Law Library


Federal Register: September 23, 1997 (Volume 62, Number 184)

Rules and Regulations

Page 49868-49881

 

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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.

 

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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 Sec. 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

 

Page 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 Sec. 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

Sec. 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 Sec. 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

 

Page 49870

 

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 Sec. 101.13(b)(6),

which would have limited the use of ``high potency'' to dietary

supplements. FDA also is revising proposed Sec. 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 Sec. 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 Sec. 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 Sec. 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

Sec. 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 Sec. 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

Sec. 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 Sec. 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

 

Page 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

 

Page 49872

 

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 Sec. 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 Sec. 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

Sec. 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 Sec. 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

Sec. 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 Sec. 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

Sec. 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

Sec. 101.9(c)(8)(iii)). Accordingly, the agency is revising proposed

Sec. 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

Sec. 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

 

Page 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 Sec. 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

Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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).

 

Page 49874

 

    No evidence was presented in the comments that nutrient content

claims for vitamin C, vitamin E, and beta-carotene 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 Sec. 101.54 because

some nutrients with reported antioxidant activity (e.g., copper,

manganese, iron) are pro-oxidative 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 pro-oxidant 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 Sec. 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 Sec. 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 Sec. 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 beta-carotene 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 Sec. 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

Sec. 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'').

 

Page 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. One-sixteenth of an inch is specified in Sec. 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, one-sixteenth of an inch is the minimum size

required in Sec. 101.105(i) for net quantity of contents statements.

Consequently, the agency concludes that a minimum type size of one-

sixteenth 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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

 

Page 49876

 

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 Sec. 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 Sec. 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 beta-

carotene 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 beta-

carotene 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 beta-carotene 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 pro-oxidant 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 beta-carotene 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

 

Page 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

beta-carotene 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 beta-

carotene 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 beta-carotene.

    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 Sec. 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

 

Page 49878

 

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 Sec. 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

 

Page 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

``Vitamins-Remaining,'' 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

 

Page 49880

 

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 Alpha-Tocopherol, 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:

 

Sec. 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

 

Page 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

Sec. 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 Sec. 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 Sec. 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 one-half 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:

 

Sec. 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 Secs. 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