[Federal Register Volume 62, Number 184 (Tuesday, September 23, 1997)]
[Rules and Regulations]
[Pages 49868-49881]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-24732]


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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