates that a relationship between antioxidant

nutrients and cancer and other chronic disease is ``of great interest''

because of a ``potentially beneficial role.'' The statement points to

the need for future research and suggests that whether a relationship

exists should be the subject of scientific study, but does not indicate

that there exists a scientifically sound relationship that should be

accorded a presumption of validity. This assessment is further

supported by the fact that the subject of the dietary guidelines

recommendation that the text is intended to clarify is the dietary

importance of grain products, vegetables, and fruits, not the specific

impact of antioxidant nutrients, vitamins C and E, per se. FDA notes

that, consistent with the dietary guidelines, the agency has authorized

a health claim for the relationship between cancer and fruits and

vegetables that contain vitamin C (as well as vitamin A (as beta-

carotene) and dietary fiber) (21 CFR 101.78).

On this basis, FDA has concluded that the statement is not an

``authoritative statement'' under section 403(r)(3)(C) of the act

because the statement indicates that the scientific evidence about the

relationship in question is preliminary or inconclusive, as discussed

in section I.A.3 of this document.

The dietary guidelines is the product of a periodic review by a

group of Federal agencies, the most recent review having been completed

in 1995. FDA did not attempt to reconvene this group of Federal

agencies to consult with it about whether the statement is an

authoritative statement because, as discussed previously, the wording

and context of the statement show that it is not an authoritative

statement under section 403(r)(3)(C) of the act.

D. Statement 4

Statement 4 reads: ``A diet high in fiber, high in antioxidants,

and low in fat may play an important role in

[[Page 34090]]

preventing the development of atherosclerosis, coronary heart disease,

and some cancers.'' The notification identified Statement 4 as an

``authoritative statement'' for purposes of making the claim that is

the subject of this rulemaking. The statement is found in information

on ``Health in Later Years'' provided on the Internet by CDC's Office

of Women's Health in a section entitled: ``Health Problems among Older

Women,'' and is included in the subsection ``Improving Health and

Quality of Life'' (``http://www.cdc.gov/od/owh/whily.htm'' accessed on

11/26/97). This electronically available information (submitted to the

agency as a hardcopy reprint from the Internet information) is not

dated, is approximately three standard printed pages in length, and

covers the topics of coronary heart disease, cancer, stroke, and other

diseases.

FDA asked CDC whether this statement is an ``authoritative

statement'' under FDAMA. CDC responded that the statement is not an

authoritative statement of CDC because, although it is a statement from

CDC, it is not based upon a deliberative review of the scientific

evidence regarding the nutrient-disease relationship in question;

rather, it is a statement from an educational fact sheet developed by

CDC's Office of Women's Health to convey information to the public

(Ref. 5). Therefore, FDA has concluded that the statement is not an

``authoritative statement'' under section 403(r)(3)(C) of the act

because the statement is not based on a deliberative review of the

scientific evidence.

E. Statement 5

Statement 5 reads: ``[It] is likely that certain antioxidants, such

as vitamins C and E, may destroy the oxygen radicals, retard molecular

damage, and perhaps slow the rate of aging.'' The notification

identified Statement 5 as an ``authoritative statement'' for purposes

of making the claim that is the subject of this rulemaking. The

statement is contained in an undated press release from the National

Institute on Aging at NIH, which was provided on the Internet (``http:/

/www.nih.gov/nia/new/press/agingcau.htm'' accessed on 12/1/97). The

press release (submitted to the agency as a hardcopy reprint from the

Internet) states that it is a synopsis of a recent publication

entitled: ``Aging--Causes and Defenses,'' which had been authored by R.

Martin, D. Danger, and N. Holbrook and published in The Annual Review

of Medicine (44:419,429:1993). The press release indicates that it is

providing a synopsis of the publication but does not clarify if the

authors are associated with, or are staff of, NIH. The Annual Review of

Medicine is published periodically by Annual Reviews, Inc., in Palo

Alto, CA. Editors for each volume serve as reviewers for the various

articles included in the volume and contributors are asked to submit

articles to be considered for publication.

The statement is not ``about the relationship between a nutrient

and a disease or health-related condition'' because aging, the absence

of oxygen radicals, and the presence of molecular damage are not

diseases or health-related conditions. FDA has therefore concluded that

the statement does not address a disease or health-related condition

and therefore, as discussed in section I.A.1 of this document, is not

an ``authoritative statement'' under section 403(r)(3)(C) of the act.

F. Statement 6

Statement 6 reads: ``Antioxidants are thought to help prevent heart

attack, stroke and cancer.'' The notification identified Statement 6 as

an ``authoritative statement'' for purposes of making the claim that is

the subject of this rulemaking. The statement is found in Human

Nutrition (quarterly reports of selected research projects, 4th quarter

1996) issued by the USDA's ARS and provided on the Internet (``http://

www.ars.usda.gov/is/qtr/q496/hn496.htm'' accessed on 12/3/97). Human

Nutrition is a periodic compilation of brief (one paragraph)

descriptions of ongoing research being conducted within the various ARS

facilities. The subject statement (submitted to the agency as a

hardcopy reprint from the Internet) appears in a description of

research entitled: ``Do carotenoids--the bright red, yellow and orange

pigments in fruits and vegetables--warrant a Recommended Dietary

Allowance?'' The paragraph describes the nature and outcome of two ARS

studies and is attributed to Betty J. Burr at the USDA Western Human

Nutrition Research Center in San Francisco. The agency notes that the

last sentence of the paragraph is: ``Further ARS studies will try to

shed more light on whether a specific minimum daily intake of

carotenoids is important for good health.''

The context of the paragraph, as well as the wording of the

statement (i.e., ``are thought''), suggests that the scientific

evidence about the relationship in question is preliminary or

inconclusive.

The agency asked USDA whether the statement is an ``authoritative

statement'' under FDAMA. USDA responded to FDA that the statement is

not an authoritative statement of USDA because it was not based upon a

deliberative review of the scientific evidence regarding a relationship

between the nutrient and the disease in question (Ref. 7). USDA

explained that the ARS quarterly reports describe progress on

individual projects without a deliberative review of all relevant

scientific evidence. Therefore, FDA has concluded that the statement is

not an ``authoritative statement'' under section 403(r)(3)(C) of the

act because it is not based on a deliberative review of the scientific

evidence.

In summary, FDA has concluded that the notification does not

include any authoritative statement published by a scientific body as

required by section 403(r)(3)(C) of the act. Accordingly, the subject

claim relating to the relationship between antioxidant vitamins C and E

and the risk in adults of atherosclerosis, coronary heart disease,

certain cancers, and cataracts is not authorized under section

403(r)(3)(C) of the act and is, therefore, prohibited. The agency notes

that, at any future time, a notification may be submitted to the agency

that bases such a claim or claims on a statement that meets the

requirements of section 403(r)(3)(C) of the act. If there is no

authoritative statement that may serve as a basis for such claims, an

interested person may petition the agency under section 403(r)(4) of

the act and Sec. 101.70 to authorize the health claim or claims by

regulation under section 403(r)(3)(B) of the act.

IV. Issuance of an Interim Final Rule, Immediate Effective Date,

and Opportunity for Public Comment

For the reasons described in this section of this document, FDA is

issuing this rule as an interim final rule, effective immediately, with

an opportunity for public comment. New section 403(r)(7)(B) of the act

(21 U.S.C. 343(r)(7)(B)), added by section 301 of FDAMA, provides that

FDA ``may make proposed regulations issued under [section 403(r)]

effective upon publication pending consideration of public comment and

publication of a final regulation'' if the agency ``determines that

such action is necessary * * * to enable [FDA] to act promptly to ban

or modify a claim'' under section 403(r) of the act. For purposes of

judicial review, ``[s]uch proposed regulations shall be deemed final

agency action.'' The legislative history indicates that the agency

should issue rules under this authority as interim final rules (H.

Conf. Rept. 105-399, at 98 (1997)).

[[Page 34091]]

As described in section III of this document, FDA has determined

that the statements submitted in support of the prospective health

claim do not meet the requirements for authoritative statements in

section 403(r)(3)(C) of the act. FDA has determined that it is

necessary to act promptly to prohibit the claim's use under section

403(r)(3)(C) of the act, and accordingly, is issuing this interim final

rule to ban its use under section 403(r)(3)(C).

FDA invites public comment on this interim final rule. The agency

will consider modifications to this interim final rule based on

comments made during the comment period. Interested persons may, on or

before September 8, 1998, submit to the Dockets Management Branch

(address above) written comments regarding this interim final rule.

Comments must be received by that date. Two copies of any comments are

to be submitted, except that individuals may submit one copy. Comments

are to be identified with the docket number found in brackets in the

heading of this document. Received comments may be seen in the office

above between 9 a.m. and 4 p.m., Monday through Friday.

V. Environmental Impact

The agency has determined under 21 CFR 25.30(k) that this action is

of a type that does not individually or cumulatively have a significant

effect on the human environment. Therefore, neither an environmental

assessment nor an environmental impact statement is required.

VI. Analysis of Economic Impacts

A. Benefit-Cost Analysis

FDA has examined the impacts of this interim final rule under

Executive Order 12866. Executive Order 12866 directs Federal agencies

to assess the costs and benefits of available regulatory alternatives

and, when regulation is necessary, to select regulatory approaches that

maximize net benefits (including potential economic, environmental,

public health and safety, and other advantages; distributive impacts;

and equity). According to Executive Order 12866, a regulatory action is

``significant'' if it meets any one of a number of specified

conditions, including having an annual effect on the economy of $100

million; adversely affecting in a material way a sector of the economy,

competition, or jobs; or if it raises novel legal or policy issues. FDA

finds that this interim final rule is not a significant regulatory

action as defined by Executive Order 12866. In addition, it has been

determined that this interim final rule is not a major rule for the

purpose of congressional review.

If in the future FDA authorizes health claims relating to the

relationship between antioxidant vitamins C and E and the risk in

adults of atherosclerosis, coronary heart disease, certain cancers, and

cataracts after finding that there is significant scientific agreement

about these relationships, the cost to consumers of prohibiting this

claim at this time would be the cost of having kept, in the interim,

information from appearing in food labeling that would ultimately be

shown to be scientifically valid, truthful, and not misleading. At this

time, the benefit to consumers of prohibiting this claim is that a

claim that has not been shown to be scientifically valid will not

appear in food labeling. Accordingly, consumers will be able generally

to have confidence when they read food labeling that any diet-disease

relationship information in that labeling has been shown to be

scientifically valid.

A health claim relating to the relationship between antioxidant

vitamins C and E and the risk in adults of atherosclerosis, coronary

heart disease, certain cancers, and cataracts has not been authorized

under existing regulations. The prohibition of this claim in this

interim final rule results in no regulatory changes for firms, and

therefore no costs to firms are attributable to this interim final

rule.

B. Small Entity Analysis

FDA has examined the impacts of this interim final rule under the

Regulatory Flexibility Act. The Regulatory Flexibility Act (5 U.S.C.

601-612) requires Federal# agencies to consider alternatives that would

minimize the economic impact of their regulations on small businesses

and other small entities. In compliance with the Regulatory Flexibility

Act, FDA finds that this interim final rule will not have a significant

impact on a substantial number of small entities.

A health claim relating to the relationship between antioxidant

vitamins C and E and the risk in adults of atherosclerosis, coronary

heart disease, certain cancers, and cataracts has not been authorized

under existing regulations. The prohibition of this claim in this

interim final rule results in no regulatory changes for firms, and

therefore this rule will not result in a significant increase in costs

to any small entity. Therefore, this rule will not have a significant

economic impact on a substantial number of small entities. Accordingly,

under the Regulatory Flexibility Act (5 U.S.C. 601-612), the agency

certifies that this interim final rule will not have a significant

economic impact on a substantial number of small entities.

C. Unfunded Mandates Reform Act of 1995

FDA has examined the impacts of this interim final rule under the

Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). This

interim final rule does not trigger the requirement for a written

statement under section 202(a) of UMRA because it does not impose a

mandate that results in an expenditure of $100 million or more by

State, local, and tribal governments in the aggregate, or by the

private sector, in any 1 year.

VII. The Paperwork Reduction Act of 1995

This interim final rule contains no collections of information.

Therefore, clearance by the Office of Management and Budget under the

Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520) is not required.

VIII. References

The following references have been placed on display in the Dockets

Management Branch (address above) and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday through Friday.

1. Commission on Dietary Supplement Labels, ``Report of the

Commission on Dietary Supplement Labels,'' November 1997, p. vii.

2. Notification to Donna E. Shalala, DHHS, from Jonathan W.

Emord et al., Emord & Associates, P.C., Counsel for Weider Nutrition

International, Inc., February 23, 1998.

3. ``Food Labeling--Questions and Answers--Volume I--For

Guidance to Facilitate the Process of Developing or Revising Labels

for Foods Other than Dietary Supplements,'' August 1993, Questions

C1-C54.

4. ``Food Labeling--Questions and Answers--Volume II--A Guide

for Restaurants and Other Retail Establishments,'' August 1995,

Questions R117-R127.

5. Letter to Christine J. Lewis, CFSAN, FDA, from Dixie E.

Snider, CDC, April 21, 1998.

6. Letter to Christine Lewis, CFSAN, FDA, from William R.

Harlan, NIH, April 30, 1998.

7. Letter to Christine Lewis, CFSAN, FDA, from Eileen Kennedy,

USDA, May 7, 1998.

Dated: June 16, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98-16454 Filed 6-19-98; 8:45 am]

BILLING CODE 4160-01-F