Food Labeling: Health Claims; Antioxidant Vitamin A and Beta- Carotene and the Risk in Adults of Atherosclerosis, Coronary Heart Disease, and Certain Cancers

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket No. 98N-0428]

Food Labeling: Health Claims; Antioxidant Vitamin A and Beta-

Carotene and the Risk in Adults of Atherosclerosis, Coronary Heart

Disease, and Certain Cancers

AGENCY: Food and Drug Administration, HHS.

ACTION: Interim final rule.

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

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

relationship between antioxidant vitamin A and beta-carotene and the

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

cancers. This interim final rule is in response to a notification of a

health claim submitted under section 303 of the FDA Modernization Act

of 1997 (FDAMA). FDA has reviewed statements that the petitioner

submitted in that notification, and, in conformity with the

requirements of FDAMA, the agency is prohibiting the claim because the

statements submitted as the basis of the claim are not ``authoritative

statements'' of a scientific body, as required by FDAMA; therefore,

section 303 of FDAMA does not authorize use of this claim. As provided

for in section 301 of FDAMA, this interim final rule is effective

immediately upon publication.

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

September 8, 1998.

ADDRESSES: Submit written comments to the Dockets Management Branch

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

Rockville, MD 20852.

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

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

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

SUPPLEMENTARY INFORMATION:

I. The FDA Modernization Act of 1997

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

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

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

(r)(3) of the act (21 U.S.C. 343(r)(2) and (r)(3)) by adding new

paragraphs (r)(2)(G), (r)(2)(H), (r)(3)(C), and (r)(3)(D) to section

403 of the act (21 U.S.C. 343(r)(2)(G), (r)(2)(H), (r)(3)(C), and

(r)(3)(D), respectively), which provide for the use in food labeling of

nutrient content claims and health claims, respectively, based on

authoritative statements. FDAMA requires that a notification of the

prospective nutrient content claim or the prospective health claim be

submitted to FDA at least 120 days before a food bearing the claim may

be introduced into interstate commerce. FDAMA and its requirements are

discussed in more detail in ``Food Labeling: Health Claims; Antioxidant

Vitamins C and E and the Risk in Adults of Atherosclerosis, Coronary

Heart Disease, Certain Cancers, and Cataracts'' (hereinafter referred

to as ``Health Claims; Vitamins C and E''), which is published

elsewhere in this issue of the Federal Register. In particular, aspects

of the requirements for an ``authoritative statement'' that are

relevant to this rulemaking and FDA's review process for notifications

are discussed in sections I.A and I.B, respectively, of that document.

II. The Notification

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

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

notification from Weider Nutrition International, Inc., containing nine

prospective claims that were identified in the text of the notification

as health claims (Ref. 1). The notification included statements that

the submitter described as authoritative statements and a scientific

literature review for each claim. FDA has created nine separate

dockets, one for each of the nine claims and is issuing a separate

interim final rule responding to each claim.

This interim final rule addresses the second claim in the

notification. The notification included 11 statements that the

petitioner identified as authoritative statements on which the

following claim is based: ``Antioxidant vitamin A and beta-carotene may

reduce the risk in adults of atherosclerosis, coronary heart disease

and certain cancers. Sources of Vitamin A and beta-carotene include

red, yellow and green leafy vegetables, dairy products, and dietary

supplements.''

The first sentence of this claim will be discussed in greater

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

describes the relationship between vitamin A and beta-carotene and a

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

several prospective health claims. The second sentence, ``Sources of

Vitamin A and beta-carotene include red, yellow and green leafy

vegetables, dairy products, and dietary supplements,'' is not a health

claim. Given that the notification indicated that it was intended to be

a notification for health claims, this statement was not reviewed by

FDA. The submitter did not separately identify this statement as any

particular type of claim.

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

highlight that statements that appropriately constitute nutrient

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

dietary supplements. Moreover, statements that constitute dietary

guidance are also allowed provided the information is truthful and not

misleading as required by sections 403(a) and 201(n) of the act (21

U.S.C. 321(n)). These aspects of nutrient content claims and dietary

guidance are discussed in more detail in ``Health Claims; Vitamins C

and E,'' which is published elsewhere in this issue of the Federal

Register.

III. Basis for the Action

FDA has reviewed the notification submitted in support of the

prospective claim: ``Antioxidant vitamin A and beta-carotene may reduce

the risk in adults of atherosclerosis, coronary heart disease and

certain cancers.'' The agency has determined that none of the 11

statements submitted as the basis for this claim meets the requirements

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

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

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

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

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

for the agency's action on the notification follows:

First, FDA determined that the components required by section

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

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

each of the 11 statements cited in support of the claim may be

attributable either to an appropriate Federal scientific body or to an

employee or employees of such a body.

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

this document cites statements from: (1) A report on nutrition

monitoring prepared for the Department of Health and Human Services

(DHHS) and the U.S. Department of Agriculture (USDA); (2) an electronic

version provided on the Internet of ``Nutrition and Your Health:

Dietary Guidelines for Americans,''

[[Page 34093]]

recommendations developed by a group of Federal agencies and issued

jointly by DHHS and USDA; (3) electronic versions provided on the

Internet of four quarterly reports from USDA's Agricultural Research

Service (ARS) (statement 3, 7, 9, and 11); (4) electronic versions

provided on the Internet of two interpretative summaries from USDA/ARS

Technology Transfer Information Center (statements 4 and 10); (5)

public information provided on the Internet by an institute of the

National Institutes of Health (NIH); (6) public information provided on

the Internet by USDA/ARS Beltsville Human Nutrition Research Center;

and (7) public information provided on the Internet by the National

Cancer Institute (NCI), an institute within NIH. Thus, nine statements

in the notification are attributable to either NIH or USDA/ARS. A 10th

statement is attributable to USDA and DHHS and is intended for use by

Federal agencies including NIH, the Centers for Disease Control and

Prevention (CDC), and USDA/ARS. An 11th statement from the Dietary

Guidelines for Americans is attributable to a group of Federal agencies

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

are highlighted in the statute as Federal scientific bodies. FDA

believes that USDA/ARS is also a scientific body of the U.S. Government

with official responsibility for public health protection or research

directly relating to human nutrition for the purposes of section

403(r)(2)(G) and (r)(3)(C) of the act. The agencies that were

identified as users of the ``Nutrition Monitoring Report'' as well as

the group that developed the dietary guidelines included Federal

agencies that are such scientific bodies, including NIH, CDC, and USDA/

ARS. Accordingly, the statements provided in the notification in

support of the claim may be attributable to appropriate Federal

scientific bodies or to their employees.

Finally, however, none of the 11 statements discussed in sections

III.A through III.K of this document was found to be an authoritative

statement.

A. Statement 1

Statement 1 reads: ``Beta-carotene and other pro-vitamin a

carotenoids can be converted to vitamin A in the body. Interest in the

carotenoids has increased in recent years because of the accumulation

of a large body of evidence that foods high in carotenoids are

protective against a variety of epithelial cancers.'' The notification

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

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

statement is found in a discussion on vitamins that is contained in

``Nutrition Monitoring in the United States--An Update Report on

Nutrition Monitoring'' that was prepared for USDA and the Public Health

Service of DHHS by the Life Sciences Research Office (SRO) of the

Federation of American Societies for Experimental Biology (FASEB) (DHHS

Publication No. (PHS) 89-1255, September 1989, 71). The notification

provided a photocopy of selected pages from the report.

The statement indicates that there is interest in the relationship

because of a growing body of evidence, but does not confirm that the

relationship is considered scientifically valid or well established.

Rather, the context suggests that further research would be worthwhile

and that the scientific evidence about the relationship is preliminary

or inconclusive, as described in section I.A.3 of ``Health Claims;

Vitamins C and E,'' which is published elsewhere in this issue of the

Federal Register.

The agency notes that the report was prepared under a DHHS contract

by LSRO/FASEB, an organization that is neither a Federal Government

agency nor affiliated with the National Academy of Sciences (NAS).

Contractual activities involved in the preparation of the report were

overseen by several Federal agencies that participate in the National

Nutrition Monitoring System (NNMS). The report provides an independent

expert panel's review of the dietary and nutritional status of the U.S.

population, as well as the factors that determine status, based on

information available through the NNMS; the report is an advisory

document for the Government agencies. A disclaimer that appears on the

inside front cover of the report, which was not included in the

notification, states that, although the report was printed and

distributed as part of a series of reports from the NNMS, ``the

interpretations contained in this report do not necessarily express the

views or policies of the U.S. Government and its constituent agencies''

(Ref. 2). Additionally, as noted in the foreword of the report (page

vii), representatives of participating Federal Government agencies

``reviewed final drafts of the report for technical accuracy and

satisfaction of the scope of work'' (Ref. 2).

Given this disclaimer and the statement from the foreword, the

component of the submitter's notification that provided ``a concise

description of the basis upon which [the submitter] relied for

determining that the requirements of [403(r)(3)(C)(i)] have been

satisfied'' (as required by 403(r)(3)(C)(ii)(I) of the act) needed to

address why this statement was in fact an authoritative statement. It

did not. The disclaimer indicates that Federal Government agencies

cannot be considered to have ``published'' the report in the sense that

it represents official policy of the agencies, as discussed in section

I.A.2 of ``Health Claims; Vitamins C and E,'' which is published

elsewhere in this issue of the Federal Register. The foreword of the

report indicates that it may involve a deliberative review of the

scientific evidence about the dietary and nutritional status of the

U.S. population, but that it does not involve a deliberative review of

the scientific evidence about diet/disease relationships. Further, the

foreword indicates that the Federal agencies did not themselves conduct

a deliberative review of the scientific evidence necessary for the

statements in the report to be ``authoritative statements,'' as

described in section I.A.3 of ``Health Claims; Vitamins C and E,''

which is published elsewhere in this issue of the Federal Register, but

rather only a review for technical accuracy of a final draft of the

report itself.

FDA concludes that the statement is not an ``authoritative

statement'' because it indicates that the scientific evidence is

preliminary or inconclusive, that it does not reflect the official

policy of an appropriate scientific body, and that no appropriate

scientific body has conducted a deliberative review of the scientific

evidence.

B. Statement 2

Statement 2 reads: ``The antioxidant nutrients found in plant foods

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

presently of great interest to scientists and the public because of

their potentially beneficial role in reducing the risk of cancer and

certain other chronic diseases.'' The notification identified statement

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

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

electronic version of ``Nutrition and Your Health: Dietary Guidelines

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

hereinafter referred to as the ``dietary guidelines,'' issued jointly

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

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

consists of selected pages reprinted from the Internet information,

which identifies the seven dietary guidelines and gives background

[[Page 34094]]

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

guidelines reflect the findings of a panel of scientists concerning the

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

guidelines are based on a deliberative review of the scientific

evidence about the nutrient/disease relationships that the guidelines

address. The subject statement is found within the discussion that

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

products, vegetables, and fruits.''

The statement indicates that a relationship between antioxidant

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

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

the need for future research and suggests that whether a relationship

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

that there exists a scientifically sound relationship that should be

accorded a presumption of validity. This assessment is further

supported by the fact that the subject of the dietary guideline is the

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

specific impact of antioxidant nutrients, vitamin A and beta-carotene,

per se. FDA notes that, consistent with the dietary guidelines, the

agency has authorized a health claim for the relationship between

cancer and fruits and vegetables that contain vitamins A (as beta-

carotene) as well as vitamin C and dietary fiber (21 CFR 101.78).

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

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

because the statement indicates that the scientific evidence about the

relationship in question is preliminary or inconclusive, as discussed

in section I.A.3 of the Federal Register ``Health Claims; Vitamins C

and E,'' which is published elsewhere in this issue of the Federal

Register.

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

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

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

agencies to consult with it about whether the statement is an

authoritative statement because, as discussed previously, the wording

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

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

C. Statement 3

Statement 3 reads: ``If the findings hold up in further research,

eating more vegetables rich in beta-carotene and related carotenoids-

lutein and lycopene-may help people ward off a cold or flu as well as

protect from cancer * * *. The findings also suggest that carotenoid-

rich vegetables also stimulate the immune system.'' The notification

identified statement 3 as an ``authoritative statement'' for purposes

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

statement is found in Human Nutrition (quarterly reports of selected

research projects, 4th quarter 1996) issued by the USDA's ARS and

provided on the Internet (``http://www.ars.usda.gov/is/qtr/q496/

hn496.htm'' accessed on 12/3/97). Human Nutrition is a periodic

compilation of brief (one paragraph) descriptions of ongoing research

being conducted within the various ARS facilities. The subject

statement (submitted to the agency as a hardcopy reprint from the

Internet) appears in a description of research entitled: ``Daily

servings of dark green and deep yellow vegetables and tomatoes boost

immune response, a preliminary study suggests.'' The paragraph

describes the nature and outcome of one ARS study and is attributed to

Tim R. Kramer and Beverly Clevidence of the USDA Beltsville Human

Nutrition Research Center in Beltsville, MD. The agency notes that the

research is identified as a ``preliminary study.''

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

statement (i.e., ``if the findings hold up''), suggests that the

statement is based on preliminary research and that further study is

needed. As such, the statement appears to indicate that the scientific

evidence about the relationship is preliminary or inconclusive.

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

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

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

deliberative review of the scientific evidence regarding a relationship

between the nutrient and the disease in question (Ref. 3). USDA

explained that the ARS quarterly reports describe progress on

individual projects without a deliberative review of all relevant

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

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

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

evidence.

D. Statement 4

Statement 4 reads: ``This research involving cells provides data

which supports the general hypothesis that beta-carotene and lutein

protect cells by serving as antioxidants.'' The notification identified

statement 4 as an ``authoritative statement'' for purposes of making

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

found in a one paragraph interpretative summary of a research report

from Technology Transfer Information Center, TEKTRAN of USDA/ARS

entitled ``Beta-carotene and Lutein Protect the Plasma Membrane of

HEPG2 Human Liver Cells Against Oxidant-induced Damage,'' and provided

on the Internet (``http://www.nalusda.gov/ttic/tektran/data/000006/92/

0000069264.html'' accessed on 12/3/97) (ARS Report Number 69264). It

describes the nature and outcome of one study, which is attributed to

Keith J. Martin, Mark L. Failla, and James C. Smith, Jr.

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

and a disease or health-related condition'' because no disease is

identified in the statement. Therefore, FDA has concluded that the

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

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

403(r)(C)(3) of the act, as described in section I.A.1 of ``Health

Claims; Vitamins C and E,'' which is published elsewhere in this issue

of the Federal Register.

E. Statement 5

Statement 5 reads: ``[Antioxidants] may help prevent disease.

Antioxidants fight harmful molecules called oxygen free radicals, which

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

producing energy * * *. [S]ome studies show that antioxidants may help

prevent heart disease, some cancers, cataracts, and other health

problems that are more common as people get older.'' The notification

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

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

statement is found within an information piece entitled: ``Life

Extension: Science or Fiction?'' that is provided on the Internet by

the Administration on Aging and which includes statements from the

``Age Page'' of the National Institute on Aging (an Institute of the

NIH) (``http://www.aoa.dhhs.gov/aoa/pages/agepages/lifextsn.html''

accessed on 12/2/97). This electronically available information

(submitted to the agency as a hardcopy reprint from the Internet

information) is dated 1994, is approximately two standard printed pages

in length, and is described as being intended to inform the reader

about chemicals being studied that may play a role in aging and what

scientists have learned about them so far. Topics

[[Page 34095]]

covered include: Antioxidants, DNA, DHEA, and other hormones. Ten tips

for healthy aging are also included. The section on antioxidants is 14

sentences in length and includes the 3 sentences identified as the

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

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

recommendations can be made.''

FDA asked NIH whether the statement is an ``authoritative

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

an authoritative statement of NIH because it was prepared by an

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

deliberative review of scientific evidence regarding the nutrient-

disease relationship in question (Ref. 4). Therefore, FDA has concluded

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

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

review of the scientific evidence.

F. Statement 6

Statement 6 reads: ``As potent antioxidants, [lutein and lycopene]

are thought to contribute to the lower rates of heart disease, cancer

and other diseases of aging among populations that eat a lot of fruits

and vegetables.'' The notification identified statement 6 as an

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

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

information piece, ``BHNRC Success Stories,'' provided on the Internet

by USDA/ARS Beltsville Human Nutrition Research Center and entitled:

``Carotenoids Show Their Real Colors'' (``http://www.barc.usda.gov/

bhnrc/success.htm'' accessed on 12/4/97). This electronically available

information (submitted to the agency as a hardcopy reprint from the

Internet information) is undated. The section on carotenoids is three

brief paragraphs in length and describes the nature and outcome of a

single ARS study attributed to Tim Kramer and Beverly Clevidence. The

same study was also referenced in ARS's Human Nutrition quarterly

report as noted in the discussion of statement 3 in section III.C of

this document.

The context of the section, as well as the wording of the statement

(i.e., ``are thought''), suggests that the statement is based on

preliminary research and that further study is needed. As such, the

statement appears to indicate that the scientific evidence about the

relationship is preliminary or inconclusive.

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

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

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

deliberative review of the scientific evidence regarding a relationship

between the nutrient and the disease in question (Ref. 3). USDA

explained that the ARS ``BHNRC Success Stories'' describe progress on

individual projects without a deliberative review of all relevant

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

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

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

evidence.

G. Statement 7

Statement 7 reads: ``Researchers also found more evidence

suggesting that carotenes act as antioxidants to protect the body from

harmful oxidation. Antioxidants are thought to help prevent heart

attack, stroke and cancer. During the low-carotene stints, researchers

recorded several biochemical signs of oxidative damage.'' The

notification identified statement 7 as an ``authoritative statement''

for purposes of making the claim that is the subject of this

rulemaking. The statement is found in Human Nutrition (quarterly

reports of selected research projects, 4th quarter 1996) (see

discussion of statement 3 in section III.C of this document), which is

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

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

description of research entitled: ``Do carotenoids--the bright red,

yellow and orange pigments in fruits and vegetables--warrant a

Recommended Dietary Allowance?'' The paragraph describes the nature and

outcome of two ARS studies and is attributed to Betty Burri of the

Western Human Nutrition Research Center in San Francisco, CA. The

agency notes that the final sentence states: ``Further ARS studies will

try to shed more light on whether a specific minimum daily intake of

carotenoids is important for good health.''

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

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

on preliminary research and that further study is needed. As such, the

statement appears to indicate that the scientific evidence about the

relationship is preliminary or inconclusive.

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

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

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

deliberative review of the scientific evidence regarding a relationship

between the nutrient and the disease in question (Ref. 3). Therefore,

FDA has concluded that the statement is not an ``authoritative

statement'' under section 403(r)(C)(3) of the act because it is not

based on a deliberative review of the scientific evidence.

H. Statement 8

Statement 8 reads: ``[H]igh dietary carotene and possibly vitamins

C and E and folate are associated with reduced risk for cervical

cancer.'' The notification identified statement 8 as an ``authoritative

statement'' for purposes of making the claim that is the subject of

this rulemaking. The statement is found in information provided on the

Internet by the NCI, an institute of NIH, in an article entitled:

``Prevention of Cervical Cancer'' and disseminated as part of ``PDQ--

Detection & Prevention--Health Professionals'' (PDQ stands for

physicians data query) (``http://cancernet.nci.nih.gov/clinpdq/

screening/Prevention__of__cervical__ cancer__Physician.html'' accessed

on 12/1/97). This electronically available information (submitted as a

hardcopy reprint from the Internet information) is undated,

approximately nine standard printed pages in length, and is described

as intended for use by doctors and other health care professionals. The

subject sentence is one of several sentences summarizing research on

the intake of micronutrients and the risk of squamous intraepithelial

lesion (SIL) and cervical cancer.

FDA asked NIH whether this was an ``authoritative statement'' under

FDAMA. NIH responded that the statement was not an authoritative

statement of NIH and does not reflect consensus within NIH (Ref. 4).

NIH explained that the evidence was reviewed by an editorial board for

PDQ, and the majority of the members are not Federal employees. The

statements contained in PDQ were reported by NIH to be ``state of the

art'' educational statements developed by an editorial board that

assesses the levels of scientific evidence supporting the statements.

In this instance, the scientific evidence for the nutrient-disease

relationship was not considered to be strong since it was based on

observational studies. NIH reiterated that the statement is not the

product of consensus process within the NCI and the statement has not

undergone formal review and clearance by the Director of the National

Institutes of Health.

Therefore, FDA has concluded that the statement is not an

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

[[Page 34096]]

the act because it does not reflect consensus within NIH, as discussed

in section I.A.2 of ``Health Claims: Vitamin C and E,'' which is

published elsewhere in this issue of the Federal Register.

I. Statement 9

Statement 9 reads: ``[B]eta carotene or vitamin A supplements have

reversed pre-cancerous conditions in people's mouths.'' The

notification identified statement 9 as an ``authoritative statement''

for purposes of making the claim that is the subject of this

rulemaking. The statement is found in Human Nutrition (quarterly

reports of selected research projects, 3rd quarter 1995) (see

discussion of statement 3 in section III.C of this document), which is

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

www.ars.usda.gov/is/qtr/q395/hn395.htm'' accessed on 12/3/97) in a

description of research entitled: ``A daily dose of blue-green algae

Spirulina may help prevent cancer of the mouth, a study shows.'' The

paragraph describes the nature and outcome of an ARS study and is

attributed to Padmanabhan P. Nair of the Beltsville Human Nutrition

Research Center, Beltsville, MD.

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

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

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

deliberative review of the scientific evidence regarding a relationship

between the nutrient and the disease in question (Ref. 3). Therefore,

FDA has concluded that the statement is not an ``authoritative

statement'' under section 403(r)(C)(3) of the act because it is not

based on a deliberative review of the scientific evidence.

J. Statement 10

Statement 10 reads: ``Carotenoids or other plant components appear

to boost the immune system.'' The notification identified statement 10

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

is the subject of this rulemaking. The statement is found in a one-

paragraph interpretative summary of a research report from Technology

Transfer Information Center, TEKTRAN of USDA/ARS entitled:

``Consumption of Carotenoid-Rich Vegetables Increases T-Lymphocyte

Proliferation and Plasma Levels of Carotenoid Oxidation Products'' and

provided on the Internet (``http://www.nalusda.gov/ttic/tektran/data/

000007/41/0000074185.html'' accessed on 12/3/97) (ARS Report Number

74185). It describes the nature and outcome of one study, which is

attributed to ten researchers, the first author being Beverly

Clevidence.

FDA finds that the statement is not ``about the relationship

between a nutrient and a disease or health-related condition'' because

no disease is identified in the statement. Therefore, FDA has concluded

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

condition and therefore is not an ``authoritative statement'' under

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

K. Statement 11

Statement 11 reads: ``A wealth of epidemiological evidence has

linked a high intake of green leafy and deep yellow vegetables--both

rich in beta- carotene--with lower rates of many types of cancer * * *.

Men over 65 who took a 50-milligram beta-carotene supplement every

other day during the 12-year study had natural killer cells that were

more active than their counterparts who got a placebo. Natural killer

cells--or NK cells--are the immune system's sentinels, ever on watch

for viruses and cancer cells.'' The notification identified statement

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

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

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

1996) (see discussion of statement 3 in section III.C of this

document), which is issued by the USDA's ARS and provided on the

Internet (``http://www.ars.usda.gov/is/qtr/q496/hn496.htm'' accessed on

12/3/97) in a description of research entitled: ``Older people who get

plenty of beta carotene may have a better chance of preventing virus

infections or a cancerous growth.'' The paragraph describes the nature

and outcome of a study and is attributed to Simin Nikbin Meydani of the

USDA Human Nutrition Research Center on Aging at Tufts, Boston, MA.

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

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

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

deliberative review of the scientific evidence regarding a relationship

between the nutrient and the disease in question (Ref. 3). Therefore,

FDA has concluded that the statement is not an ``authoritative

statement'' under section 403(r)(C)(3) of the act because it is not

based on a deliberative review of the scientific evidence.

In summary, FDA has concluded that the notification does not

include any authoritative statements published by a scientific body as

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

claim relating to the relationship between antioxidant vitamin A and

beta-carotene and the risk in adults of atherosclerosis, coronary heart

disease, and certain cancers is not authorized under section

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

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

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

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

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

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

21 CFR 10.70 to authorize the health claim or claims by regulation

under section 403(r)(3)(B).

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

and Opportunity for Public Comment

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

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

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

added by section 301 of FDAMA, provides that FDA ``may make proposed

regulations issued under [section 403(r)] effective upon publication

pending consideration of public comment and publication of a final

regulation'' if the agency ``determines that such action is necessary *

* * to enable [FDA] to act promptly to ban or modify a claim'' under

section 403(r) of the act. For purposes of judicial review, ``[s]uch

proposed regulations shall be deemed final agency action.'' The

legislative history indicates that the agency should issue rules under

this authority as interim final rules (H. Conf. Rept. No. 105-399, at

98 (1997)).

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

determined that the statements submitted in support of the prospective

health claim do not meet the requirements for authoritative statements

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

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

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

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

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

will consider modifications to this interim final rule based on

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

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

(address above) written comments regarding this interim

[[Page 34097]]

final rule. Comments must be received by that date. Two copies of any

comments are to be submitted, except that individuals may submit one

copy. Comments are to be identified with the docket number found in

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

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

V. Environmental Impact

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

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

effect on the human environment. Therefore, neither an environmental

assessment nor an environmental impact statement is required.

VI. Analysis of Economic Impacts

A. Benefit-Cost Analysis

FDA has examined the impacts of this interim final rule under

Executive Order 12866. Executive Order 12866 directs Federal agencies

to assess the costs and benefits of available regulatory alternatives

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

maximize net benefits (including potential economic, environmental,

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

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

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

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

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

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

finds that this interim final rule is not a significant regulatory

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

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

purpose of congressional review.

If in the future FDA authorizes health claims relating to the

relationship between antioxidant vitamin A and beta-carotene and the

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

cancers after finding that there is significant scientific agreement

about these relationships, the cost to consumers of prohibiting this

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

information from appearing in food labeling that would ultimately be

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

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

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

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

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

relationship information in that labeling has been shown to be

scientifically valid.

A health claim relating to the relationship between antioxidant

vitamin A and beta-carotene and the risk in adults of atherosclerosis,

coronary heart disease, and certain cancers has not been authorized

under existing regulations. The prohibition of this claim in this

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

therefore no costs to firms are attributable to this interim final

rule.

B. Small Entity Analysis

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

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

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

minimize the economic impact of their regulations on small businesses

and other small entities. In compliance with the Regulatory Flexibility

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

impact on a substantial number of small entities.

A health claim related to the relationship between antioxidant

vitamin A and beta-carotene and the risk in adults of atherosclerosis,

coronary heart disease, and certain cancers has not been authorized

under existing regulations. The prohibition of this claim in this

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

therefore this interim final rule will not result in a significant

increase in costs to any small entity. Therefore, this interim final

rule will not have a significant economic impact on a substantial

number of small entities. Accordingly, under the Regulatory Flexibility

Act (5 U.S.C. 601-612), the agency certifies that this interim final

rule will not have a significant economic impact on a substantial

number of small entities.

C. Unfunded Mandates Reform Act of 1995

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

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

interim final rule does not trigger the requirement for a written

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

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

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

private sector, in any 1 year.

VII. The Paperwork Reduction Act of 1995

This interim final rule contains no collections of information.

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

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

VIII. References

The following references have been placed on display in the Dockets

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

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

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

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

Nutrition International, Inc., February 23, 1998.

2. LSRO, FASEB, ``Nutrition Monitoring in the United States--An

Update Report on Nutrition Monitoring,'' prepared for USDA and DHHS,

DHHS Pub. No. (PHS) 89-1255, PHS, DHHS, U.S. Government Printing

Office, Washington, DC, inside front cover and pp. iii to vii,

September, 1989.

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

USDA, May 7, 1998.

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

Harlan, NIH, April 30, 1998.

Dated: June 16, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98-16455 Filed 6-19-98; 8:45 am]

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