[Federal Register Volume 63, Number 119 (Monday, June 22, 1998)]
[Rules and Regulations]
[Pages 34097-34101]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-16456]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket No. 98N-0427]


Food Labeling: Health Claims; B-Complex Vitamins, Lowered 
Homocysteine Levels, and the Risk in Adults of Cardiovascular Disease

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 B-complex vitamins (folic acid, vitamin 
B<INF>6</INF>, vitamin B<INF>12</INF>), lowering elevated serum 
homocysteine levels, and the risk in adults of cardiovascular disease. 
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

[[Page 34098]]

petitioner submitted in that notification, and, in conformity with the 
requirements of FDAMA, the agency is prohibiting the claim because the 
statements submitted as the basis of the claim are not ``authoritative 
statements'' of a scientific body, as required by FDAMA; therefore, 
section 303 of FDAMA does not authorize use of this claim. As provided 
for in section 301 of FDAMA, this rule is effective immediately upon 
publication.

DATES: The interim final rule is effective June 22, 1998; comments by 
September 8, 1998.
ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Christine J. Lewis, Center for Food 
Safety and Applied Nutrition (HFS-451), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-205-4168.

SUPPLEMENTARY INFORMATION:

I. The FDA Modernization Act of 1997

    On November 21, 1997, the President signed FDAMA into law (Pub. L. 
105-115), which amended the Federal Food, Drug, and Cosmetic Act (the 
act). Sections 303 and 304 of FDAMA amended section 403(r)(2) and 
(r)(3) of the act (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 a companion document in this issue of the 
Federal Register (see ``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''). 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 third claim in the 
notification. The notification included four statements that the 
submitter identified as authoritative statements on which the following 
claim is based: ``B-complex vitamins-Folic Acid, Vitamin B<INF>6</INF>, 
Vitamin B<INF>12</INF>--may reduce the risk in adults of cardiovascular 
disease by lowering elevated serum homocysteine levels, one of the many 
factors implicated in that disease. Sources of B-complex vitamins 
include whole and enriched grains, green leafy vegetables, fish, dry 
beans, red meat, and dietary supplements.''
    The first sentence of this claim will be discussed in greater 
detail section III of this document. The second sentence, ``Sources of 
B-complex vitamins include whole and enriched grains, green leafy 
vegetables, fish, dry beans, red meat, 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) (21 U.S.C. 321(n)) 
of the act. 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: ``B-complex vitamins--Folic Acid, Vitamin 
B<INF>6</INF>, Vitamin B<INF>12</INF>--may reduce the risk in adults of 
cardiovascular disease by lowering elevated serum homocysteine levels, 
one of the many factors implicated in that disease.'' The agency has 
determined that none of the four 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 four 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 four statements from quarterly reports from the 
U.S. Department of Agriculture's (USDA) Agricultural Research Service 
(ARS) from electronic versions provided on the Internet. Thus, the 
statements in the notification are all attributable to USDA's ARS. FDA 
believes that USDA/ARS is 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. Accordingly, the statements 
provided in the notification in support of the claim may be 
attributable to an appropriate Federal scientific body or to its 
employees.
    Finally, however, none of the four statements discussed in sections 
III.A through III.D of this document was found to be an authoritative 
statement.

A. Statement 1

    Statement 1 reads: ``A research team's new evidence confirms 
earlier data that elevated levels of the amino acid homocysteine 
increase the odds for significant narrowing of the arteries * * * The 
Analysis also Showed that Insufficient Levels of Folate and, to a 
Lesser Extent, Vitamin B<INF>6</INF> contribute to increased risk of 
artery narrowing. Like a see-saw, homocysteine levels go up as the 
vitamins go down, and vice versa.'' The notification identified 
Statement 1

[[Page 34099]]

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, 1st quarter 
1995) issued by the USDA's ARS and provided on the Internet (``<a href="http://
www.ars.usda.gov/is/qtr/q195/hn195.htm">http://
www.ars.usda.gov/is/qtr/q195/hn195.htm</a>'' accessed on 12/4/97). 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: ``Eating green vegetables, citric and other foods 
rich in folate (folic acid) may help keep the arteries open, reducing 
heart disease and stroke risks.'' The paragraph describes the nature 
and outcome of one ARS study and is attributed to Jacob Selhub and Paul 
Jaques of the Jean Mayer USDA Human Nutrition Research Center on Aging 
at Tufts.
    FDA 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. 2). USDA 
explained that the ARS Quarterly Reports describe progress on 
individual projects without a deliberative review of all relevant 
scientific evidence. Therefore, FDA has concluded that the statement is 
not an ``authoritative statement'' under section 403(r)(3)(C) of the 
act because it is not based on a deliberative review of the scientific 
evidence, as described in section I.A.3 in ``Health Claims; Vitamins C 
and E,'' which is published elsewhere in this issue of the Federal 
Register.

B. Statement 2

    Statement 2 reads: ``When people don't have enough of these 
[vitamin B<INF>12</INF> and folate] vitamins to metabolize homocysteine 
it accumulates in the blood and damages the vessels.'' The notification 
identified Statement 2 as an ``authoritative statement'' for purposes 
of making the claim that is the subject of this rulemaking. The 
statement is found in Human Nutrition (quarterly reports of selected 
research projects, 4th Quarter 1996) (see discussion of statement 1 in 
section III.A of this document), which is issued by the USDA's ARS and 
provided on the Internet (``<a href="http://www.ars.usda.gov/is/qtr/q496/
hn496.htm">http://www.ars.usda.gov/is/qtr/q496/
hn496.htm</a> accessed'' on 12/3/97) in a description of research entitled: 
``One or two alcoholic drinks a day can interfere with people's B 
vitamin levels, according to a study of 41 men and women.'' The 
paragraph describes the nature and outcome of one ARS study and is 
attributed to Judith Hallfrisch of the USDA Beltsville Human Nutrition 
Research Center on Aging.
    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. 2). 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.

C. Statement 3

    Statement 3 reads: `` [T]he body needs [folate] to convert 
homocysteine into a nontoxic amino acid and thus prevent damage to 
blood vessels * * * Supplement users had the lowest homocysteine levels 
but not much lower than frequent consumers of fruits, vegetables and 
cereal.'' 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) (see 
discussion of statement 1 in section III.A of this document), which is 
issued by the USDA's ARS and provided on the Internet (``<a href="http://
www.ars.usda.gov/is/qtr/q496/hn496.htm">http://
www.ars.usda.gov/is/qtr/q496/hn496.htm</a>'' accessed on 12/3/97) in a 
description of research entitled: ``Eating more fruits, vegetables, and 
cold cereal fortified with folic acid--a form of folate--should 
significantly reduce the risk of heart disease and stroke that comes 
from having high blood levels of homocysteine, a new study shows.'' The 
paragraph describes the nature and outcome of one ARS study and is 
attributed to Katherine L. Tucker of the Jean Mayer 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. 2). 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.

D. Statement 4

    Statement 4 reads: ``Research has linked high homocysteine levels 
to increased risk of heart disease and stroke.'' 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 Human Nutrition (quarterly reports of selected 
research projects, 3d Quarter 1995) (see discussion of Statement 1 in 
section III.A of this document), which is issued by the USDA's ARS and 
provided on the Internet (``<a href="http://www.ars.usda.gov/is/qtr/q395/
hn395.htm">http://www.ars.usda.gov/is/qtr/q395/
hn395.htm</a>'' accessed on 12/3/97) in a description of research entitled 
``Measuring blood levels of the amino acid homocysteine only after an 
overnight fast could miss nearly half of the people with elevated 
levels.'' The paragraph describes the nature and outcome of one ARS 
study and is attributed to Andrew G. Bostom and Jacob Selhub of the 
Jean Mayer 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. 2). Therefore, 
FDA has concluded that the statement is not an ``authoritative 
statement'' under section 403(r)(3)(C) of the act because it is not 
based on a deliberative review of the scientific evidence.
    In summary, FDA has concluded that the notification does not 
include any authoritative statement published by a scientific body of 
the U.S. Government as required by section 403(r)(3)(C) of the act. 
Accordingly, the subject claim relating to the relationship between B-
complex vitamins (folic acid, vitamin B<INF>6</INF>, vitamin 
B<INF>12</INF>), lowering elevated serum homocysteine levels, and the 
risk in adults of cardiovascular disease 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 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 a claim, an 
interested person may petition the

[[Page 34100]]

agency under section 403(r)(4) of the act and 21 CFR 101.70 to 
authorize a health claim by regulation under section 403(r)(3)(B) of 
the act.

IV. Issuance of an Interim Final Rule, Immediate Effective Date, 
and Opportunity for Public Comment

    For the reasons described in this section, 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. 105-399, at 98 
(1997)).
    As described in section III of this document, FDA has determined 
that the statements submitted in support of the prospective health 
claim do not meet the requirements for authoritative statements in 
section 403(r)(3)(C) of the act. FDA has determined that it is 
necessary to act promptly to prohibit the claim's use under section 
403(r)(3)(C) of the act, and, accordingly, is issuing this interim 
final rule to ban its use under section 403(r)(3)(C) of the act.
    FDA invites public comment on this interim final rule. The agency 
will consider modifications to this interim final rule based on 
comments made during the comment period. Interested persons may, on or 
before September 8, 1998, submit to the Dockets Management Branch 
(address above) written comments regarding this interim final rule. 
Comments must be received by that date. Two copies of any comments are 
to be submitted, except that individuals may submit one copy. Comments 
are to be identified with the docket number found in brackets in the 
heading of this document. Received comments may be seen in the office 
above between 9 a.m. and 4 p.m., Monday through Friday.

V. Environmental Impact

    The agency has determined under 21 CFR 25.30(k) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VI. Analysis of Economic Impacts

A. Benefit-Cost Analysis

    FDA has examined the impacts of this interim final rule under 
Executive Order 12866. Executive Order 12866 directs Federal agencies 
to assess the costs and benefits of available regulatory alternatives 
and, when regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, 
public health and safety, and other advantages; distributive impacts; 
and equity). According to Executive Order 12866, a regulatory action is 
``significant'' if it meets any one of a number of specified 
conditions, including having an annual effect on the economy of $100 
million; adversely affecting in a material way a sector of the economy, 
competition, or jobs; or if it raises novel legal or policy issues. FDA 
finds that this interim final rule is not a significant regulatory 
action as defined by Executive Order 12866. In addition, it has been 
determined that this interim final rule is not a major rule for the 
purpose of congressional review.
    If in the future FDA authorizes health claims relating to the 
relationship between B-complex vitamins (folic acid, vitamin 
B<INF>6</INF>, vitamin B<INF>12</INF>), lowering elevated serum 
homocysteine levels, and the risk in adults of cardiovascular disease 
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 B-complex 
vitamins (folic acid, vitamin B<INF>6</INF>, vitamin B<INF>12</INF>), 
lowering elevated serum homocysteine levels, and the risk in adults of 
cardiovascular disease has not been authorized under existing 
regulations. The prohibition of this claim in this interim final rule 
results in no regulatory changes for firms, and therefore no costs to 
firms are attributable to this interim final rule.

B. Small Entity Analysis

    FDA has examined the impacts of this interim final rule under the 
Regulatory Flexibility Act. The Regulatory Flexibility Act (5 U.S.C. 
601-612) requires Federal agencies to consider alternatives that would 
minimize the economic impact of their regulations on small businesses 
and other small entities. In compliance with the Regulatory Flexibility 
Act, FDA finds that this interim final rule will not have a significant 
impact on a substantial number of small entities.
    A health claim relating to the relationship between B-complex 
vitamins (folic acid, vitamin B<INF>6</INF>, vitamin B<INF>12</INF>), 
lowering elevated serum homocysteine levels, and the risk in adults of 
cardiovascular disease has not been authorized under existing 
regulations. The prohibition of this claim in this interim final rule 
results in no regulatory changes for firms, and therefore this rule 
will not result in a significant increase in costs to any small entity. 
Therefore, this rule will not have a significant economic impact on a 
substantial number of small entities. Accordingly, under the Regulatory 
Flexibility Act (5 U.S.C. 601-612), the agency certifies that this 
interim final rule will not have a significant economic impact on a 
substantial number of small entities.

C. Unfunded Mandates Reform Act of 1995

    FDA has examined the impacts of this interim final rule under the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). This 
interim final rule does not trigger the requirement for a written 
statement under section 202(a) of UMRA because it does not impose a 
mandate that results in an expenditure of $100 million or more by 
State, local, and tribal governments in the aggregate, or by the 
private sector, in any 1 year.

VII. The Paperwork Reduction Act of 1995

    This interim final rule contains no collections of information. 
Therefore, clearance by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520) is not required.

VIII. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.

[[Page 34101]]

    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. Letter to Christine Lewis, CFSAN, FDA, from Eileen Kennedy, 
USDA, May 7, 1998.

    Dated: June 16, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-16456 Filed 6-19-98; 8:45 am]
BILLING CODE 4160-01-F