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

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

B6, vitamin B12), 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 B6,

Vitamin B12--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

B6, Vitamin B12--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 B6 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 (``http://

www.ars.usda.gov/is/qtr/q195/hn195.htm'' 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 B12 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 (``http://www.ars.usda.gov/is/qtr/q496/

hn496.htm 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 (``http://

www.ars.usda.gov/is/qtr/q496/hn496.htm'' 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 (``http://www.ars.usda.gov/is/qtr/q395/

hn395.htm'' 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 B6, vitamin

B12), 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

B6, vitamin B12), 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 B6, vitamin B12),

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 B6, vitamin B12),

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]

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