49868 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

paragraph (d) of this section and shall

state:

This statement has not been evaluated by

the Food and Drug Administration. This

product is not intended to diagnose, treat,

cure, or prevent any disease.

(2) Where there is more than one such

statement on the label or in the labeling,

each statement shall bear the disclaimer

in accordance with paragraph (c)(1) of

this section, or a plural disclaimer may

be placed in accordance with paragraph

(d) of this section and shall state:

These statements have not been evaluated

by the Food and Drug Administration. This

product is not intended to diagnose, treat,

cure, or prevent any disease.

(d) Placement. The disclaimer shall be

placed adjacent to the statement with no

intervening material or linked to the

statement with a symbol (e.g., an

asterisk) at the end of each such

statement that refers to the same symbol

placed adjacent to the disclaimer

specified in paragraphs (c)(1) or (c)(2) of

this section. On product labels and in

labeling (e.g., pamphlets, catalogs), the

disclaimer shall appear on each panel or

page where there such is a statement.

The disclaimer shall be set off in a box

where it is not adjacent to the statement

in question.

(e) Typesize. The disclaimer in

paragraph (c) of this section shall appear

in boldface type in letters of a typesize

no smaller than one-sixteenth inch.

Dated: September 11, 1997.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97–24730 Filed 9–22–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket Nos. 95N–0245, 95N–0282, and

95N–0347]

RIN 0905–AD96

Food Labeling; Nutrient Content

Claims: Definition for ‘‘High Potency’’

and Definition of ‘‘Antioxidant’’ for Use

in Nutrient Content Claims for Dietary

Supplements and Conventional Foods

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending its

regulations to: Define the term ‘‘high

potency’’ as a nutrient content claim;

define nutrient content claims using the

term ‘‘antioxidant’’ (e.g., ‘‘good source

of antioxidants,’’ ‘‘high in antioxidants,’’

‘‘more antioxidants’’); and to correct an

omission pertaining to the use of ‘‘sugar

free’’ claims on dietary supplements.

FDA is taking these actions to provide

for the use of additional nutrient

content claims on labels or in labeling

in accordance with provisions of the

Nutrition Labeling and Education Act of

1990.

EFFECTIVE DATE: March 23, 1999.

FOR FURTHER INFORMATION CONTACT:

Camille E. Brewer, Center for Food

Safety and Applied Nutrition (HFS–

165), Food and Drug Administration,

200 C St. SW., Washington, DC 20204,

202–205–5483.

I. Background

On June 18, 1993 (58 FR 33731), FDA

published a proposal entitled ‘‘Food

Labeling; Requirements for Nutrient

Content Claims for Dietary Supplements

of Vitamins, Minerals, Herbs, and Other

Similar Nutritional Substances’’

(hereinafter referred to as the 1993

nutrient content claims proposal). In

that proposal FDA requested comment

on several terms, including ‘‘high

potency’’ that are often encountered on

labels or in labeling of dietary

supplements and that seem to imply

that the dietary supplement will

contribute to good health (58 FR 33731

at 33748). The agency requested

comment on whether there were

established meanings for these terms,

and, if so, whether they characterized

the level of the nutrients in the food and

thus should be considered to be nutrient

content claims. In 1994, in its final rule

in the nutrient content claims

proceeding (hereinafter referred to as

the 1994 nutrient content claims final

rule), based on the comments that it

received, FDA determined that ‘‘high

potency’’ is a claim that characterizes

the level of a nutrient or nutrients and,

therefore, meets the definition of a

nutrient content claim in § 101.13(b) (21

CFR 101.13(b)) (59 FR 378 at 391,

January 4, 1994).

One comment to the 1993 nutrient

content claims proposal stated that FDA

failed to address whether certain claims

regarding antioxidants were within the

scope of the proposed regulation. In the

1994 nutrient content claims final rule,

the agency stated that while such claims

were not explicitly discussed in the

1993 nutrient content claims proposal,

they also are nutrient content claims (59

FR 378 at 389).

However, given the time constraints

under which FDA prepared the 1994

nutrient content claims final rule, the

agency was not able to adopt a

definition either for ‘‘high potency’’ or

for nutrient content claims for

antioxidants. FDA announced its

intention to review the suggestions for

a definition of ‘‘high potency’’ and

‘‘antioxidant’’ claims and, based on

information received in the comments,

to propose an appropriate definition for

these terms (59 FR 378 at 391). In the

Federal Register of December 28, 1995

(60 FR 67184), the agency published a

proposed rule entitled ‘‘Nutrient

Content Claims: Definition for ‘High

Potency’ Claim for Dietary Supplements

and Definition of ‘Antioxidant’ for Use

in Nutrient Content Claims for Dietary

Supplements and Conventional Foods’’

(hereinafter referred to as the high

potency/antioxidant proposal).

The agency received approximately

70 comments in response to the high

potency/antioxidant proposal. A

number of comments supported the

proposal, while others disagreed with

various aspects of the proposal. A few

comments addressed issues that are

outside the scope of this rulemaking. A

summary of the comments, the agency’s

responses to the comments, and a

discussion of the agency’s conclusions

follow.

II. High Potency

In the high potency/antioxidant

proposal, FDA proposed that the term

‘‘high potency’’ may be used on the

labels or in the labeling of dietary

supplements to describe a nutrient that

is present at 100 percent or more of the

Reference Daily Intake (RDI) for

vitamins and minerals, or of the Daily

Reference Value (DRV) for protein and

dietary fiber, per reference amount

customarily consumed. To describe

multinutrient products as ‘‘high

potency,’’ FDA proposed that at least

two-thirds of the nutrients in a product

must be present at 100 percent of the

RDI for vitamins and minerals or of the

DRV for protein and dietary fiber per

reference amount customarily

consumed.

A. ‘‘High Potency’’ as a Nutrient Content

Claim

1. The majority of the comments

agreed that ‘‘high potency’’ is a nutrient

content claim. These comments stated

that the agency’s definition has a basis

in the labeling practices of the dietary

supplement industry, and that

consumers are already familiar with this

definition. Some comments stated that

the term ‘‘high potency’’ is commonly

understood to describe the level of a

nutrient or nutrients in a product,

particularly on dietary supplements of

vitamins and minerals.

On the other hand, a few comments

stated that ‘‘high potency’’ is not a
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49869

nutrient content claim. One comment

suggested that the agency should limit

the scope of its nutrient content claim

regulation of the term ‘‘high potency’’ to

uses involving dietary supplements

containing nutrients with RDI’s or

DRV’s. The comment noted, however,

that the term ‘‘potency’’ has other

meanings used in conjunction with

products containing dietary ingredients

for which no RDI’s or DRV’s have been

established, and that use of the term on

such products should continue to be

allowed, subject to the general

misbranding provisions of the Federal

Food, Drug, and Cosmetic Act (the act).

Other comments stated that the

agency should withdraw the proposal

because ‘‘potency’’ has an alternative

meaning that FDA did not consider. One

comment stated that for botanicals,

equivalent amounts of the same dietary

ingredient from different plants may

differ in the magnitude of the biological

responses they produce. The comment

stated that, if the term ‘‘potency’’ is

incorrectly used to describe the level of

a dietary ingredient, the proper

definition would not be available for

correct use in a manner that would

provide truthful and accurate

information for consumers. The

comment also maintained that the use of

the term ‘‘potency’’ for botanicals

should be reserved for those cases

where biological assays exist. The

comment stated that there would be no

way of verifying the claim for a dietary

ingredient in the absence of a biological

assay for that dietary ingredient.

One comment requested that the

agency prohibit ‘‘high potency’’ claims

for protein and fiber because the

ingestion of 100 percent of the Daily

Value (DV) for these nutrients in single

servings may lead to deleterious health

effects.

As noted in several of the comments,

the term ‘‘high potency’’ is commonly

used to describe the level of a nutrient

or nutrients, particularly for dietary

supplements of vitamins and minerals

and, therefore, meets the definition in

§ 101.13(b) of a nutrient content claim.

Thus, FDA rejects the suggestion that it

withdraw the proposal to define ‘‘high

potency.’’ FDA acknowledges that there

are other meanings for the term ‘‘high

potency.’’ However, these meanings are

not appropriate for consideration in this

proceeding because they do not describe

the level of a nutrient. For example, for

pharmaceuticals, ‘‘potency’’ is a means

of comparing the relative activities of

drugs in a series (Ref. 1). The comment

that discussed the potency of botanicals

seemed to be ascribing to ‘‘potency’’ a

meaning that is closer to the

pharmaceutical use of the term than to

its use as a nutrient content claim. This

rulemaking is about foods, not

pharmaceuticals.

Before terms like ‘‘potency’’ can be

used to describe the level of dietary

ingredients other than vitamins and

minerals, standards would have to be

developed that provide a basis for

characterizing the level of these

substances. Claims regarding the

potency of constituents other than

vitamins or minerals would be

misleading or false if made without the

benefit of standards that establish the

validity of such claims. The agency

encourages the dietary supplement

industry to participate in developing

such standards.

Moreover, the Commission on Dietary

Supplement Labels (the Commission) is

conducting a study on, and will provide

the agency with a report containing

recommendations for the regulation of

label claims and statements for dietary

supplements. Issues relating to the

‘‘potency’’ of botanicals and other

dietary ingredients may be addressed in

the Commission’s final report.

Therefore, the agency believes that

consideration of the issue of alternate

uses for the term ‘‘potency’’ should be

delayed at least until issuance of a final

report from the Commission.

For dietary supplements of vitamins

and minerals, comments supported the

agency’s tentative view that the term

‘‘high potency’’ unambiguously suggests

that the nutrients are present at a certain

level. However, such support was not as

obvious for ‘‘high potency’’ claims on

products containing protein or fiber.

The agency acknowledges the concern

raised by one of the comments about the

long-term health effects of the ingestion

of 100 percent of the DV for protein or

fiber in single servings. In recognition of

this concern, and because

manufacturers who wish to highlight

the level of protein or fiber in a product

may use other defined terms (e.g., ‘‘good

source,’’ ‘‘high,’’ ‘‘more’’) or amount or

percent statements as described in

§ 101.13(i) (e.g., ‘‘30% of the DV for

protein’’), the agency concludes that it

is appropriate to limit the scope of this

definition to nutrients with RDI’s (i.e.,

vitamins and minerals). Manufacturers

also may use other descriptive terms for

protein and fiber (e.g., terms that

describe the quality of protein or the

solubility of fiber), as long as such

claims are truthful and not misleading.

Accordingly, FDA is modifying

proposed § 101.54(f)(1) (redesignated as

paragraph (f)(1)(i)) and (f)(2) to reflect

that the definition of ‘‘high potency’’ is

limited to vitamins or minerals. This

definition of ‘‘high potency’’ precludes

the use of this nutrient content claim for

protein and fiber.

B. Application to Conventional Foods

2. Several comments from the

conventional food industry opposed the

provision that limited use of the term

‘‘high potency’’ to the labels and

labeling of dietary supplements. These

comments argued that the proposal

would establish an elite nutrient content

claim offering attractive marketing

opportunities available only to dietary

supplements. The comments

maintained that this policy would send

the misleading message that nutrients

obtained from dietary supplements are

an especially efficacious way of

achieving a balanced diet. The

comments also stated that, given current

consumer awareness of nutrition, the

term ‘‘high potency’’ may be appropriate

for conventional foods.

The comments pointed out that there

are several conventional foods that

achieve 100 percent of the DV of a

single nutrient without fortification

(e.g., vitamin C in orange juice, vitamin

A in carrots) as well as a number of

foods that achieve 100 percent DV for

the majority of nutrients through

fortification. The comments stated that

the options for describing 100 percent of

the RDI or DRV are limited (e.g., ‘‘100

percent DV of Vitamin C,’’ ‘‘100 percent

DV of ‘X’ vitamins and minerals’’). One

comment suggested that FDA define

synonyms for ‘‘high potency’’ that

would be more appropriate for

conventional foods (e.g., ‘‘ultra high,’’

‘‘naturally ultra high’’). The comment

suggested that FDA establish an ‘‘extra

high’’ claim for which any food

providing at least 30 percent of the DV

of a nutrient would qualify. The

comment stated that such a claim would

enable such foods as fluid milk to be

labeled as ‘‘extra high’’ in calcium.

Another comment suggested that

‘‘superior source of’’ or ‘‘outstanding

source of’’ may be appropriate

synonyms for ‘‘high potency’’ for

conventional foods (e.g., see 56 FR

60366, November 27, 1991; 58 FR

33715, June 18, 1993; 59 FR 354,

January 4, 1994; and 59 FR 395, January

4, 1994).

FDA does not wish to foster the

notion that dietary supplements are a

superior (or an inferior) source of

nutrients or to promote disparate

marketing opportunities for dietary

supplements and conventional foods.

With regard to labels and labeling, the

agency is committed to supporting as

much parity between conventional

foods and dietary supplements as is

possible consistent with the act (e.g., see

56 FR 60366, November 27, 1991; 58 FR
49870 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

33715, June 18, 1993; and 59 FR 354,

January 4, 1994).

The agency is persuaded that the term

‘‘high potency’’ can be meaningful and

helpful to consumers in constructing

healthy daily diets. If FDA were to

adopt the same definition of ‘‘high

potency’’ for conventional foods as for

dietary supplements, given the

acceptance and understanding of this

term from its use on supplements, there

is little likelihood that consumers

would be confused about the meaning of

the claim were it to appear on

conventional foods. The agency

concludes that the term will likely be

useful in highlighting for consumers

those products (either dietary

supplements or conventional foods) that

contain 100 percent or more of the DV

for specific nutrients in one serving.

Therefore, FDA is not adopting

proposed § 101.13(b)(6), which would

have limited the use of ‘‘high potency’’

to dietary supplements. FDA also is

revising proposed § 101.54(f)(1)

(redesignated as paragraph (f)(1)(i)) and

(f)(2) to remove the restriction that the

term ‘‘high potency’’ be used only on

dietary supplements.

The possibility of foods achieving 100

percent of the DV for certain nutrients

through fortification was raised in one

of the comments. FDA has considered

the appropriateness of fortifying a food

to meet the requirements for bearing the

nutrient content claims in consideration

of the terms ‘‘more’’ (56 FR 60421,

November 27, 1991 and 58 FR 2302,

January 6, 1993) and ‘‘healthy’’ (59 FR

24232, May 10, 1994). The agency stated

that, although random fortification

could lead to deceptive and misleading

claims, fortification of foods in

accordance with the policy set out in

§ 104.20 (21 CFR 104.20) would ensure

that the fortification was rational, and

that the resultant claims would not be

misleading.

FDA has previously stated that

fortifying a food of little or no

nutritional value for the sole purpose of

qualifying that food for a health claim

is misleading for several reasons. First,

there is great potential to confuse

consumers if foods like sugars, soft

drinks, and sweet desserts are fortified

to qualify for a claim, when, at the same

time, dietary guidance as contained in

the U.S. Department of Agriculture’s

(USDA’s) and U.S. Department of Health

and Human Services’ (DHHS’) 1995

Dietary Guideline for Americans, for

example, states that these foods provide

calories and little else nutritionally (Ref.

2). Indiscriminate fortification of such

foods with one nutrient would not make

such foods consistent with dietary

guidelines and may encourage

overfortification of the food supply (e.g.,

vitamin or mineral addition to soft

drinks). Consistent with the provisions

for ‘‘more’’ and ‘‘healthy’’ claims, the

agency concludes that adherence to the

principles stated in its fortification

policy in § 104.20 will ensure that a

food is not indiscriminately fortified for

the sole purpose of making a ‘‘high

potency’’ claim. Accordingly, the

agency is adding new § 101.54(f)(3)

which states that, where compliance

with the definition of ‘‘high potency’’ is

based on a nutrient that has been added

to the food (other than a dietary

supplement), fortification shall be in

accordance with the policy on

fortification of foods in § 104.20.

The agency points out that it is in the

process of reviewing its policy on

fortification for the purpose of making

health claims. Currently, no expressed

or implied health claims may be made

on the label or in labeling for a food

unless the food contains 10 percent or

more of the RDI or DRV for vitamin A,

vitamin C, iron, calcium, protein, or

fiber per reference amount customarily

consumed before any nutrient addition

(see § 101.14(e)(6) (21 CFR 101.14(e)(6)).

In response to petitions from the

National Food Processors Association

and the American Bakers Associations,

FDA proposed modifications to

§ 101.14(e)(6) to allow fruit and

vegetable products comprised solely of

fruits and vegetables, enriched grain

products that conform to a standard of

identity, and certain other products that

do not contain 10 percent of one of the

six listed nutrients, to bear health

claims if they meet all other

requirements for the claim. FDA is

reviewing comments on this proposal

(60 FR 66206, December 21, 1995).

With regard to synonyms for nutrient

content claims, the agency has stated

(58 FR 2302 at 2320):

Because a goal of the 1990 amendments is

to make nutrition information on the label or

labeling of foods available in a form that

consumers can use to follow dietary

guidelines (H. Rept. 101–538, supra, 10), and

the act envisions that synonyms for defined

terms can be an appropriate means to

communicate such information, the agency

will evaluate synonyms according to the

standard in the 1990 amendments, i.e., that

the term is commonly understood to have the

same meaning as a defined term. In doing so,

FDA intends to be open to considering terms

that meet this standard. However, FDA does

not intend to permit any synonym that it

believes would be unclear in meaning to

consumers with respect to characterizing the

level of a nutrient in a food.

The agency has no evidence that

terms such as ‘‘superior source of’’ or

‘‘outstanding source of’’ are commonly

understood to have the same meaning as

‘‘high potency.’’ Likewise, FDA is not

aware of any basis on which it could

find that terms such as ‘‘very,’’ ‘‘ultra,’’

or ‘‘extra’’ would be understood by

consumers to be synonymous with

‘‘high potency.’’ Furthermore, terms

such as ‘‘ultra’’ do not signify the

quantity present and therefore may not

provide meaningful information to the

consumer. Therefore, FDA is not

authorizing these terms for use as

synonyms to the ‘‘high potency’’

nutrient content claim. Interested

parties may petition the agency to

authorize synonyms or new nutrient

content claims under the procedures

described in § 101.69 (21 CFR 101.69).

The agency also points out that, on

October 25, 1994, the National Food

Processors Association (NFPA)

petitioned FDA to initiate rulemaking

for the adoption of amendments to the

regulations governing nutrient content

claims and health claims. Among other

things, the petition requested that the

agency allow manufacturers to tie or

‘‘anchor’’ an undefined term (e.g.,

‘‘loads of’’) to a defined nutrient content

claim (e.g., ‘‘high’’) as a synonym for

that defined term, without FDA

preclearance of the undefined term,

when the terms are understood by

consumers to have the same meaning,

when such claims are made in

accordance with the requirements for

the defined term, and when the defined

term also appears in the product’s

labeling. The proposal responding to the

NFPA petition published on December

21, 1995 (60 FR 66206). FDA is

currently evaluating comments to that

proposal.

C. 100 Percent Criterion

3. Many comments supported the

proposal to define ‘‘high potency’’ as

100 percent of the DV.

One comment from a trade association

for dietary supplement manufacturers

objected to the basis for selecting 100

percent of the DV as the requirement for

high potency. The association argued

that 100 percent is not sufficient to meet

the needs of practically all healthy

persons, at least for some nutrients, and

that this amount is not necessarily the

amount that some consumers require to

meet what they consider optimal targets

for nutrient intake.

One comment stated that consumers

will understand ‘‘full potency’’ to equal

100 percent of the DV, but that the term

‘‘high potency’’ conveys the impression

that the nutrient content is above 100

percent. The comment stated that to

avoid confusion and protect consumers

from misleading information, FDA

should not adopt a definition for ‘‘high

potency’’ until it has conducted a
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49871

survey of consumers of dietary

supplements concerning public

understanding of the meaning of the

terms ‘‘high potency’’ and ‘‘full

potency.’’ The comment recommended

that FDA adopt not one but two nutrient

content claims, one for ‘‘full potency’’

and another for ‘‘high potency.’’ Other

comments stated that ‘‘full potency’’ is

not an appropriate synonym for ‘‘high

potency’’ but offered no explanation.

A couple of comments suggested that

the proposed regulations be revised to

define ‘‘high potency’’ for the B

vitamins as well as vitamins C and E as

above 100 percent of their respective

DV’s to be consistent with current

marketing practices that typically

package these nutrients in amounts well

above 100 percent of the DV for each

nutrient.

The agency rejects the comment that

objected to the basis for the definition

of ‘‘high potency.’’ The RDI’s are based

on the National Academy of Sciences’

Recommended Dietary Allowances

(NAS RDA’s) and are the cornerstone for

several nutrient content claims. Since

the inception of the nutrition labeling

program (37 FR 6493, March 30, 1972),

FDA has relied on the judgment of the

NAS’ Food and Nutrition Board

concerning the essentiality of particular

nutrients in human nutrition and for

recommendations regarding the

required levels of those nutrients to

meet the needs of practically all healthy

persons. The NAS’ RDA’s remain the

most widely accepted and respected

source of information on human

nutrient requirements.

The NAS is in the process of revising

the basis for the RDA’s and may

consider optimal nutrition and the

prevention of chronic disease in

developing a future edition of the RDA’s

(Ref. 3). FDA expects that label

reference values and nutrient content

claims will evolve in tandem with the

RDA’s. In the interim, the agency

concludes that the RDA’s, and the

principles on which they are based,

form a firm foundation on which to

establish certain label reference values

and their derivatives, the nutrient

content claims.

FDA did not propose a definition for

‘‘full potency.’’ In the high potency/

antioxidant proposal, FDA requested

comment on whether the term ‘‘full

potency’’ is generally viewed by

consumers as a synonym to ‘‘high

potency’’ (60 FR 67184 at 67189). The

agency is not persuaded by the

comment that suggested that consumers

interpret ‘‘full potency’’ to mean 100

percent of the DV and ‘‘high potency’’

to mean more than 100 percent because

the comment did not supply any

support for its assertions. In fact, FDA

did not receive comments supporting

‘‘full potency’’ as a synonym for ‘‘high

potency.’’ Therefore, the agency is not

defining ‘‘full potency’’ as a synonym

for ‘‘high potency.’’

FDA does not consider that it is

necessary to adopt a separate definition

for ‘‘full potency’’ because of the lack of

evidence that this term describes the

level of a nutrient, and that it should be

considered a nutrient content claim.

Further, the agency is not persuaded

that consumer research is necessary to

define ‘‘high potency’’ at 100 percent of

the RDI given that most of the comments

supported this definition.

The agency sees no reason to alter the

definition of ‘‘high potency’’ to require

higher levels of certain nutrients

because the definition of ‘‘high

potency’’ does not preclude

manufacturers of the B vitamins,

vitamin C, or vitamin E from marketing

these vitamins at levels above 100

percent of the RDI. The comment did

not include an alternate

recommendation for a definition, nor

did it include any data in support of its

assertion regarding the current levels of

the B vitamins or vitamins C and E

marketed in dietary supplements.

D. Multinutrient Products

4. The majority of comments

supported the criterion that two-thirds

of the nutrients present in a

multinutrient product must be present

at 100 percent of the DV to bear a ‘‘high

potency’’ claim.

One comment stated that FDA’s tally

of the nutrients likely to be present at

levels less than 100 percent of the DV

is incomplete, and, therefore, the

requirement that 2/3 of the nutrients be

present at 100 percent of the RDI may

be more rigid than was actually

intended. The comment stated that

biotin is an extremely expensive

ingredient and is seldom included at

100 percent of the RDI. The comment

maintained that some trace minerals are

commonly present at less than 100

percent of the RDI, and that the

definition of ‘‘high potency’’ should not

require uniformly high levels of these

nutrients. The comment stated that

some products intended for men or for

the elderly now provide less than the

RDI levels of iron which represents a

desirable trend. The comment stated

that requiring that one-half of the

nutrients be present at 100 percent of

the RDI is more appropriate than

requiring that two-thirds be present at

100 percent to bear the ‘‘high potency’’

claim.

One comment suggested that the term

‘‘high potency’’ be used on the label or

in the labeling of a dietary supplement

to describe the product if all of the

nutrients with RDI’s or DRV’s in the

product are at 100 percent or more, with

the exception of: (a) The 11 nutrients

deemed impractical or imprudent in the

high potency/antioxidant proposal to

include at 100 percent of RDI or DRV

levels; and (b) the essential nutrient

iron, because daily supplementation at

100 percent of the RDI level is not

deemed prudent for all people.

One comment recommended that

FDA permit multinutrient products that

contain one or more nutrients to use the

term ‘‘high potency’’ along with a

specific nutrient referenced in the

nutrient content claim. As an example,

the comment suggested that if the

multinutrient product contains 100

percent of the RDI for vitamin C, the

product should be allowed to bear the

claim ‘‘high potency vitamin C.’’ The

comment also suggested that if the

multinutrient product contains 50

percent or more nutrients that are above

RDI levels, the product should be

allowed to declare ‘‘high potency’’ with

an asterisk. The comment stated that the

asterisk would correspond with a same

panel reference that lists the nutrients

with RDI’s or DRV’s at 100 percent of

their label reference values.

Alternatively, the comment suggested

that a company could use a phrase such

as ‘‘See Supplement Facts Panel for a

complete listing, 7 of 12 nutrients in

this product exceed RDI/DRV levels’’ to

draw attention to the number of

nutrients present at 100 percent of the

RDI or DRV.

The agency points out that the

number of nutrients eligible to bear a

‘‘high potency’’ nutrient content claim

has changed from what was proposed

because the claim is now limited to the

vitamin or mineral content of the food

product. However, two-thirds is a

reasonable proportion of nutrients that

should be present for a multinutrient

product to bear the ‘‘high potency’’

claim. To be able to characterize a

dietary supplement or conventional

food as ‘‘high potency,’’ that claim

ought to reflect the nature of the food.

For a product to bear this claim, it is

reasonable to expect that significantly

more than half of the RDI nutrients in

the food meet the ‘‘high potency’’

standard. The two-thirds requirement

appropriately captures this expectation.

Hence, FDA rejects the suggestion that

only 50 percent of the nutrients in a

multinutrient product be present at the

requisite level to qualify for a ‘‘high

potency’’ claim.

FDA concludes that the provision that

two-thirds of the nutrients be present at

100 percent of the RDI for a
49872 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

multinutrient product to bear the term

‘‘high potency’’is sufficiently flexible to

account for the presence at less than 100

percent of the DV for iron, biotin, and

those trace minerals that are typically

not found at 100 percent of the DV.

Because this final rule revises the

proposed definition of ‘‘high potency’’

to include conventional foods, FDA has

revised § 101.54(f)(2) to refer to all

multinutrient products, not just dietary

supplements.

There is nothing in the high potency/

antioxidant proposal that precludes use

of such terms as ‘‘high potency vitamin

C’’ or the use of asterisks that refer to

a listing of nutrients that are present at

100 or more percent of the RDI, either

for a single or a multinutrient product.

To emphasize the fact that the vitamins

or minerals present at 100 percent or

more of the DV can be described by the

term ‘‘high potency,’’ FDA is revising

proposed § 101.54(f)(1) (redesignated as

paragraph (f)(1)(i)) to state that the term

‘‘high potency’’ can be used to describe

individual vitamins or minerals that are

present at 100 percent or more of the

RDI. However, if the term ‘‘high

potency’’ is used on the label of a

multinutrient product to refer to the

entire product, the two-thirds criterion

must be met. There is nothing in

§ 101.54(f) that precludes other

descriptive statements (e.g., ‘‘7 of 12

nutrients in this product exceed RDI/

DRV levels’’) as long as they are truthful

and not misleading.

FDA recognizes that there are

‘‘combination’’ products that contain, in

addition to vitamins and minerals,

dietary ingredients for which no label

reference value has been established

(e.g., botanicals). (See comment 1 of this

document.) FDA advises that the label

or labeling of such products must

clearly identify which dietary

ingredients are being described by the

term ‘‘high potency’’ (e.g., ‘‘botanical ’X’

with high potency vitamin D’’), so that

FDA can evaluate the appropriateness of

the claim under the definition for high

potency in § 101.54. Where there is any

ambiguity regarding the use of the term

‘‘high potency,’’ the agency will

evaluate the claim on a case-by-case

basis in the context of the entire label

and labeling to determine whether the

claim is being used to describe the level

of a nutrient or to describe the product.

Accordingly, FDA is adding new

§ 101.54(f)(1)(ii) to state that products

that contain vitamins or minerals as

well as other nutrients or dietary

ingredients shall clearly identify which

ingredients are described by the term

‘‘high potency.’’

5. A couple of comments stated that

it is possible that some substances that

are technically vitamins and minerals

are present in multingredient products

at less than 2 percent of the DV (and

hence are excluded from nutrition

labeling) but perform technological

functions in the finished supplement.

The comments suggested that these

ingredients should not be part of the

denominator in determining whether a

product meets the two-thirds criterion

for a ‘‘high potency’’ claim. The

comment recommended that proposed

§ 101.54(f)(2) be revised to clarify that

vitamins or minerals present at less than

2 percent of the DV are excluded from

being counted with the one-third of the

nutrients that may be present to qualify

for the claim.

FDA agrees that nutrients present in

insignificant amounts should be

excluded from being counted in the

denominator for determining the ratio of

nutrients present at 100 percent of the

RDI as long as they are used for

technological purposes only and are

declared only in the ingredient

statement. These same criteria are used

in § 101.9(c)(8)(ii)(B) (21 CFR

101.9(c)(8)(ii)(B)) to define vitamins and

minerals that may be omitted from

nutrition labeling. For vitamins and

minerals in conventional foods and

dietary supplements, the agency defines

any amount less than 2 percent of the

RDI as insignificant (see

§ 101.9(c)(8)(iii)). Accordingly, the

agency is revising proposed

§ 101.54(f)(2) to state that the term ‘‘high

potency’’ may be used on the label or in

the labeling of a food product to

describe the product if it contains 100

percent or more of the RDI for at least

two-thirds of the vitamins and minerals

that are listed in § 101.9(c)(8)(iv) and

that are present in the product at 2

percent or more of the RDI (e.g., ‘‘High

potency multivitamin, multimineral

dietary supplement tablets’’).

III. Antioxidants

In the high potency/antioxidant

proposal, FDA proposed that the term

‘‘antioxidant’’ be defined as a collective

term inclusive of vitamin C, vitamin E,

and beta-carotene when used as part of

a nutrient content claim (e.g., ‘‘good

source of antioxidants’’). The agency

proposed that the levels of these

nutrients must be sufficient to qualify

for a nutrient content claim that

characterizes the level of antioxidants in

a food without further specifying the

antioxidant nutrient. For example, to

qualify for a ‘‘high in antioxidants’’

claim, FDA proposed that the product

must contain 20 percent or more of the

RDI for vitamin C and for vitamin E per

reference amount customarily

consumed, and that 20 percent or more

of the RDI for vitamin A must be present

as beta-carotene per reference amount

customarily consumed. The agency

proposed that if the food does not

contain all three antioxidants at the

requisite level, the claim must specify

which antioxidants in the food meet the

required level (e.g., ‘‘high in antioxidant

vitamins C and E’’). FDA proposed that

nutrient content claims for antioxidants

be authorized for both conventional

foods and dietary supplements. Finally,

the agency proposed that a collective

term (e.g., ‘‘complete antioxidant

complex,’’ ‘‘antioxidant complex’’) may

be used on the labels or in labeling

provided that vitamin C and vitamin E

are present at 10 percent or more of the

RDI per reference amount customarily

consumed, and that 10 percent or more

of the RDI for vitamin A is present as

beta-carotene per reference amount

customarily consumed.

A. Underlying Concepts

6. A few comments requested that the

agency withdraw the proposal. One

comment stated that the proposal did

not discuss the characteristics of

botanicals or other nonnutrients that act

as antioxidants in the human body.

Another comment suggested that the

agency broaden its definition to

encompass all vitamins, minerals, and

plant compounds involved in

antioxidant processes. This comment

suggested that FDA rely on the 20

percent criterion (i.e., 20 percent or

more of the DV, the definition for

‘‘high’’ claims) for those nutrients with

RDI’s but permit the use of the content

claim using the term ‘‘antioxidants’’

with an asterisk for all other such

substances when present in any

cognizable amount in food. For

example, the comment suggested that

the asterisk correspond with the same

panel reference to the following

statement: ‘‘This product

contains—————, an antioxidant. An

RDI reference amount has not been

established for this nutrient.’’ One

comment stated that only RDI nutrients

should be permitted to claim ‘‘high in

antioxidants’’ or ‘‘good source of

antioxidants’’ but argued that terms

such as ‘‘contains’’ or ‘‘provides

antioxidants’’ should be available for

use with other proven antioxidants.

The agency rejects the suggestion that

the antioxidant proposal be withdrawn.

The purpose of this rulemaking is to

define a term used in nutrient content

claims that characterize the level in

foods of certain antioxidant nutrients.

Without such a definition, claims on the

label or in labeling of food that describe

the level of ‘‘antioxidants’’ would,

under section 403(r)(1)(A) of the act (21
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49873

U.S.C. 343(r)(1)(A)), misbrand the

products on which they appear.

Under section 403(r)(1)(A) of the act,

a claim that characterizes the level of

any nutrient which is of the type

required by section 403(q)(1) or (q)(2) to

be listed in nutrition labeling may not

be made unless the claim is made in

accordance with a regulation that FDA

adopts under section 403(r)(2) to define

the claim. This rulemaking is intended

to define the circumstances in which

claims can be made that characterize the

level of ‘‘antioxidant’’ substances in

food. Unless FDA completes this

rulemaking, labels of dietary

supplements, as well as of other foods,

cannot contain statements that

characterize the levels of

‘‘antioxidants.’’

The agency is not persuaded that the

term ‘‘antioxidants,’’ when used in

defined nutrient content claims, should

be broadened to include all substances

involved in antioxidant processes. The

purpose of this rulemaking is not to

delineate all known antioxidants. The

comments that stated that there are

other dietary ingredients that act as

antioxidants reflect a misinterpretation

of FDA’s intent. FDA is not restricting

all label and labeling statements about

antioxidants to statements about only a

limited number of nutrients. Rather, the

agency is defining the circumstances in

which claims that characterize the level

of nutrients that have antioxidant

activity, such as ‘‘high in antioxidants’’

can be made in compliance with the

requirements of the act. As stated above,

manufacturers cannot make label

statements that characterize the level of

a nutrient unless FDA has defined such

statements by regulation (see section

403(r)(1)(A) of the act), and FDA cannot

define such statements unless it has a

reference point, that is an RDI or DRV,

against which to measure the nutrient

levels. Many of the plant compounds

referred to in the comments as

antioxidants (e.g., lycopene, lutein,

polyphenols) do not have RDI’s, and

thus it is not possible to characterize the

level of these substances because there

is no standard against which to do so.

Consequently, they cannot be the

subject of nutrient content claims at this

time. However, FDA did not intend in

this rulemaking to decide whether these

substances have, or do not have,

antioxidant activity.

The agency is not limiting truthful

and nonmisleading statements about the

properties or the effects of antioxidants.

Manufacturers may, for example, craft a

statement, subject to section 403(a) of

the act, that describes how a nutrient or

dietary ingredient that does not have an

RDI participates in antioxidant

processes. Likewise, claims that

describe the effect of a nutrient or

dietary ingredient on the structure or

function of the body may be made as

long as such claims are not false or

misleading and, if appropriate, are made

in accordance with section 403(r)(6) of

the act (see comment 8 of this

document). However, irrespective of

how many antioxidant substances there

are, claims characterizing levels of

nutrients or dietary ingredients are not

permitted unless authorized by a

regulation.

To address the misinterpretation of

the agency’s intentions, that is evident

in the comments, and to clarify the

scope of this rulemaking, FDA is

changing the paragraph heading in

§ 101.54(g) from ‘‘Antioxidant claims’’

to ‘‘Nutrient Content Claims Using the

Term ’Antioxidant’.’’ In addition, to

emphasize that this regulation concerns

the level of certain nutrients, FDA is

inserting new text in § 101.54(g) that

states that nutrient content claims that

characterize the level of one or more

antioxidant nutrients present in a food

may be used on the label or in the

labeling of that food when the nutrients

meet the conditions that are established

in this regulation. Among the conditions

set out in § 101.54(g)(1) is the

requirement that an RDI must have been

established for each nutrient that is to

be subject of a claim.

Regarding the comment that argued

that terms such as ‘‘contains’’ or

‘‘provides’’ antioxidants be available for

use with antioxidants without

established RDI’s, the agency points out

that ‘‘contains’’ and ‘‘provides’’ are

synonyms for the defined nutrient

content claim ‘‘good source’’ (see

§ 101.54(c)) and, thus, under section

403(r)(1)(A) of the act, can only be used

with nutrients for which RDI’s have

been established. Consequently, a claim

such as ‘‘contains lycopene’’ would be

an unauthorized nutrient content claim

because lycopene does not have an RDI.

Nonetheless, a statement such as ‘‘‘x’ mg

of lycopene per serving’’ is permitted

under § 101.13(i)(3), which allows for

the use of amount or percentage

statements that do not implicitly

characterize the level of the nutrient in

a food (e.g., claims that do not imply

whether the amount is high or low

based on an established RDI or DRV

value), so long as the statement is not

misleading in any way. (See Ref. 4, p.

36, C23). For dietary supplements,

certain other statements (i.e., simple and

comparative percentage claims) can be

made under new § 101.13(q)(3)(ii) (see

the document entitled ‘‘Food Labeling;

Requirements for Nutrient Content

Claims, Health Claims, and Statements

of Nutritional Support for Dietary

Supplements’’ (hereinafter referred to as

‘‘the nutrient content claims

document’’) published elsewhere in this

issue of the Federal Register for further

discussion of this issue). Further, as

discussed fully under comment 8 of this

document, other statements about

antioxidant properties of food

substances may appear on the labels of

foods, provided that they are made in

accordance with the statutory

requirements.

7. One comment stated that the

proposal lacked a scientific definition of

the term ‘‘antioxidant’’ and suggested

that the agency repropose and include a

definition for this term. Other comments

stated that the distinction between

direct and indirect antioxidants made

by the agency in the proposal was not

useful. These comments argued that

consumers are unlikely to distinguish

between direct and indirect

antioxidants, and that research shows

that minerals such as copper,

magnesium, zinc, and selenium have

known antioxidant effects. The

comments asserted that these nutrients

should be grouped with vitamin C,

vitamin E, and beta-carotene for the

purpose of making nutrient content

claims about antioxidants.

One comment stated that the

endorsement of vitamin C, vitamin E,

and beta-carotene could send a

misleading message to consumers that

these nutrients will prevent disease, that

scientists have reached a consensus on

the mechanisms underlying disease

prevention, and that the consumption of

a few common antioxidants in and of

itself provides health benefits. The

comment stated that, as a result,

consumers may be tempted to take

supplements of individual antioxidants,

which may have deleterious health

consequences or at least no significant

benefits.

One comment requested that FDA

establish criteria for determining the

biological endpoints to be achieved by

the use of antioxidants. The comment

also suggested that FDA establish a

definition for the total antioxidant

activity of whole foods.

In the high potency/antioxidant

proposal and in an earlier rulemaking

(56 FR 60624, November 27, 1991), the

agency summarized the antioxidant

properties of vitamin C, vitamin E, and

beta-carotene. The agency stated that

there was scientific evidence that these

nutrient substances were able to trap

and deactivate reactive oxygen

molecules and, thus, prevent the

damage caused by these reactive

molecules (also called free radicals).
49874 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

No evidence was presented in the

comments that nutrient content claims

for vitamin C, vitamin E, and betacarotene will be construed by

consumers to be an endorsement that

the nutrients that are the subject of such

claims will prevent disease or, by

themselves (that is, in the absence of a

healthy total daily diet), provide

inordinate health benefits. Therefore,

there is no basis for the agency not to

confirm its proposal that these nutrients

can be subjects of nutrient content

claims for antioxidants.

In the high potency/antioxidant

proposal, the agency tentatively

concluded that only vitamin C, vitamin

E, and beta-carotene possessed direct

antioxidant activity. The agency

tentatively concluded that nutrients

such as zinc, manganese, copper,

selenium, riboflavin, and niacin should

not be classed as antioxidants for the

purpose of making nutrient content

claims (60 FR 67184). This tentative

conclusion was based on the fact that

these nutrients are precursors of

coenzymes that are involved in

oxidative reactions but do not have

direct antioxidant activities, and that

they may have effects that are both

antioxidant and pro-oxidative in

character.

FDA acknowledges that there is new

literature on antioxidants, some of

which calls into question the relevance

of the distinction between direct and

indirect antioxidants (e.g., see Refs. 5

through 15). Based on the comments

and a review of this literature (e.g., see

Refs. 5 through 15), FDA is persuaded

that it is reasonable to allow all

nutrients that have antioxidant activity

or that participate in antioxidant

reactions to be the subject of nutrient

content claims for antioxidants, so long,

of course, as an RDI has been

established for the nutrient. Based on

the state of the science, FDA is not able

to justify establishing a more limited list

of nutrients.

However, FDA is not specifying the

nutrients that may be the subject of the

claim in the codified language of

§ 101.54 because some nutrients with

reported antioxidant activity (e.g.,

copper, manganese, iron) are prooxidative at certain levels (60 FR

67184). A manufacturer making an

antioxidant claim for a nutrient must

have substantiation that the nutrient

functions as an antioxidant at the levels

present and under the intended

conditions of use. The agency advises

that antioxidant claims on products that

contain levels of a nutrient sufficient to

cause the nutrient to act as a prooxidant are false and misleading under

section 403(a) of the act.

Based on its conclusion that nutrients

that exhibit antioxidant activity through

an indirect mechanism in fact have an

antioxidant function when present at

certain levels, and that manufacturers

should be able to inform consumers

about their presence, FDA is broadening

the number of nutrients that can be the

subject of a nutrient content claim that

characterizes the level of antioxidants.

Accordingly, the agency is revising

proposed § 101.54(g)(1) and (g)(2) to

delete the language that would have

limited the nutrients that could be the

subject of antioxidant content claims to

vitamin C, vitamin E, and beta-carotene

and to include in its stead general

language that refers to nutrients that

have recognized antioxidant activity.

The agency is defining the conditions

for the use of the term ‘‘antioxidant’’ in

nutrient content claims in § 101.54(g).

This section provides that the term

antioxidant may be used for a substance

for which there is scientific evidence

that, following absorption from the

gastrointestinal tract, the substance

participates in physiological,

biochemical, or cellular processes that

inactivate free radicals or that prevent

free radical-initiated chemical reactions.

This definition captures the attributes of

those nutrients that the agency has

previously concluded are direct

antioxidants (i.e., vitamin E, vitamin C,

and beta-carotene) (56 FR 60624 and 60

FR 67184), as well as the attributes of

those nutrients that the agency has

described as indirect antioxidants (60

FR 67184).

While the agency believes that this

definition for antioxidant, which

responds to comments and which is

based on available scientific

discussions, is the most appropriate

definition at this time, it is clear that a

widely accepted and well-established

definition for antioxidants has not been

developed within the scientific

community. In the near future, the NAS

Institute of Medicine (IOM) will be

conducting a comprehensive assessment

of human nutrient requirements for

dietary antioxidants. This review will

consider both the nature of the

definition of a dietary antioxidant as

well as the linkage between dietary

reference intakes and antioxidant

activity. FDA expects to carefully

review the outcomes and final report of

the IOM to the extent that they are

relevant to this final rulemaking. The

agency may consider reexamining its

conclusions on nutrient content claims

for antioxidants based on discussions

provided in the IOM report when it

becomes available. The agency will

consider proposing an affirmative list of

antioxidant nutrients and limiting

nutrient content claims to such a list

following the release of the IOM report.

The agency is revising proposed

§ 101.54(g)(3) to specify the levels of

nutrients needed to qualify for

antioxidant nutrient content claims.

Section 101.54(g)(3) states that the level

of each nutrient that is the subject of the

claim must be sufficient to qualify for

the claim (e.g., to bear the claim ‘‘high

in antioxidant vitamin C,’’ the product

must contain 20 percent or more of the

RDI for vitamin C). Beta-carotene may

be a subject of the claim when the level

of vitamin A present as beta-carotene in

the food that bears the claim is

sufficient to qualify for the claim. For

example, to bear the claim ‘‘good source

of antioxidant beta-carotene,’’ 10

percent or more of the RDI for vitamin

A must be present in the food as betacarotene per reference amount

customarily consumed. When a product

contains more than one antioxidant

nutrient, each antioxidant nutrient that

is being described must meet the level

of nutrient specified in the nutrient

content.

It is important that the antioxidant

nutrients be identified as part of a

nutrient content claim for antioxidants

because the names are facts that are

material in light of the antioxidant

representation. The comments reveal

that a variety of nutrients and dietary

ingredients could be considered

antioxidants. Since these final rules

allow the manufacturer to determine

what nutrients in a product meet the

definition in § 101.54(g) for antioxidants

and are to be the subject of the nutrient

content claim, the claim would be

confusing to consumers without a clear

identification of which nutrients in the

product are being described. Consumers

cannot be expected to know which

nutrients are antioxidants. There are no

regulatory provisions for providing this

information in the nutrition label, and it

will not necessarily be revealed in the

ingredient statement. In addition, some

products may contain several

antioxidants, with only a few of them

being present at levels appropriate for

the claim. In this case, the claim clearly

needs to identify which nutrients meet

the criteria for the claim being made.

The agency concludes that without

the disclosure of the nutrients

proximate to the claim, a claim on the

label or in labeling of food that

describes the level of antioxidants

would be misleading under section

201(n) of the act. Accordingly, FDA is

adding new § 101.54(g)(4) that states

that the names of the nutrients that are

the subject of the claim must be

included as part of the claim (e.g., ‘‘high

in antioxidant vitamins C and E’’).
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49875

For flexibility, the agency concludes

that the names of the nutrients may be

included as part of the claim either

directly, by mentioning them in the

claim, or indirectly, by use of an

asterisk. Because the claim may refer to

many nutrients, and space constrains

may make it difficult to fit the entire list

within the claim, FDA is willing to

provide the same flexibility in how

antioxidant claims are made that it is

allowing for the disclaimer required

with statements made under section

403(r)(6) of the act. (For further

discussion of the placement of the

disclaimer, see the nutrient content

claims document published elsewhere

in this issue of the Federal Register.) As

with the disclaimer, the agency

concludes that the list of nutrients

should be on the same panel or page as

the claim. This placement establishes an

obvious relationship between the claim

and the list of antioxidant nutrients. The

placement of the list of nutrients on

another panel would obscure material

facts necessary for understanding the

claim.

With respect to type-size

requirements, section 403(r)(2)(A)(iii)

through (r)(2)(A)(v) of the act requires

that statements that disclose the level of

fat, saturated fat, or cholesterol, which

must be presented in conjunction with

certain nutrient content claims, ‘‘have

appropriate prominence which shall be

no less than one-half the size of the

claim.’’ The agency concludes that, for

consistency in identifying material

information, the standard embodied in

these provisions should be applied to

the disclosure of the antioxidant

nutrients.

The agency recognizes that sometimes

claims may be small, particularly in

labeling, and one-half the type size of

the claim may result in a type size that

is too small to be easily read. Thus,

there is a need for a minimum type size

for the list of antioxidant nutrients. Onesixteenth of an inch is specified in

§ 101.2(c) (21 CFR 101.2(c)) as the

minimum type size for most mandatory

information on the principal display

panel or information panel, e.g.,

designation of ingredients, name and

place of business, and warning and

disclaimer statements. Further, onesixteenth of an inch is the minimum

size required in § 101.105(i) for net

quantity of contents statements.

Consequently, the agency concludes

that a minimum type size of onesixteenth of an inch for the disclosure

of the antioxidant nutrients is necessary

to ensure that it is prominently

displayed. However, for the sake of

increased prominence, it is preferable to

use one-half the size of the claim when

it results in a type size of larger than

one-sixteenth of an inch.

Accordingly, FDA is adding new

§ 101.54(g)(4) which permits the term

‘‘antioxidant’’ or ‘‘antioxidants’’ (as in

‘‘high in antioxidants’’) to be linked by

a symbol (e.g., an asterisk) that refers to

the same symbol that appears elsewhere

on the same panel of the product label

followed by the name or names of the

nutrients with recognized antioxidant

activity. The list of nutrients must

appear in letters of type size of no

smaller than the larger of one-half of the

type size of the largest nutrient content

claim or 1/16 inch.

The issue of biological endpoints,

raised by one of the comments, is

beyond the scope of this rulemaking. It

was not clear whether the comment that

requested that FDA establish criteria for

biological endpoints to be achieved by

the use of antioxidants was asking FDA

to establish a standard biological

measurement (or biomarker) to

determine whether a substance has

antioxidant activity in vivo, or asking

FDA to set forth criteria for establishing

when the use of antioxidants provides

protection from disease. In either case,

such issues are outside the scope of

what FDA proposed to do in this

rulemaking.

The same comment also suggested

that FDA establish a definition for the

total antioxidant activity of whole foods.

FDA recognizes that foods may contain

a mixture of substances, both nutrients

and nonnutrients, that participate in

antioxidant processes. However, there

are no reliable methods available that

measure the antioxidant activity of all

substances that participate in

antioxidant reactions when an entire

food is consumed. The development of

a definition of total antioxidant activity

of whole foods is beyond the scope of

this regulation, which is intended to

permit the use of the term

‘‘antioxidants’’ in claims that

characterize the level of these nutrients

in a food, including a dietary

supplement.

8. A couple of comments stated that

the term ‘‘antioxidant’’ is a statement

provided for under section 403(r)(6) of

the act. These comments requested

clarification on whether the use of the

term ‘‘antioxidant’’ is part of a statement

about a product’s biological function.

The comments stated that factual

statements about the biological function

of antioxidants should be permitted,

provided that the labeling does not

include unauthorized health or nutrient

content claims.

Another comment stated that FDA

lacks authority to define the term

‘‘antioxidant’’ for use in nutrient

content claims under section

403(r)(2)(A)(i) or (r)(2)(F) of the act. The

comment argued that dietary ingredients

without established RDI’s are expressly

excluded by section 7(c) of the Dietary

Supplement Health and Education Act

of 1994 (the DSHEA) from the nutrient

content claims provisions found in

section 403(r)(2)(A)(i) of the act. The

comment interpreted section 7(c) of the

DSHEA to mean that nutrient content

claims can be made for dietary

ingredients that do not have RDI’s.

One comment suggested that the

codified language be revised to state

clearly that the term ‘‘antioxidant’’ is

being described solely as part of a

nutrient content claim. For example, the

comment suggested that proposed

§ 101.54(g) be revised to read ‘‘the term

‘antioxidants,’ when used as part of a

nutrient content claim, may only be

used on the label or in labeling * * *.’’

(Emphasis added.) The comment also

suggested that proposed § 101.54(g) be

revised to include the statement ‘‘This

section does not apply to dietary

supplement statements of nutritional

support.’’

FDA agrees with the first comment

that ‘‘antioxidant’’ describes the

biological activity of a substance. As

stated above, FDA has defined

‘‘antioxidant activity’’ in § 101.54(g)(2)

(under its authority under sections

403(r)(2) and 701(a) of the act).

However, FDA does not agree that

‘‘antioxidant’’ is necessarily a statement

that is made under section 403(r)(6) of

the act. If an antioxidant effect is a

nutritional effect, that is, if it is

attributable to the nutritional value of

consuming a substance, a claim about

that substance’s antioxidant effect may

be made as long as it is truthful and not

misleading and not made in violation of

section 403(r)(1)(A) (on nutrient content

claims) or (r)(1)(B) (on health claims) of

the act.

Section 403(r)(6) of the act is relevant

only if the antioxidant effect is not

attributable to the nutritive value of the

dietary ingredient, or if a manufacturer

chooses to take advantage of this

provision even though the antioxidant

effect is attributable to a substance’s

nutritive value (see discussion on

section 403(r)(6) of the act in the

nutrient content claims document

published elsewhere in this issue of the

Federal Register.) Section 403(r)(6) of

the act, which was added by the

DSHEA, encompasses label statements

on dietary supplements that claim a

benefit related to a classical nutrient

deficiency disease, describes how a

nutrient or dietary ingredient affects the

structure or function in humans,

characterizes the documented
49876 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

mechanism by which a nutrient or

dietary ingredient acts to maintain the

structure or function, or describes

general well-being from consumption of

a nutrient or dietary ingredient.

Manufacturers may make claims

regarding the antioxidant properties (or

biological properties) of a substance

under section 403(r)(6) of the act as long

as all of the requirements of this section

of the act are met (e.g, notification,

substantiation, disclaimer).

The agency rejects the comment that

suggested that section 403(r)(2)(F) of the

act is relevant to this rulemaking.

Section 403(r)(2)(F) of the act creates a

narrow exception to section

403(r)(2)(A)(i) of the act. Section

403(r)(2)(F) of the act pertains only to

claims about the percentage of a dietary

ingredient for which FDA has not

established a reference value. Thus,

section 403(r)(2)(F) of the act has no

relevance to this proceeding. (See the

nutrient content claims document

published elsewhere in this issue of the

Federal Register for further discussion

of percentage claims.)

As discussed in comment 6 of this

document, FDA is persuaded to revise

the paragraph heading for § 101.54(g) to

state that the section refers to nutrient

content claims using the term

‘‘antioxidants’’ to clarify that the section

addresses nutrient content claims for

antioxidants. The agency concludes that

this revision clarifies that the scope of

§ 101.54(g) is limited to nutrient content

claims without making the additional

changes in codified language suggested

by the comment.

B. Beta-carotene

9. Several comments agreed with the

inclusion of beta-carotene in the

antioxidant definition. Several other

comments opposed its inclusion. The

latter comments provided two reasons

for their opposition: (1) There is little

scientific evidence that beta-carotene

functions as an antioxidant in the

human body, and (2) findings from

clinical prevention trials suggest

potential harm to smokers from the

consumption of beta-carotene

supplements. One comment stated that

in the Alpha-Tocopherol, Beta Carotene

(ATBC) Lung Cancer Prevention Trial

(the ATBC Trial), an intake of 20

milligrams (mg)/day synthetic betacarotene over a 5- to 8-year period was

associated with an 18 percent increased

incidence of lung cancer and an 8

percent increase in total mortality in

male smokers (Ref. 16). The comment

also noted that the Beta-Carotene and

Retinol Efficacy Trial (CARET) was

terminated early because interim results

indicated that beta-carotene and vitamin

A supplements provided no benefit and

may have caused harm to participants

(Ref. 17). The comment reported that in

the CARET trial, 30 mg beta-carotene

and 25,000 International Units (IU)

vitamin A were administered daily to

male and female smokers and former

smokers or to men exposed to asbestos.

The comment noted that the interim

result, a 28 percent increased lung

cancer risk in the treatment group, was

consistent with the results of the ATBC

Trial. The comment asserted that results

of these studies do not support the

hypothesis that beta-carotene provides

any beneficial disease prevention or

antioxidant effect in these populations.

Furthermore, the comment maintained

that the evidence from the Physician’s

Health Study, which showed no

protective effect from beta-carotene

supplementation against cancer or

cardiovascular disease (Ref. 18), clearly

does not support an antioxidant role for

beta-carotene in the prevention of these

diseases.

Another comment argued that the

scientific evidence does not support the

hypothesis that beta-carotene

supplements are effective in the

prevention of cancer or cardiovascular

disease in well-nourished populations.

The comment, however, asserted that

the question of a possible increase in

risk of disease among smokers who take

beta-carotene supplements had not been

definitively proven.

One carotenoid expert asserted that

carotenoids are more appropriately

defined as ‘‘physiologic modulators’’

rather than as ‘‘antioxidants.’’ An

antioxidant expert contended that there

is inadequate scientific evidence to

support the hypothesis that betacarotene functions as an antioxidant in

the human body and urged FDA not to

include beta-carotene in this

classification until scientific evidence is

available to support its purported action

as an antioxidant.

A couple of comments stated that

there is no evidence demonstrating a

significant in vivo antioxidant function

for beta-carotene, compared to the

demonstrated in vivo antioxidant

function for vitamins C and E. The

comments stated that the results of the

beta-carotene intervention trials do not

support an antioxidant function for

beta-carotene but, instead, indicate that

beta-carotene supplementation may

cause harm to smokers, possibly

through a pro-oxidant mechanism.

These comments stated that there is no

consensus among experts that betacarotene has in vivo antioxidant

activity.

Another comment cited the findings

of the ATBC trial and suggested that

beta-carotene may act as a pro-oxidant

at high levels. The comment further

stated that negative health effects or prooxidant activity results have not been

attributed to high intakes of mixed

carotenoids provided from fruits and

vegetables. The comment also stated

that foods with naturally occurring betacarotene contain a mixture of

carotenoids and carotenoid isomers that

may confer a health protective effect to

foods compared to supplements

containing only beta-carotene. The

comment agreed with the inclusion of

beta-carotene in the antioxidant

definition but suggested that the agency

prohibit dosages that would result in

pro-oxidant stress. The comment

suggested that when beta-carotene is the

subject of the claim, the product should

contain at least 20 percent, but no more

than 100 percent, of the RDI for vitamin

A as added beta-carotene.

As discussed in the previous

comment, FDA is not specifically

identifying beta-carotene as an

antioxidant in this final rule. However,

FDA does not agree with the comments

that stated that beta-carotene should not

be considered a recognized antioxidant

and therefore should be ineligible to be

included in nutrient content claims for

antioxidants. There is substantial

scientific evidence that beta-carotene, in

addition to its established metabolic

role as a precursor to vitamin A, acts as

an antioxidant (Refs. 19 through 22).

The agency is aware, however, that most

of the scientific evidence for beta

carotene having antioxidant activity is

from in vitro, rather than in vivo,

studies. Although there is no direct

scientific evidence that beta-carotene

has in vivo antioxidant activity, or that

it may have a beneficial health outcome

that is directly attributable to its

antioxidant capacity, the in vitro

antioxidant activity of beta-carotene

suggests mechanisms for how it and

other antioxidant substances may act in

the body. For example, the results from

a recent study suggest that vitamin E,

vitamin C, and beta-carotene collaborate

to deactivate free radicals (Ref. 23).

Investigators reported that, using an in

vitro model, free radicals are passed

from one antioxidant molecule to the

next in the following sequence: From

vitamin E to beta-carotene to vitamin C.

These investigators hypothesized that

the resulting water-soluble, vitamin C

radical would be voided from the body

before causing harm. According to this

scheme, smokers, who tend to have

lower levels of vitamin C than

nonsmokers, do not have sufficient

vitamin C to scavenge the carotenoid

radicals. The investigators raised the
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49877

possibility of low vitamin C levels in

smokers as an explanation for the

increased risk of lung cancer following

beta-carotene supplementation that was

found in the ATBC and CARET trials.

Findings from clinical trials do not

reveal the exact mechanism of action of

substances in vivo, but they do provide

information on whether a compound

can achieve a particular clinical

outcome or endpoint. Clinical trials can

provide clues on whether the substance

acted in the hypothesized fashion.

Because of the adverse results of the

ATBC and CARET trials, the agency

recognizes that beta-carotene may have

other than antioxidant effects in certain

situations. It may be that beta-carotene

acts as a pro-oxidant in certain

situations, e.g., in smokers given large

doses of supplemental beta-carotene,

but as an antioxidant in others, e.g., in

nonsmoking, healthy adults who

consume diets high in beta-carotene.

The agency believes that additional

research on the in vivo antioxidant

mechanism of beta-carotene is needed,

and if future scientific evidence does

not support an in vivo antioxidant effect

for beta-carotene, the agency is prepared

to reconsider whether this substance

meets the definition of antioxidant.

Thus, while the results from in vitro

studies do not conclusively prove that

beta-carotene is an in vivo antioxidant,

they provide enough scientific evidence

that the agency concludes that it is

reasonable, at this time, to permit betacarotene to be the subject of nutrient

content claims about the level of

antioxidants in food.

FDA agrees with those comments that

stated that the results of the ATBC and

CARET trials raise serious concerns

about the safety of beta-carotene

supplementation for smokers and others

at high risk of lung cancer. Based on the

comments discussed above and on

FDA’s review of the scientific literature,

the agency advises that it has serious

concerns about the safety of dietary

supplements that are intended to

provide 20 mg or more beta-carotene

daily, the lowest dose for which an

adverse effect was observed in the

ATBC trial. The agency encourages

manufacturers and distributors of

dietary supplements containing betacarotene to consider the safety of

dosages in excess of this amount in

developing and marketing such

products and to consider including

cautionary label statements to ensure

that such high-dose beta-carotene

dietary supplements do not present a

significant or unreasonable risk of injury

or illness to consumers under the

conditions of use recommended or

suggested in labeling or under ordinary

conditions of use. FDA points out that

it agrees with the comment that stated

no negative health effects have been

attributed to high intakes of carotenoids,

including beta-carotene, from fruits and

vegetables.

C. Complete and Complex

10. Several comments objected to the

proposed definition of ‘‘complete’’ and

‘‘complex.’’ One comment

recommended that the proposed

standard for ‘‘complete’’ or ‘‘complex’’

antioxidant formula be strengthened by

mandating that vitamin C and vitamin E

be present at 100 percent or more of RDI

levels, and that at least 100 percent of

the RDI for vitamin A be present as betacarotene.

One comment recommended that

FDA permit the use of the term

‘‘antioxidant complex’’ with an asterisk

to refer to another asterisk next to a list

of all antioxidant ingredients other than

vitamin E, vitamin C, and beta-carotene.

The comment suggested that the asterisk

correspond with a same panel reference

to the following statement: ‘‘This

product contains —————, which are

antioxidants. An RDI reference amount

has not been established for these

nutrients.’’ The comment stated that

‘‘complete antioxidant complex’’ is

inherently misleading, and that only

‘‘antioxidant complex’’ should be used

as a collective term. The comment

maintained that ‘‘complete antioxidant

complex’’ conveys the impression that

the product contains all known

antioxidant compounds and contains

those compounds at 100 percent of their

RDI’s.

One comment stated that the purpose

of the definition is limited solely to

define nutrient content claims, and FDA

is not purporting to define what other

dietary ingredients play an antioxidant

role in the body and which claims

(other than defined nutrient content

claims) may be made. For this reason,

the comment objected to the proposed

definitions of ‘‘complex’’ and

‘‘complete’’ because they do not

characterize a level, which is the

prerequisite for a claim under section

403(r)(1)(A) of the act. The comment

maintained that limiting the use of these

terms to even an expanded list of

nutrients with RDI’s would be

misleading in light of the growing

scientific recognition of the antioxidant

capabilities of a number of other dietary

ingredients.

Another comment stated that

authorizing a claim such as ‘‘complete

antioxidant formula’’ will result in an

infringement of a federally-registered

trademark. Several associations of

advertising agencies stated that the use

of such terms undercuts the value of

certain trademarked terms.

Based on the comments, FDA is

persuaded that terms such as ‘‘complete

antioxidant complex’’ and ‘‘complete

antioxidant formula,’’ discussed in the

high potency/antioxidant proposal (60

FR 67184 at 67191), may convey the

impression that all known antioxidants

are present in a product. The agency is

persuaded that products bearing the

term ‘‘complete’’ in association with the

term ‘‘antioxidants’’ may be misleading

given the dictionary definition of

‘‘complete’’ (i.e., having all necessary

parts, whole) (Ref. 24). This term might

be misleading because a complete list of

antioxidants would be difficult to

compile and would likely be

controversial because of lack of

consensus of which substances are

antioxidants. On the other hand, the

term ‘‘complex’’ means composed of

interconnected or interwoven parts (Ref.

24) and conceivably might be applied to

a number of antioxidants in the same

product. Additionally, FDA is

persuaded that such terms do not

necessarily describe the level of a

nutrient and therefore are outside the

realm of nutrient content claims.

As mentioned, the agency recognizes

that there are dietary ingredients that

are antioxidants, but for which label

reference values have not been

established. Because nutrient content

claims can only be made for those

dietary ingredients for which reference

values have been established,

antioxidants without such reference

values could not be the subject of a

nutrient content claim.

Although nutrient content claims can

only be made for those dietary

ingredients for which reference values

have been established, the agency has

no objection to manufacturer’s grouping

these substances parenthetically next to

the term ‘‘antioxidants’’ or to listing

them in association with an asterisk

elsewhere on the product label.

However, as discussed in comment 6 of

this document, there are constraints on

the use of the word ‘‘contains’’ because

it is a synonym for ‘‘good source,’’ a

defined nutrient content claim.

In light of the conclusion that

‘‘complete’’ and ‘‘complex’’ do not

necessarily describe a nutrient level, the

potential for misunderstanding these

claims (i.e., for assuming that all

antioxidants are present), and because

of possible, unanticipated trademark

issues, FDA is withdrawing proposed

§ 101.54(g)(3) on collective nutrient

content claims. If such terms are used

on a food label, FDA will evaluate

whether their use is false or misleading
49878 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

under sections 403(a) and 201(n) of the

act.

D. Referral Statements

11. One comment argued that while

referral statements are required on

conventional foods, such statements are

not necessary on dietary supplements,

especially when the lack of space on

most labels is considered. The comment

argued that, unlike conventional foods,

almost all dietary supplements are

purchased specifically for their

ingredients, and that consumers can be

expected to analyze nutrition

information without being reminded to

do so.

FDA is not persuaded to change the

requirement for the referral statement,

nor does it have the authority to do so.

Section 403(r)(2)(B) of the act states that

if a nutrient content claim is made, the

label or labeling of the food shall

contain, prominently and in immediate

proximity to such claim, the following

statement: ‘‘See ————— for nutrition

information.’’ Under section

403(r)(2)(B)(i) of the act, the blank must

identify the panel on which the

information described in the statement

may be found. While the DSHEA

implicitly recognizes that statements

that characterize the percentage level of

a dietary ingredient for which FDA has

not established a reference value are

nutrient content claims, and thus

exempts them from the requirement in

section 403(r)(2)(A)(i) of the act, it does

not exempt such statements from the

requirement in section 403(r)(2)(B) for

referral statements. Further, because the

use of nutrient content claims is entirely

voluntary, the agency is not persuaded

to establish special provisions for small

package size. Therefore, FDA has made

no change in its regulations in response

to this comment.

E. Ingredient Statements

12. One comment requested

clarification on the use of the term

‘‘antioxidant’’ in an ingredient

statement. The comment stated that an

ingredient statement should be allowed

to include the term ‘‘antioxidant mix’’

or ‘‘antioxidant formula’’ within

appropriate limits because it is the

common or usual name of a mixture of

vitamins C and E and beta carotene. The

comment maintained that food

manufacturers can purchase

prepackaged mixtures containing these

three nutrients. The comment suggested

that the term ‘‘antioxidant mix’’ has

become an established common or usual

name of a mixture of these vitamins and

argued that the ingredient statement

should be permitted to identify an

antioxidant mixture followed by the

individual ingredients in parenthesis,

‘‘Antioxidant mix (ascorbic acid

(vitamin C), DL–Alpha-tocopherol

Acetate (vitamin E), Beta Carotene)’’.

Section 403(i)(1) of the act states that

a food is misbranded unless its label

states the common or usual name of the

food. The comment did not provide any

information to persuade the agency that

the term ‘‘antioxidant mix’’ is an

established common or usual name.

Therefore, FDA rejects the suggestion

that the term ‘‘antioxidant mix’’ be

allowed in ingredient labeling.

Interested parties may petition the

agency to consider the term

‘‘antioxidant mix’’ as a common or

usual name. FDA points out that any

such petition should include

substantiation that the term is

recognized by consumers as a common

or usual name.

IV. Effective Date

13. Several comments requested that

the date of application be 18 months

after publication of the final rule. One

comment requested 12 months; another

suggested 24 months. The comments

expressed concern that manufacturers

have adequate time to bring products

into compliance.

This final rule is one of four final

rules on food labeling published in this

issue of the Federal Register. Three of

the final rules pertain to dietary

supplements, the fourth final rule

pertains to the uniform compliance date

for food regulations. Comments were

received on the three dietary

supplement rulemakings requesting an

extension of their respective dates of

application. Because FDA wishes to

minimize the impact of label changes on

manufacturers, the agency is persuaded

that it is reasonable to extend the

effective date for these rulemakings to

18 months following the publication

date. This amount of time is consistent

with the time period allowed for the

labels of conventional foods to comply

with the 1990 amendments. FDA is

addressing the issue of the effective date

in greater detail in the final rule entitled

‘‘Food Labeling: Statement of Identity,

Nutrition Labeling and Ingredient

Labeling of Dietary Supplements’’

published elsewhere in this issue of the

Federal Register.

V. Other Provisions

FDA did not receive any comments

that dealt specifically with the other

provisions of the proposal. In the

absence of any basis for doing

otherwise, FDA is adopting those

provisions, in particular, the

amendment to § 101.60(c)(1)(iii)(A) (21

CFR 101.60(c)(1)(iii)(A)), as proposed.

VI. Environmental Impact

The agency has previously considered

the environmental effects of this rule as

announced in the high potency/

antioxidant proposal (60 FR 67184). No

new information or comments have

been received that would affect the

agency’s previous determination that

there is no significant impact on the

human environment and that an

environmental impact statement is not

required.

VII. Paperwork Reduction Act

In the high potency/antioxidant

proposal, FDA stated its tentative

conclusion that the proposed rule

contains no reporting, recordkeeping,

labeling or other third party disclosure

requirements and asked for comments

on whether the proposed rule imposed

any paperwork burden. No comments

were received addressing the question

of paperwork burden. FDA concludes

that the labeling requirements in this

document are not subject to review by

the Office of Management and Budget

because they do not constitute a

‘‘collection of information’’ under the

Paperwork Reduction Act of 1995 (44

U.S.C. 3501 et seq.). Rather, the labeling

statements are a ‘‘public disclosure of

information originally supplied by the

Federal government to the recipient for

the purpose of disclosure to the public’’

(5 CFR 1320(c)(2)).

VIII. Benefit-Cost Analysis

FDA has examined the economic

implications of the final rule as required

by Executive Order 12866. Executive

Order 12866 directs agencies to assess

all 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).

Executive Order 12866 classifies a rule

as significant if it meets any one of a

number of specified conditions,

including having an annual effect on the

economy of $100 million or 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 final rule is not a

significant rule as defined by Executive

Order 12866.

FDA believes that many dietary

supplements currently marketed use the

terms ‘‘high potency’’ and ‘‘high in

antioxidants’’ to describe the level of

nutrients in the products. Without

rulemaking to define these terms,

manufacturers will not be able to
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49879

continue to use them. This regulation

will require that any manufacturer of

dietary supplements currently using the

terms ‘‘high potency’’ or ‘‘antioxidant’’

bear the costs of removing such

statements from their labels only if the

products do not meet the definition that

the agency is adopting. FDA has

information on the use of the terms

‘‘high potency’’ and ‘‘antioxidant’’ on

the labels of dietary supplements

provided by A. C. Nielsen. Using the

item names in the Nielsen data base,

FDA can determine products using the

terms for the following Nielsen product

categories: ‘‘Nutritional Supplements’’

(94); ‘‘Vitamins-Tonic-Liquid &

Powder’’ (3); ‘‘Vitamins-Multiple’’ (217);

‘‘Vitamins-B Complex with Vitamin C’’

(46); and ‘‘Minerals’’ (98). Although

FDA does not have information on the

Nielsen category ‘‘VitaminsRemaining,’’ the agency can make some

plausible assumptions. Although FDA

does not know the exact size of the

missing product category, based on

other information provided by Nielsen,

it does know that this category is at least

as big as the largest of the other

categories. Therefore, it is reasonable to

assume that the number of products

using the terms ‘‘high potency’’ or

‘‘antioxidant’’ is at least equal to the

greatest of the other categories.

Therefore, FDA estimates that there are

at least 675 supplements of vitamins

and minerals that use these terms in

their labeling.

FDA has no information to determine

how many of those products will be

reformulated, nor how many labels will

be redesigned, as a result of this

regulation. Firms whose labels do not

meet the definitions for the claims

established in this rulemaking will

decide between reformulation and

relabeling based on the relative costs of

each. FDA cannot predict the cost of

reformulating because it will depend on

the nutrients involved and, in the case

of ‘‘high potency’’, the degree to which

the level of the nutrient is below the

definition for the claim. FDA estimates

that the cost of a label redesign for these

types of products is approximately

$2,200 per label. If the labels of all 675

products are redesigned, then the costs

of this regulation will be $1.5 million.

However, to the extent that firms can

combine label changes attributable to

this rule with those attributable to the

dietary supplement nutrition labeling

regulations (and the fact that FDA has

made those regulations effective on the

same day as the regulations in this

rulemaking means that firms will have

a complete ability to do so), then the

costs of this rule will be greatly reduced.

Based on these estimates, FDA

concludes that the costs of this rule will

not be significant.

By defining the terms ‘‘high potency’’

and ‘‘high in antioxidants,’’ this rule

will benefit consumers by ensuring the

consistent use of these claims. However,

because FDA cannot predict the extent

to which manufacturers will take

advantage of the opportunity to use

these claims nor the value that

consumers place on the consistent use

of these claims, FDA cannot quantify

the benefits of this final rule.

IX. Small Entity Analysis

FDA has examined the economic

implications of the final rule as required

by the Regulatory Flexibility Act (5

U.S.C. 601–612). If a rule has a

significant impact on a substantial

number of small entities, the Regulatory

Flexibility Act requires that agencies

analyze options that would minimize

the economic impact of that rule on

small entities. Pursuant to the

Regulatory Flexibility Act (5 U.S.C.

605(b)), the Secretary of Health and

Human Services certifies that this final

rule might have a significant impact on

a substantial number of small entities.

A. Estimate and Description of the

Small Entities

According to the Regulatory

Flexibility Act, the definition of a small

entity is a business independently

owned and operated and not dominant

in its field. The Small Business

Administration has set size standards

for most business categories through use

of four-digit Standard Industrial

Classification codes. For dietary

supplements of vitamins and minerals,

a business is considered small if it has

fewer than 750 employees.

As stated in the previous section, FDA

has determined that there are

approximately 675 products that may

require label redesign or product

reformulation if they do not meet the

definitions established by this

regulation. Using Dun’s Market

Identifiers, FDA has determined that

half of these products are produced by

120 small entities.

B. Description of the Impacts

As stated earlier, FDA has no

information to determine how many of

these products will be reformulated, nor

how many labels will be redesigned as

a result of this regulation. Firms whose

labels do not meet the definitions for the

claims established in this rulemaking

will decide between reformulation and

relabeling based on the relative costs of

each. In addition, affected firms may

choose to reformulate the product if the

loss of the claim will result in a

significant reduction in sales. FDA

cannot predict the cost of reformulating

because it will depend on the nutrients

involved and, in the case of ‘‘high

potency,’’ the degree to which the level

of the nutrient is below the definition

for the claim. As stated in section VIII

of this document, FDA has determined

the cost of redesigning each label to be

$2,200.

The smallest affected entity for which

FDA has information has three

employees, annual sales of $120,000,

and produces one product potentially

affected by this regulation. If the

product will require label redesign, then

the cost of this regulation to that firm

will be a one-time cost of $2,200, or 1.8

percent of the firm’s annual sales. FDA

considers this potential cost to be

significant.

C. Compliance Requirements and

Necessary Skills

The Regulatory Flexibility Act also

requires agencies to describe the

projected reporting, recordkeeping, and

other compliance requirements of the

rule and the type of professional skills

necessary for preparation of the report

or record. As stated elsewhere in this

preamble, there are no reporting or

recordkeeping requirements of this rule.

Manufacturers desiring to use ‘‘high

potency’’ or ‘‘antioxidant’’ claims on the

labels of their products are only

required to ensure that the products

meet the definitions of the claims.

In the case of ‘‘high potency,’’

manufacturers must review the levels of

the nutrients for which the claim is

made and ensure that they are

sufficient. Because manufacturers are

required to report the levels in the

nutrition facts panel, no further analysis

of the product is necessary. If the levels

of the relevant nutrients are insufficient,

then the firm must either avoid using

the claim or alter the levels of the

nutrient to meet the established

definition.

In the case of the term ‘‘antioxidant’’

when used in nutrient content claims,

firms must simply know whether or not

the nutrient is one of the nutrients that

may be labeled ‘‘antioxidant’’ when

used in a nutrient content claim. No

special skills are required in this case.

D. Alternatives

FDA has examined the following

alternatives to the rule which may

minimize the significant economic

impact on small entities consistent with

the stated objectives.

1. Exempt Small Entities

One alternative for alleviating the

burden for small entities would be to
49880 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

exempt them from the provisions of this

rule. However, the majority of the firms

engaged in the manufacture of vitamin

or mineral supplements are small. Even

accounting for the fact that large firms

produce more products on average than

small firms, exempting small firms

would exempt a large proportion of

products. Although this option would

clearly eliminate the burden on small

firms, it would also result in a

significant reduction in the value to

consumers of standardizing these terms.

Therefore, FDA concludes that selecting

this alternative would defeat the

purpose of the regulation.

2. Lengthen the Compliance Period

As discussed elsewhere, the agency is

persuaded to make this final rule

effective 18 months following its

publication date because the agency

wishes to minimize the impact of label

changes on manufacturers. FDA

considered establishing a longer

compliance period for small entities.

However, within the 18-month

compliance period, all but the very

smallest entities will be required to

change their labels in response to

nutrition labeling and ingredient

labeling requirements. Thus,

lengthening this compliance period will

not result in any reduction in costs to

these firms because they are not likely

to opt to relabel their products twice

when they have the ability to combine

the necessary changes into one

relabeling effort.

X. References

The following references have been

placed on file in the Dockets

Management Branch (HFA–305), Food

and Drug Administration, rm. 1–23,

12420 Parklawn Dr., Rockville, MD

20857, and may be seen by interested

persons between 9 a.m. and 4 p.m.,

Monday through Friday.

1. Gennaro, A. R., ed., ‘‘Remington’s

Pharmaceutical Sciences,’’ 18th edition, pp.

697–699, Mack Publishing Co., Easton, PA,

1990.

2. USDA and DHHS, ‘‘Nutrition and Your

Health, Dietary Guidelines for Americans,’’

Washington, DC, Home and Garden Bulletin

No. 232, 4th ed., U.S. Government Printing

Office, 1995.

3. Food and Nutrition Board, Institute of

Medicine, National Academy of Sciences,

‘‘How Should the Recommended Dietary

Allowances be Revised,’’ Washington, DC,

National Academy Press, 1994.

4. Office of Food Labeling, Center for Food

Safety and Applied Nutrition, Food and Drug

Administration, ‘‘Food Labeling, Questions

and Answers,’’ August 1993.

5. Schmuck, A., A.-M. Roussel, J. Arnaud,

V. Ducros, A. Favier, and A. Franco,

‘‘Analyzed Dietary Intakes, Plasma

Concentrations of Zinc, Copper, and

Selenium, and Related Antioxidant Enzyme

Activities in Hospitalized Elderly Women,’’

Journal of the American College of Nutrition,

15:462–468, 1996.

6. Clark, L. C., G. F. Combs, Jr., B. W.

Turnbull, E. H. Slate, D. K. Chalker, J. Chow,

L. S. Davis, R. A. Glover, G. F. Graham, E.

G. Gross, A. Krongrad, J. L. Lesher, H. K.

Park, B. B. Sanders, C. L. Smith, and J. R.

Taylor; for the Nutritional Prevention of

Cancer Study Group, ‘‘Effects of Selenium

Supplementation for Cancer Prevention in

Patients with Carcinoma of the Skin,’’

Journal of the American Medical Association,

276:1957–1963, 1996.

7. Halliwell, B., ‘‘Antioxidants in Human

Health and Disease,’’ Annual Review of

Nutrition, 16:33–50, 1996.

8. Galley, H. F., J. Thornton, P. D. Howdle,

B. E. Walker, and N. R. Webster,

‘‘Combination Oral Antioxidant

Supplementation Reduces Blood Pressure,’’

Clinical Science 92:361–365, 1997.

9. Combs, G. F., Jr., ‘‘Should Intakes With

Beneficial Actions, Often Requiring

Supplementation, be Considered for RDAs?’’,

Journal of Nutrition, 126:2373S–2376S, 1996.

10. Hussein, O., M. Rosenblat, G. Refael,

and M. Aviram, ‘‘Dietary Selenium Increases

Cellular Glutathione Peroxidase Activity and

Reduces the Enhanced Susceptibility to Lipid

Peroxidation of Plasma and Low-Density

Lipoprotein in Kidney Transplant

Recipients,’’ Transplantation, 63:679–685,

1997.

11. Singh, R. B., U. C. Gupta, N. Mittal, M.

A. Niaz, S. Ghosh, and V. Rastogi,

‘‘Epidemiologic Study of Trace Elements and

Magnesium on Risk of Coronary Artery

Disease in Rural and Urban Indian

Populations,’’ Journal of the American

College of Nutrition, 16:62–67, 1997.

12. Bonithon-Kopp, C., C. Coudray, C. Berr,

P.-J. Touboul, J. M. Feve, A. Favier, and P.

Ducimetiere, ‘‘Combined Effects of Lipid

Peroxidation and Antioxidant Status on

Carotid Atherosclerosis in a Population Aged

59–71 Y: The EVA Study,’’ American Journal

of Clinical Nutrition, 65:121–127, 1997.

13. Bhuvarahamurthy, V., N.

Balasubramanian, and S. Govindasamy,

‘‘Effect of Radiotherapy and

Chemoradiotherapy on Circulating

Antioxidant System of Human Uterine

Cervical Carcinoma,’’ Molecular and Cellular

Biochemistry, 158:17–23, 1996.

14. Worthington, H. V., L. P. Hunt, R. F.

McCloy, I. MacLennan, and J. M. Braganza,

‘‘A Pilot Study of Antioxidant Intake in

Patients with Cholesterol Gallstones,’’

Nutrition, 13:118–127, 1997.

15. Ebadi, M., M. P. Leuschen, H. El

Refaey, F. M. Hamada, and P. Rojas, ‘‘The

Antioxidant Properties of Zinc and

Metallothionein,’’ Neurochemistry

International, 29:159–166, 1996.

16. Albanes, D. et al., for the AlphaTocopherol, Beta Carotene Cancer Prevention

Study Group, ‘‘The Effect of Vitamin E and

Beta Carotene on the Incidence of Lung

Cancer and Other Cancers in Male Smokers,’’

New England Journal of Medicine, 330:1029–

1035, 1994.

17. Omenn, G. S. et al., ‘‘Effects of a

Combination of Beta Carotene and Vitamin A

on Lung Cancer and Cardiovascular Disease,’’

New England Journal of Medicine, 334:1150–

1155, 1996.

18. Hennekens, C. H. et al., ‘‘Lack of Effect

of Long-Term Supplementation with Beta

Carotene on the Incidence of Malignant

Neoplasms and Cardiovascular Disease,’’

New England Journal of Medicine, 334:1145–

1149, 1996.

19. Sies, H., and W. Stahl, ‘‘Vitamins E and

C, -Carotene, and Other Carotenoids as

Antioxidants,’’ American Journal of Clinical

Nutrition, 62(suppl):1315S–1321S, 1995.

20. Palozza, P., and N. I. Krinsky,

‘‘Antioxidant Effects of Carotenoids in vivo

and in vitro: An overview,’’ In: Methods in

Enzymology: Carotenoids, Part A: Chemistry,

Separation, Quantitation, and Antioxidation,

Academic Press, San Diego, CA, 213:403–

420, 1992.

21. The Carotenoid Research Interactive

Group (CARIG), ‘‘Beta-Carotene and the

Carotenoids: Beyond the Intervention Trials,’’

Nutrition Reviews, 54:185–188, 1996.

22. Rock, C. L., R. A. Jacob, and P. E.

Bowen, ‘‘Update on the Biological

Characteristics of the Antioxidant

Micronutrients: Vitamin C, Vitamin E, and

the Carotenoids,’’ Journal of the American

Dietetic Association, 96:693–702, 1996.

23. Bohm, F., R. Edge, E. J. Land, D. J.

McGarvey, and T. G. Truscott, ‘‘Carotenoids

Enhance Vitamin E Antioxidant Efficiency,’’

Journal of the American Chemical Society,

119:621–622, 1997.

24. ‘‘Webster’s New Riverside University

Dictionary,’’ p.285, Houghton Mifflin, 1994.

List of Subjects in 21 CFR Part 101

Food labeling, Nutrition, Reporting

and recordkeeping requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 101 is

amended as follows:

PART 101—FOOD LABELING

1. The authority citation for 21 CFR

part 101 continues to read as follows:

Authority: Secs. 4, 5, 6 of the Fair

Packaging and Labeling Act (15 U.S.C. 1453,

1454, 1455); secs. 201, 301, 402, 403, 409,

701 of the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 321, 331, 342, 343, 348, 371).

2. Section 101.54 is amended by

revising the section heading and adding

new paragraphs (f) and (g) to read as

follows:

§ 101.54 Nutrient content claims for ‘‘good

source,’’ ‘‘high,’’ ‘‘more,’’ and ‘‘high

potency.’’

* * * * *

(f) ‘‘High potency’’ claims. (1)(i) The

term ‘‘high potency’’ may be used on the

label or in the labeling of foods to

describe individual vitamins or

minerals that are present at 100 percent

or more of the RDI per reference amount

customarily consumed.

(ii) When the term ‘‘high potency’’ is

used to describe individual vitamins or

minerals in a product that contains
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49881

other nutrients or dietary ingredients,

the label or labeling shall clearly

identify which vitamin or mineral is

described by the term ‘‘high potency’’

(e.g., ‘‘Botanical ‘X’ with high potency

vitamin E’’).

(2) The term ‘‘high potency’’ may be

used on the label or in the labeling of

a multiingredient food product to

describe the product if the product

contains 100 percent or more of the RDI

for at least two-thirds of the vitamins

and minerals that are listed in

§ 101.9(c)(8)(iv) and that are present in

the product at 2 percent or more of the

RDI (e.g., ‘‘High potency multivitamin,

multimineral dietary supplement

tablets’’).

(3) Where compliance with

paragraphs (f)(1)(i), (f)(1)(ii), or (f)(2) of

this section is based on a nutrient that

has been added to a food (other than a

dietary supplement), that fortification

shall be in accordance with the policy

on fortification of foods in § 104.20 of

this chapter.

(g) Nutrient content claims using the

term ‘‘antioxidant.’’ A nutrient content

claim that characterizes the level of

antioxidant nutrients present in a food

may be used on the label or in the

labeling of that food when:

(1) An RDI has been established for

each of the nutrients;

(2) The nutrients that are the subject

of the claim have recognized

antioxidant activity; that is, when there

exists scientific evidence that, following

absorption from the gastrointestinal

tract, the substance participates in

physiological, biochemical, or cellular

processes that inactivate free radicals or

prevent free radical-initiated chemical

reactions;

(3) The level of each nutrient that is

the subject of the claim is sufficient to

qualify for the § 101.54(b), (c), or (e)

claim (e.g., to bear the claim ‘‘high in

antioxidant vitamin C,’’ the product

must contain 20 percent or more of the

RDI for vitamin C). Beta-carotene may

be a subject of the claim when the level

of vitamin A present as beta-carotene in

the food that bears the claim is

sufficient to qualify for the claim. For

example, for the claim ‘‘good source of

antioxidant beta-carotene,’’ 10 percent

or more of the RDI for vitamin A must

be present as beta-carotene per reference

amount customarily consumed; and

(4) The names of the nutrients that are

the subject of the claim are included as

part of the claim (e.g., ‘‘high in

antioxidant vitamins C and E’’).

Alternatively, when used as part of a

nutrient content claim, the term

‘‘antioxidant’’ or ‘‘antioxidants’’ (as in

‘‘high in antioxidants’’) may be linked

by a symbol (e.g., an asterisk) that refers

to the same symbol that appears

elsewhere on the same panel of a

product label followed by the name or

names of the nutrients with recognized

antioxidant activity. The list of nutrients

shall appear in letters of a type size

height no smaller than the larger of onehalf of the type size of the largest

nutrient content claim or 1/16 inch.

3. Section 101.60 is amended by

revising paragraph (c)(1)(iii)(A) to read

as follows:

§ 101.60 Nutrient content claims for the

calorie content of foods.

* * * * *

(c) * * *

(1) * * *

(iii)(A) It is labeled ‘‘low calorie’’ or

‘‘reduced calorie’’ or bears a relative

claim of special dietary usefulness

labeled in compliance with paragraphs

(b)(2), (b)(3), (b)(4), or (b)(5) of this

section, or, if a dietary supplement, it

meets the definition in paragraph (b)(2)

of this section for ‘‘low calorie’’ but is

prohibited by §§ 101.13(b)(5) and

101.60(a)(4) from bearing the claim; or

* * * * *

Dated: September 11, 1997.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 97–24732 Filed 9–22–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Chapter I

[Docket No. 96N–0094]

Uniform Compliance Date for Food

Regulations

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule; response to

comments.

SUMMARY: The Food and Drug

Administration (FDA) is responding to

comments that were submitted in

response to a final rule establishing

January 1, 2000, as the uniform

compliance date for food labeling

regulations that the agency issues

between January 1, 1997, and December

31, 1998. FDA received three comments

in response to that final rule. The

agency is not making any changes in the

final rule in response to these

comments. January 1, 2000, remains the

uniform compliance date for food

labeling regulations that are issued

between January 1, 1997, and December

31, 1998.

EFFECTIVE DATE: December 27, 1996.

FOR FURTHER INFORMATION CONTACT:

Gerad L. McCowin, Center for Food

Safety and Applied Nutrition (HFS–

150), Food and Drug Administration,

200 C St. SW., Washington, DC 20204,

202–205–4561.

SUPPLEMENTARY INFORMATION:

I. Background

FDA has periodically announced

uniform compliance dates for new food

labeling requirements to minimize the

economic impact of label changes. In

1992, FDA suspended this practice

pending the issuance of regulations

implementing the Nutrition Labeling

and Education Act of 1990 (the 1990

amendments). In the Federal Register of

December 24, 1996 (61 FR 67710), FDA

issued a final rule (hereinafter referred

to as the December 24, 1996, final rule)

establishing January 1, 1998, as its new

uniform compliance date for all food

labeling regulations that are issued after

its publication and before January 1,

1997. FDA announced that it was

reinstating its previous practice of

periodically announcing, as final rules,

uniform compliance dates for food

labeling regulations. In the Federal

Register of December 27, 1996 (61 FR

68145) (hereinafter referred to as the

December 27, 1996, final rule), FDA

established January 1, 2000, as the

uniform compliance date for food

labeling regulations that are issued

between January 1, 1997, and December

31, 1998. Because FDA had already

provided notice and opportunity for

comment on the practice of establishing

uniform compliance dates by issuance

of a final rule announcing the date (see

61 FR 67710, December 24, 1996), the

agency found any further rulemaking

unnecessary. Nonetheless, under 21

CFR 10.40(e)(1), FDA provided an

opportunity until March 13, 1997, for

interested persons to comment on

whether the uniform compliance date of

January 1, 2000, should be modified or

revoked. In the December 27, 1996, final

rule, FDA advised that it would publish

a notice setting out the agency’s

conclusions concerning any comments

that it received in response to the final

rule or initiate notice and comment

rulemaking to modify or revoke the

uniform compliance date that the final

rule established.

FDA received three letters, each

containing one or more comments, from

trade associations in response to the

December 27, 1996, final rule. A

summary of these comments and the