Food Labeling: Health Claims; Soluble Fiber From Certain Foods and Coronary Heart Disease

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket No. 96P-0338]

Food Labeling: Health Claims; Soluble Fiber From Certain Foods

and Coronary Heart Disease

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is announcing its

decision to authorize the use, on food labels and in food labeling, of

health claims on the association between soluble fiber from psyllium

seed husk and reduced risk of coronary heart disease (CHD). Based on

its review of evidence submitted with comments to the proposal, as well

as evidence described in the proposal, the agency has concluded that

soluble fiber from psyllium seed husk, similar to beta ()-

glucan soluble fiber from whole oats, when included as part of a diet

low in saturated fat and cholesterol, may reduce the risk of CHD by

lowering blood cholesterol levels. The agency has concluded, based on

the totality of publicly available scientific evidence, that there is

significant scientific agreement among qualified experts to support the

relationship between soluble fiber in psyllium seed husk and CHD.

Therefore, the agency has decided to amend the regulation that

authorized a health claim on soluble fiber from whole oats and the risk

of CHD to include soluble fiber from psyllium seed husk. FDA has

determined that label statements alerting consumers to the need to

consume adequate amounts of liquids with products containing dry or

incompletely hydrated psyllium will be required on products bearing the

health claim. FDA is announcing this action in response to a petition

filed by the Kellogg Co. (the petitioner).

DATES: This regulation is effective February 18, 1998. The Director of

the Office of the Federal Register approves of the incorporation by

reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of

certain publications in 21 CFR 101.81(c)(2)(ii)(B), effective February

18, 1998.

FOR FURTHER INFORMATION CONTACT: Virginia L. Wilkening, Center for Food

Safety and Applied Nutrition (HFS-165), Food and Drug Administration,

200 C St. SW., Washington, DC 20204, 202-205-5483.

SUPPLEMENTARY INFORMATION:

I. Background

On November 8, 1990, the Nutrition Labeling and Education Act of

1990 (the 1990 amendments) (Pub. L. 101-535) was signed into law. This

new law amended the Federal Food, Drug, and Cosmetic Act (the act) in a

number of important ways. One of the most notable aspects of the 1990

amendments was that they confirmed FDA's authority to regulate health

claims on food labels and in food labeling. FDA published final rules

implementing the 1990 amendments on January 6, 1993 (58 FR 2478). In

those final rules, FDA adopted Sec. 101.14 (21 CFR 101.14), which sets

out the rules for the authorization and use of health claims. The

agency also adopted Sec. 101.70 (21 CFR 101.70), which establishes a

process for petitioning the agency to authorize health claims about a

substance-disease relationship and sets out the types of information

that any such petition must include.

In addition, FDA conducted an extensive review of the evidence on

the 10 substance disease relationships listed in the 1990 amendments.

As a result of its review, FDA authorized a health claim in Sec. 101.77

(21 CFR 101.77) on the association between diets low in saturated fat

and cholesterol and high in vegetables, fruits, and grain products that

contain soluble fiber and a reduced risk of heart disease (58 FR 2552,

January 6, 1993). In that rulemaking, FDA reviewed the evidence

relating dietary fiber to heart disease and concluded that it was

difficult to determine the relationship because dietary fiber comprises

a diverse group of chemical substances that may be associated with

different physiological functions (58 FR 2552 at 2572). Chemically and

physiologically, cellulose, lignin, hemicellulose, pectin, and alginate

(all relatively purified fiber types) behave differently from one

another. Likewise, wheat bran, oat bran, and rice bran are not similar

in composition. The agency noted that the available evidence made it

difficult to correlate the role of specific fiber components to health

effects.

However, in its final rule, FDA noted that hypocholesterolemic

properties may be documented for specific food fibers (58 FR 2552 at

2567). Further, the agency stated that if manufacturers could document,

through appropriate studies, that dietary consumption of the soluble

fiber in their particular food has the effect of lowering low density

lipoprotein (LDL)-cholesterol, and has no adverse effects on other

heart disease risk factors (e.g., high density lipoprotein (HDL)-

cholesterol), they should petition for a health claim for their

particular product.

In accordance with the petition procedure in Sec. 101.70, FDA

published a final rule on the relationship between soluble fiber from

whole oats and reduced risk of heart disease (the soluble fiber from

whole oats final rule), Sec. 101.81 (21 CFR 101.81) (62 FR 3584,

January 23, 1997 and modified at 62 FR 15343, March 31, 1997). In that

document, the agency concluded that, based on the totality of publicly

available scientific evidence, there is significant scientific

agreement among qualified experts to support the relationship between

soluble fiber in whole oats and reduced risk of CHD. FDA also concluded

that the type of soluble fiber in whole oats, -glucan soluble

fiber, is the primary component responsible for the lowering of blood

total- and LDL-cholesterol associated with consumption of whole oat

products when part of a diet low in saturated fat and cholesterol. The

rule specified the chemical nature of the specific fiber and methods

for measuring its presence in foods.

In the soluble fiber from whole oats final rule, the agency

acknowledged the likelihood that consumption of -glucan

soluble fiber from sources other than whole oats, as well as soluble

fiber from other sources, will affect blood lipid levels and thus the

risk of heart disease (62 FR 3584 at 3587). At that time, FDA

considered structuring the final rule as an umbrella regulation

authorizing the use of a claim for ``soluble fiber from certain foods''

and risk of CHD. Such action would have allowed flexibility in

expanding the claim to other specific food sources of soluble fiber

when

[[Page 8104]]

consumption of those foods has been demonstrated to help reduce risk of

heart disease. However, the agency concluded that it was premature to

do so inasmuch as FDA had not reviewed the totality of evidence on

other, nonwhole oat sources of soluble fiber (62 FR 3584 at 3588).

Instead, the agency stated that because soluble fiber is a family of

very heterogeneous substances that vary greatly in their effect on risk

of CHD, a case-by-case approach is necessary as documentation is

developed through appropriate studies that a soluble fiber product has

an effect on blood total- and LDL-cholesterol levels and can therefore

be useful in reducing risk of CHD. To this end, FDA structured

Sec. 101.81 in such a way that, while the regulation covered -

glucan soluble fiber from whole oats, it could easily be amended as

evidence becomes available to support the use of the claim for other

sources of soluble fiber.

In the soluble fiber from whole oats final rule, FDA emphasized the

importance of the dietary component of the health claim, i.e., the

necessity for the whole oat product to be consumed as part of a low

saturated fat, low cholesterol diet, for a complete understanding of

the claim (62 FR 3684 at 3594). FDA stated that diets low in saturated

fat and cholesterol are considered by expert groups to be the most

effective dietary means of reducing heart disease risk, and that, while

soluble fiber from whole oats could contribute to this effect, its role

is generally recognized as being of smaller magnitude.

In the Federal Register of May 22, 1997 (62 FR 28234), and in

response to a petition filed under Sec. 101.70, the agency proposed to

amend Sec. 101.81 by adding psyllium seed husk as an additional source

of soluble fiber, thereby providing for health claims on the

association between soluble fiber from psyllium seed husk and reduced

risk of CHD (the psyllium husk proposed rule). In this proposed rule,

FDA considered the relevant scientific studies and data presented in

the petition as part of its review of the scientific literature on

soluble fiber from psyllium seed husk and heart disease. The agency

summarized this evidence in the proposed rule (62 FR 28234).

The psyllium husk proposed rule included qualifying criteria for

the purpose of identifying psyllium-containing foods eligible to bear

the proposed health claim. The proposal also specified mandatory

content and label information for health claim statements and provided

model health claims.

Section 101.81(c)(2)(ii) of the soluble fiber from whole oats

health claim regulation lists the sources of -glucan soluble

fiber for which FDA has evaluated data pertaining to effects on blood

cholesterol levels and has concluded that significant scientific

agreement exists regarding a relationship between soluble fiber in

whole oats and the risk of CHD. In the psyllium husk proposed rule, FDA

proposed to add new Sec. 101.81(c)(2)(ii)(B) to specify psyllium husk

as a source of soluble fiber eligible to be the subject of this claim.

Proposed Sec. 101.81(c)(2)(ii)(B)(1) identifies psyllium husk as the

dried seed coat (epidermis) of the seed of Plantago ovata, known as

blond or Indian psyllium, P. indica, or P. psyllium, and specifies that

the purity of the psyllium husk shall be no less than 95 percent, such

that it has 3 percent or less protein content, 4.5 percent or less of

light extraneous matter, and 0.5 percent or less of heavy extraneous

matter, but in no case may the combined extraneous matter exceed 4.9

percent, as determined by U.S. Pharmacopeia (USP) methods.

In its evaluation of the scientific evidence for a relationship

between consumption of soluble fiber from psyllium seed husk and blood

total- and LDL-cholesterol levels, the agency found no reliable data to

establish a dose-response for this relationship. However, the agency

did find that in placebo-controlled studies that tested an intake of

10.2 grams (g) of psyllium seed husk per day as a part of a diet low in

saturated fat and cholesterol, there were consistently significant

effects of psyllium husk on blood total- and LDL-cholesterol levels.

Therefore, the agency proposed to base the qualifying level of soluble

fiber from psyllium seed husk on a total daily intake of 10.2 g husk

(about 7 g of soluble fiber), as suggested by the petitioner.

Therefore, the proposed qualifying criterion in

Sec. 101.81(c)(2)(iii)(A)(2) was that the food provide at least 1.7 g

of soluble fiber from psyllium seed husk per reference amount

customarily consumed (RACC) (i.e., 7 g divided by 4 eating occasions

per day). The psyllium husk proposed rule also stated that if a

manufacturer can demonstrate that a diet low in saturated fat and

cholesterol that includes a blend of the eligible sources of soluble

fiber listed in Sec. 101.81(c)(2)(ii) has an effect on the risk of

heart disease, the manufacturer should petition to amend Sec. 101.81

further.

To reflect the agency's tentative decision to broaden Sec. 101.81

to include soluble fiber from psyllium seed husk, the agency proposed

to modify the section heading in Sec. 101.81 from ``Soluble fiber from

whole oats and risk of coronary heart disease'' to ``Soluble fiber from

certain foods and risk of coronary heart disease.'' Accordingly, the

agency also proposed to revise the statement ``soluble fiber from whole

oats'' to either ``soluble fiber from certain foods'' or ``soluble

fiber from the eligible food sources from paragraph (c)(2)(ii) of this

section'' where appropriate in Sec. 101.81. The agency did not propose

to modify the model claims.

II. Summary of Comments and the Agency's Responses

In response to the psyllium husk proposed rule, the agency received

19 letters, each containing one or more comments, from professional

organizations, industry, consumer groups, health care professionals,

and research scientists.

Approximately one-half of the comments that the agency received

agreed with one or more provisions of the psyllium husk proposed rule

without providing grounds for this support other than those provided by

FDA in the preamble to the psyllium husk proposed rule. A few of these

comments also requested modification of one or more provisions of the

proposed rule. Some comments provided additional data on the

relationship between psyllium husk soluble fiber and CHD. Some of the

comments that disagreed with the proposed rule provided specific

support for their positions. The agency has summarized and addressed

the relevant issues raised in all comments in the sections of this

document that follow.

A. Food Substance Associated With Reduced Risk of CHD

Health claims have two essential elements: A food substance and a

disease or health-related condition (Sec. 101.14). The agency proposed

to authorize a health claim on the relationship between consumption of

soluble fiber from psyllium husk, as part of a diet low in saturated

fat and cholesterol, and reduced risk of CHD. Further, the agency

proposed to amend the authorized claim for soluble fiber from whole

oats and CHD (Sec. 101.81) to include soluble fiber from psyllium husk

and to broaden the subject of the claim to ``soluble fiber from certain

foods'' and risk of CHD (62 FR 28234 at 28239).

1. Terminology

(Comment 1)

Comments received in response to the proposed rule used the term

``psyllium''

[[Page 8105]]

interchangeably with the terms ``psyllium seed husk'' and ``psyllium

husk.'' The agency also noticed that a few comments used the term

``psyllium'' when referring to the soluble fiber component of the

psyllium husk. Therefore, the agency finds it important to clarify the

terms that may be used in referring to the substance that is the

subject of this claim as well as the common or usual name of the

product that should be used in ingredient statements.

The substance that is the subject of this claim is soluble fiber of

the psyllium husk, i.e., the seed coat that has been removed from the

psyllium seed. It is the seed husk, rather than the seed, that is the

source of soluble dietary fiber. The purity specifications suggested by

the petitioner and adopted in proposed Sec. 101.81(c)(2)(ii)(B)(1)

refer to the extent to which psyllium husk has been separated from

residual seed components.

The agency notes that in the ingredient list of the petitioner's

psyllium husk-containing cereal the substance is declared as ``psyllium

seed husk'' (Ref. 1). The agency also notes that in the USP National

Formulary this substance is referred to as ``psyllium husk'' (Ref. 2).

The agency therefore considers both ``psyllium seed husk'' and

``psyllium husk'' to be common or usual names for the soluble dietary

fiber source that is the subject of this rule. In the psyllium husk

proposed rule, the agency used the term ``psyllium'' synonymously with

the term ``psyllium husk'' (62 FR 28234 at 28237). Upon further

consideration, the agency concludes that the term ``psyllium'' is not

sufficiently descriptive of the substance of this claim because this

term is likely to be construed as inclusive of the psyllium seed. The

psyllium seed includes nutrients and allergenic proteins that are not

components of psyllium husk. The psyllium husk purity specifications of

Sec. 101.81(c)(2)(ii)(B)(1) make the presence of psyllium seed in a

food a disqualifying criterion for foods eligible to bear the claim.

In this final rule, the agency is clarifying under

Sec. 101.81(c)(2) that the proper terms for the soluble fiber source

which is the substance of this rule are ``psyllium husk'' or ``psyllium

seed husk.'' Therefore, Sec. 101.81 (c)(2)(ii)(B)(1) is revised to read

``psyllium seed husk, also known as psyllium husk, shall have a purity

of * * *.'' Section 101.81 (c)(2)(ii)(B)(1), (c)(2)(ii)(B)(2), and

(c)(2)(iii)(A)(2) are revised to read ``psyllium husk'' where the term

``psyllium'' had been used in the proposed rule.

2. Eligibility of Psyllium Seed Husk

(Comment 2)

Some comments stated that psyllium husk is not a food and is not

consumed by itself. The comments stated that psyllium husk is an

ingredient or additive and, therefore, should not be eligible for a

health claim. One comment expressed concern that a health claim on a

food additive will put more reliance on food fortification or

supplementation as a strategy to improve health. The comment asserted

that the psyllium proposal represents a public policy shift that may

result in diverting attention from the importance of a varied selection

of foods.

FDA disagrees with comments that psyllium husk, as a food

ingredient, is not an appropriate substance for consideration of a

health claim. As discussed in the final rule implementing the 1990

amendments on the use of health claims (58 FR 2478 at 2480, January 6,

1993), a broad range of substances are potentially subject to

regulation under section 403 (r)(1)(B) of the act (21 U.S.C.

343(r)(1)(B)). Section 101.14(a)(2) was written to reflect this broad

coverage. Under the general requirements for health claims, the

substance that is the subject of the health claim can be either a

specific food or a component of food (Sec. 101.14(a)(2)). Moreover, the

fact that a substance may be a ``food additive,'' within the meaning of

that term in 21 CFR 170.3(g), does not preclude it from also being a

``substance'' under Sec. 101.14(a)(2). Although psyllium seed husk is

not consumed as a single food, it is a consumable portion of a seed

grain that is, or could be, used as a component of foods (e.g., cereal,

pasta, cookies, breakfast bars) and is a rich source of soluble fiber.

As such, psyllium seed husk is a ``substance'' within the meaning of

Sec. 101.14(a)(2) and thus eligible for consideration of a health

claim.

The agency also disagrees with the comment that the proposed health

claim represents a public policy shift in diverting attention from the

importance of a varied selection of foods by placing more reliance on

food fortification or supplementation to achieve public health goals.

The establishment of a health claim for soluble fiber from psyllium

husk and CHD, when viewed in conjunction with existing health claims

for fruits, vegetables, and grain products and CHD and for soluble

fiber from whole oats and CHD, emphasizes an important role (i.e.,

possible reduced risk of CHD) of an even wider variety of food

selections. It is important to note that the concept of formulating a

food product with psyllium seed husk is no different than formulating a

product with oat bran (another food ingredient supplying soluble fiber

that is the subject of an authorized health claim). As with oat bran,

the inclusion of psyllium husk in a food would be based on its basic

functional properties in addition to its nutritional contribution or

potential health benefit. The decision to include such an ingredient in

a food would be considered food product development, not fortification.

Therefore, the agency disagrees that the approval of this health claim

represents a public policy shift on food fortification.

B. Updated Review of Scientific Evidence and Issues Related to the

Evidence

Under Sec. 101.14(c), FDA will issue a regulation authorizing a

health claim only when it determines, based on the totality of publicly

available scientific evidence, that there is significant scientific

agreement that the claim is supported by such evidence. In its review

of the psyllium petition, the agency completed a comprehensive review

(see Ref. 7) of 21 human studies (Refs. 8 through 28) (62 FR 28234 at

28237). Of these, it gave particular weight to 7 studies (Refs. 13, 14,

15, 18, 22, 23, and 28) that were well designed and controlled and that

reported intakes of dietary saturated fat and cholesterol.

1. Data Submitted With Comments

(Comment 3)

One comment to the psyllium husk proposed rule noted that FDA

excluded from comprehensive review three studies (Ref. 12, 17, and 25)

because they lacked evidence that the study subjects were compliant

with a low saturated fat and cholesterol diet (i.e., the American Heart

Association ``Step 1'' diet). This comment submitted reports of

subsequent diet analyses of these studies indicating that study

subjects were compliant with the Step 1 diet (see Docket 96P-0338, C8).

This comment also noted that two unpublished studies included in the

psyllium petition have since been published or submitted for

publication (Refs. 12 and 25).

Another comment submitted five recently published studies for

consideration (Refs. 29 through 33) and three studies for

reconsideration (Refs. 14, 28, and 34). The latter were recently

published revisions of material submitted in the psyllium petition. The

comment stated that the published report by Jenkins et al. (Ref. 28)

contains additional data not presented in the

[[Page 8106]]

unpublished report submitted with the petition.

FDA, in reviewing the supplemental data for Refs. 12, 17, and 25,

concluded that this information shows the subjects of these three

studies were compliant with the dietary protocol and made no

significant changes to their diets throughout the duration of the

treatment period. Therefore, these studies have been added to the seven

studies to which the agency gave particular weight in evaluating the

relationship of soluble fiber from psyllium husk and CHD risk in the

psyllium husk proposed rule. These studies are summarized in Table 1 of

this document. The results of these three additional studies support

the relationship between consumption of soluble fiber from psyllium

seed husk and reduced risk of heart disease.

The agency also reviewed the published version of the study by

Jenkins et al. (Ref. 28) that was submitted in comments and has

summarized this study accordingly in Table 1 of this document. The

investigators evaluated the effect on serum lipid levels of two Step 2

metabolic diets that provided either 6 or 12 percent of energy from

monounsaturated fat (MUFA), approximately 60 g per day (/d) total

dietary fiber, and psyllium seed husk-containing cereal (mean intake of

11 g/d of psyllium seed husk) or wheat bran. The results showed

significantly lower total- and LDL-cholesterol levels in the psyllium

husk-supplemented groups compared to the control group at both MUFA

levels. The saturated fat intake during the two study periods was very

low (less than 6 percent of energy).

The agency did not conduct an in-depth review of five of the

studies submitted with comments. The study by Jensen and co-workers

(Ref. 33) does not meet the agency's criteria for study selection (62

FR 28234 at 28237) because the authors evaluated the usefulness of a

soluble fiber mixture (containing psyllium, pectin, guar gum, and

locust bean gum) in the long-term management of hypercholesterolemia.

The results of this study do not allow an evaluation of the effects of

soluble fiber from psyllium seed husk alone.

The experimental design of the study by Ganji and Kies (Ref. 32)

did not meet the agency's criteria for comprehensive review. In the

psyllium proposal, the agency stated that in evaluating a study, it

considered whether the intervention studies had been of long enough

duration to reasonably ensure stabilization of blood lipid levels

(i.e., greater than or equal to 3 weeks duration) (62 FR 28234 at

28237). In this study, diets were varied in four 7-day treatment

periods with no time between treatment periods. With this study design,

it cannot be determined whether the subjects' blood lipids had

stabilized to each diet or that there were no carryover effects from

one treatment period to another. Neither did the study design have an

adequate pre-intervention baseline period to ensure blood lipids had

stabilized to the base diet.

The other three studies submitted in comments that were not

reviewed indepth were animal studies (Refs. 29 through 31). Animal

studies are useful in studying mechanisms of action. However, the

agency relied primarily on the clinical studies in this rule. Such an

approach is consistent with that taken by the agency in its evaluation

of the relationship between soluble fiber from whole oats and risk of

CHD.

A meta-analysis (Ref. 34) was conducted to determine the effect of

psyllium seed husk-containing cereal products on serum lipid levels in

hypercholesterolemic subjects and to estimate the magnitude of the

effect among 404 subjects with mild to moderate hypercholesterolemia

(total-cholesterol of about 200 to 300 milligrams per deciliter (mg/dL)

who followed a low fat diet. In its review of the evidence submitted in

the psyllium petition, the agency reviewed 6 of the 11 studies (Refs.

11, 13, 22 through 24, and 28) included in the meta-analysis (see

tables in Ref. 7). The remaining studies used in the meta-analysis did

not meet the agency's criteria for study selection (62 FR 28234 at

28237). The conclusion of the meta-analysis report was that

hypercholesterolemic subjects who consumed the psyllium seed husk-

containing cereal had significantly lower total-cholesterol (about 5

percent) and LDL-cholesterol (about 9 percent) compared with those

subjects who consumed the control cereal (Ref. 34).

2. Totality of the Data on Soluble Fiber from Psyllium Seed Husk and

CHD

(Comment 4)

One comment stated that there was considerably more scientific data

on psyllium seed husk presented in the petition than that reviewed by

the agency. The comment noted that results of 56 studies were included

in the psyllium petition. The comment expressed concern that the agency

failed to consider studies published prior to 1988 and some additional

evidence made available since 1988, noting that studies with soluble

fiber mixtures, studies with treatment periods that were less than 3

weeks in duration, and abstracts were not selected for comprehensive

review. The comment stated that the agency began its review of the

scientific evidence by first considering the conclusions of the Surgeon

General's report and the Food and Nutrition Board/National Academy of

Sciences (FNB/NAS) report (Refs. 3 and 4) and then considered the

evidence that was made available since 1988. The comment explained that

neither the Surgeon General's report nor the FNB/NAS report reviewed

the evidence on psyllium up to 1988; therefore, the agency improperly

ignored a significant portion of the scientific evidence provided in

the petition (see Ref. 35, Table 3, pages 30 and 31). Another comment

noted that among the 56 studies submitted in the psyllium petition (see

Ref. 35), the results of only three failed to demonstrate that

consumption of psyllium-containing foods was associated with risk of

CHD through a reduction in serum cholesterol. The comment stated that

the totality of evidence on psyllium husk that was submitted in the

petition includes data on children and the elderly.

Some comments stated that it is premature to authorize a claim on

psyllium seed husk and risk of CHD because of a lack of significant

scientific agreement on this nutrient/disease relationship. Some of

these comments stated that the decision to propose this health claim is

based on evidence from a limited number of studies that overall covered

a small number of subjects, of which women were underrepresented, and

on the absence of data on certain subpopulations (children and the

elderly).

The agency agrees with the comment that the Surgeon General's

report (Ref. 3) and the FNB/NAS report (Ref. 4) did not review of all

of the psyllium studies that were publicly available prior to 1988 and

identified in the petition (Ref. 35). The petition identified 16

clinical studies, published prior to 1989, of the effect of psyllium

seed husk on blood cholesterol levels (see Ref. 35, Table 3). The

agency had not reviewed these studies in the psyllium husk proposed

rule, but in response to the comment, has subsequently considered them.

Half of these studies did not meet the agency's stated criteria for

selection of human studies (62 FR 28234 at 28237) in that they were

conducted in special populations, were published as abstracts only, or

the psyllium dose was unreported. Studies that used special population

groups were excluded from review because, as explained in the psyllium

husk proposed rule (62 FR 28234 at 28237), the results from such groups

may not be relevant to the general healthy U.S. population. The

[[Page 8107]]

agency's rationale for excluding from review studies presented only in

abstracts was also presented in the proposal. Abstracts do not provide

sufficient detail regarding the methodology and results to allow a

detailed assessment of the merits of the study. Likewise, information

regarding actual amounts of psyllium administered is a key detail of

the study design, without which an adequate assessment of the study

cannot be made.

In each of the pre-1989 clinical studies meeting the selection

criteria, there were aspects of the study design (e.g., lack of dietary

data, lack of a control group) that would have precluded the results of

these studies from having a major influence on the agency's

conclusions. Among the pre-1989 clinical studies was one double-blind

placebo-controlled psyllium husk study with dietary data (Ref. 36).

However, the report contained no evidence that the study subjects were

compliant with a low saturated fat and cholesterol diet. Thus, a review

by FDA of pre-1989 data would not have altered the conclusions reached

by the agency in the psyllium husk proposed rule nor contribute to

issuing the final rule.

The agency disagrees with the comments that there is not

significant scientific agreement that soluble fiber from psyllium husk

may help reduce the risk of CHD through its action on blood total- and

LDL-cholesterol levels. Some of the comments incorrectly suggested that

the agency's decision on this nutrient/disease relationship was based

solely on the results of the seven studies in Table 1 of the psyllium

husk proposed rule (62 FR 28234 at 28244). As stated previously, the

agency reviewed 21 human studies on psyllium (Refs. 8 through 28) that

were submitted with the petition and met the agency's criteria for

consideration (Ref. 7). Of these, the agency gave particular weight to

seven studies. As stated in the psyllium husk proposed rule, the

results of the seven studies (Refs. 13 through 15, 18, 22, 23, and 28),

and now three additional studies (Refs. 12, 17, and 25) (see comment 3

in section II.B.1 of this document), strongly support the relationship

between soluble fiber from psyllium husk and risk of CHD in mild to

moderate hypercholesterolemic adults (62 FR 28234 at 28238). Moreover,

the results of the remaining clinical studies (Refs. 8 through 11, 16,

19 through 21, 24, and 26) that were given less weight in the psyllium

husk proposed rule were consistent in showing an effect of soluble

fiber from psyllium husk on serum lipid levels. These studies included

both men and women subjects and adults of all ages, including the

elderly. It is on the totality of this evidence and conclusions from

the 1989 Life Sciences Research Office (LSRO) report on health

consequences of dietary fiber (Ref. 5) that the agency is basing its

conclusion to authorize a health claim on psyllium seed husk.

3. Psyllium Consumed as a Bulk Laxative

In the psyllium husk proposed rule, the agency included in its

evaluation the results of studies of this nutrient/disease relationship

in which psyllium was administered as a product marketed as a bulk-

forming fiber laxative.

(Comment 5)

Some comments were opposed to the consideration of studies in which

psyllium husk was supplied as a bulk-forming fiber laxative. One

comment stated that the use of studies in which psyllium seed husk was

consumed in different forms makes meaningful comparisons difficult.

Other comments had no objection to the agency's use of this evidence.

One comment stated that consuming psyllium husk as a bulk-forming fiber

laxative at mealtime is functionally equivalent to consuming a psyllium

husk-enriched food at mealtime. Another comment stated that clinical

studies evaluating psyllium seed husk administered as a bulk-forming

fiber laxative were conducted in a fashion similar to studies conducted

with food products, including consuming the substance at mealtime,

dietary counseling, and patient selection criteria. The comment stated

that both compliance with the regimen and efficacy were comparable for

food and laxative studies.

In the psyllium husk proposed rule, the agency tentatively decided

that including, in its comprehensive review, the three studies in which

psyllium seed husk was administered in the form used as a laxative

(Refs. 13, 15, and 18) was appropriate. In these studies, the psyllium

seed husk was consumed in concentrations similar to those at which

psyllium husk was incorporated into conventional foods in the other

studies selected for comprehensive review (Refs. 14, 22, 23, and 28)

(62 FR 28234 at 28238). The agency further noted that the magnitude of

the effect of soluble fiber from psyllium husk on the change in serum

lipid levels reported in the studies in which this substance was

consumed in conventional foods (Refs. 14, 22, 23, and 28) was similar

to that observed in the studies (Refs. 13, 15, and 18) in which it was

consumed as a bulk laxative. Therefore, the agency stated that the

results of the studies suggest that the form in which psyllium husk is

consumed is not significant when evaluating the effect of psyllium husk

on serum lipid levels (62 FR 28234 at 28238). Comments that were

opposed to reliance on studies which used a psyllium husk bulk-forming

laxative provided no new data to support their position. Therefore, the

agency is not persuaded that it is inappropriate to rely on this

evidence and concludes that studies that used a psyllium husk bulk-

forming laxative are appropriate in the evaluation of this nutrient/

disease relationship.

4. Studies in Subjects With Borderline to High Blood Cholesterol Levels

The subject populations in the studies reviewed in the psyllium

proposed rule (see Table 1, 62 FR 28234 at 28244) had borderline to

high blood total-cholesterol levels (i.e., average baseline cholesterol

values in the studies were between 225 and 275 mg/dL). The agency

tentatively concluded in the psyllium proposed rule that the studies

with hypercholesterolemic subjects are relevant to the general U.S.

population (62 FR 28234 at 28238) and requested comments on this issue.

(Comment 6)

Some comments agreed with the agency's view that studies of

populations with elevated blood cholesterol are relevant to the general

population. These comments cited current statistics of the incidence of

elevated blood cholesterol in the U.S. population, and noted that the

CHD risk factor that is the target of the proposed health claim is

elevated blood cholesterol. Other comments disagreed with the view that

the results of studies in hypercholesterolemics can be generalized to

the general population. One comment stated that because

hypercholesterolemic individuals are generally more responsive to

dietary intervention that normocholesterolemic individuals, it is

questionable whether normocholesterolemic persons would respond to

psyllium at all.

As the leading cause of death in this country, CHD is a disease for

which the general U.S. population is at risk. The risk of dying from

CHD is related to serum cholesterol levels in a continuous and positive

manner, increasing slowly for levels between 150 mg/dl and 200 mg/dl

and more rapidly when the cholesterol level exceeds 200 mg/dl (Ref.

37). The public health policy elucidated by the National Cholesterol

Education Program (NCEP), National Heart, Lung, and Blood Institute, is

to extend the benefits of cholesterol lowering to the population as a

whole by promoting adoption of eating patterns that can help lower the

blood cholesterol levels of most Americans

[[Page 8108]]

(Ref. 37). A dietary intervention that lowers blood cholesterol levels

only in persons with high levels would, like an intervention that

lowers cholesterol levels across the entire population range, cause a

shift in the population distribution of blood cholesterol levels

resulting in a decrease in the mean value for the blood cholesterol

level in the general population (Ref. 37). The anticipated effect of

such a shift would be to reduce the morbidity from CHD and to produce a

continued or accelerated decline in the CHD mortality rate in the

United States. The agency is persuaded by the evidence it has reviewed

in this rulemaking that the consumption of psyllium seed husk, as part

of a low saturated fat and cholesterol diet, can be a prudent public

health measure to assist in the national policy of promoting eating

patterns that will help in achieving or maintaining desirable blood

cholesterol levels in the general population. Therefore, it concludes

that the health claim is relevant to the general population and should

not be limited to a subpopulation of hypercholesterolemic individuals.

In addition, consistent with the agency's conclusions in rulemaking on

the dietary saturated fat and cholesterol/CHD claim (58 FR 2739 at

2745, January 6, 1993), the wording of the health claim as ``may' or

might' reduce the risk of heart disease'' adequately represents the

fact that not all persons will realize the same magnitude of benefit

from adopting the dietary change.

C. Issues Relative to Amending Sec. 101.81 to Include Soluble Fiber

From Psyllium Seed Husk

In the psyllium husk proposed rule, the agency tentatively

concluded that the soluble fiber in psyllium husk, like -

glucan soluble fiber from whole oats, when consumed as part of a diet

low in saturated fat and cholesterol, may help reduce the risk of heart

disease. Therefore, the agency proposed to amend the authorized claim

for -glucan soluble fiber from whole oats and risk of CHD

(Sec. 101.81) to include soluble fiber from psyllium husk and to

broaden the subject of the claim to ``soluble fiber from certain

foods'' and risk of CHD.

(Comment 7)

One comment stated that Sec. 101.81 should not be expanded to

include soluble fiber from psyllium husk because the eligible sources

of -glucan soluble fiber are whole grain foods that provide

nutrients in addition to soluble fiber, whereas psyllium seed husk,

which offers only soluble fiber, is neither a food nor a whole grain.

The comment also stated that psyllium seed husk should not be added to

Sec. 101.81 because the husk soluble fiber is separated from the whole

seed, whereas -glucan soluble fiber extracted from the whole

oat grain is not eligible for a claim. Two comments suggested that if

the claim must be structured as a soluble fiber claim, then only those

soluble fiber sources that elicit clinically significant reductions in

serum cholesterol via the same mechanism should be eligible to be

included in the claim.

FDA disagrees with the comment that substances qualifying for a

health claim under Sec. 101.81 must be whole grains similar to the

whole oats that are listed under Sec. 101.81(c)(2)(ii)(A). The subject

of the claim is soluble fiber and the food source of -glucan

soluble fiber is whole oats. There is no scientific basis to require

that only soluble fiber from whole grain foods can qualify for a claim.

The soluble fiber in psyllium seed is concentrated in the outer husk.

This is the opposite from whole oats where the soluble fiber is

concentrated in the inner portion of the oat groat. Moreover, purified

-glucan soluble fiber was not included as a substance eligible

to bear the claim because, as discussed in the whole oat final rule,

the hypocholesterolemic properties of -glucan fiber extracts

are affected by processing. Therefore, before an extract of -

glucan fiber could qualify for the claim, it would have to be

characterized so as to identify the processed form of the soluble fiber

that maintains its hypocholesterolemic properties. The data on psyllium

husk soluble fiber are associated with reduced risk of CHD via its

documented hypocholesterolemic properties. As discussed previously (see

comment 2 in section II.A.2 of this document), psyllium seed husk is a

``substance'' eligible for consideration of a health claim within the

meaning of that term in Sec. 101.14(a)(2). Therefore, the agency finds

it appropriate to consider soluble fiber from psyllium seed husk as a

source of soluble fiber that is eligible to be included in Sec. 101.81.

The agency also disagrees with the comment that a soluble fiber

source should not be included in Sec. 101.81 unless it elicits

reductions in serum cholesterol via the same mechanism as the

-glucan soluble fiber in whole oats. There is no scientific

basis to require soluble fibers to have the same mechanism of action

for lowering serum cholesterol in order to be eligible for a health

claim under Sec. 101.81, nor did the comments provide such a basis. In

the whole oat final rule, the agency stated that if a manufacturer can

document that a soluble fiber product has an effect on blood lipid

levels, and thereby can be useful in reducing the risk of CHD, the

manufacturer may petition to amend Sec. 101.81 to include that type of

soluble fiber-containing product as an eligible food source (62 FR 3584

at 3588). In this rulemaking, the agency has concluded that consumption

of soluble fiber from psyllium seed husk has an effect of lowering

blood total- and LDL-cholesterol levels, and therefore an amendment to

Sec. 101.81 to include psyllium seed husk as a soluble fiber source is

eligible for a health claim under Sec. 101.81.

D. Specifications for Psyllium Seed Husk

Based upon information provided by the petitioner, the agency

proposed a minimum psyllium husk purity specification as a qualifying

criterion for eligible sources of soluble fiber from psyllium. Proposed

Sec. 101.81(c)(2)(ii)(B)(1) stated that psyllium husk shall have a

purity of:

no less than 95 percent, such that it contains 3 percent or less

protein, 4.5 percent or less of light extraneous matter, and 0.5

percent or less of heavy extraneous matter, but in no case may the

combined extraneous matter exceed 4.9 percent * * *.

(62 FR 28234 at 28243).

1. Issues Relative to Psyllium Seed Husk Specifications

(Comment 8)

One comment noted that there are no assurances that food

manufacturers other than the petitioner will be able to meet the

petitioner's product specifications and therefore a compliance

monitoring program needs to be developed prior to authorization of the

health claim. A comment noted that due to natural variability in

psyllium seed husk and analytical variation, a ``94 percent purity''

specification would better represent the practical limit of

commercially-available ``95 percent purity'' psyllium. Accordingly,

this comment urged FDA to adopt a minimum psyllium husk purity of 94

percent with 5.0 percent or less of light extraneous matter and 1.0

percent or less of heavy extraneous matter. One comment expressed

concern that the purification of psyllium husk may render psyllium

inactive as a hypocholesterolemic agent. This comment also urged FDA to

determine whether the purification process described by the petitioner

should serve as the approved purification technique for psyllium.

The agency disagrees with the comment that a specific compliance

monitoring system is needed for psyllium seed husk. The monitoring and

[[Page 8109]]

verification of compliance with current good manufacturing practice in

the manufacture of human food is a routine FDA activity. The comment

urging the agency to change the psyllium husk purity specification to

``no less than 94 percent'' provided no data to substantiate that

commercial supplies of psyllium seed husk do not routinely meet the 95

percent purity specification and the agency sees no compelling reason

to revise the proposed purity specifications. Accordingly, the agency

is adopting the specifications proposed in Sec. 101.81(c)(2)(ii)(B)(1).

The agency notes that evidence provided in the petition and in

comments indicates that the psyllium seed husk in the food and bulk

laxative products used in the clinical studies, which were discussed in

the psyllium husk proposed rule, had a purity of at least 95 percent.

The blood cholesterol lowering effect of psyllium seed husk is

attributed to the soluble fiber content of the husk and not to the seed

components. As such, the concern that the process of separating the

psyllium husk from residual seed components would alter the

effectiveness of psyllium husk in lowering blood cholesterol level is

unfounded. The agency further notes that it has proposed to adopt a

psyllium husk purity specification only, and not a purification

process.

E. Nature of the Food Eligible to Bear the Claim

In the proposal, the agency determined a qualifying level of

psyllium husk for foods eligible to bear a soluble fiber and CHD claim

based on a daily intake of approximately 7 g of soluble fiber from

psyllium seed husk (62 FR 28234 at 28240). The agency stated that the

level of daily intake of soluble fiber from psyllium seed husk (7 g/d

was not based on the results of data from a dose-response study, but

was the amount shown in clinical studies to be consistently associated

with significant reductions in serum lipids in conjunction with a diet

low in saturated fat and cholesterol. Therefore, the agency proposed

that the qualifying level of soluble fiber for foods to bear a soluble

fiber and CHD claim be 1.7 g of soluble fiber from psyllium seed husk

per RACC (7 g divided by 4 eating occasions per day) (62 FR 28234 at

28240). The agency asked for comments on whether this approach for

establishing a qualifying soluble fiber level for psyllium husk-

containing products is appropriate or for data to support another

qualifying level for psyllium husk.

1. Qualifying Criteria for Psyllium Seed Husks

(Comment 9)

Some comments stated that it is premature to authorize this health

claim because of the limited data regarding an appropriate dose-

response curve. One comment stated that the qualifying level for

psyllium should be based on an intake level that will elicit a

clinically significant 5 percent reduction in blood cholesterol. The

comment stated that results from dose-response and meta-analysis

studies would assuage concerns that the proposed qualifying level of

soluble fiber from psyllium seed husk may not be an effective

cholesterol-lowering dose. Other comments agreed with the proposed

qualifying level for psyllium-containing foods. One comment stated that

the revised report of the dose-response study by Davidson et al. (Ref.

14), that was submitted with the comment, supports the effectiveness of

10.2 g psyllium husk daily intake in significantly lowering cholesterol

levels. In an analysis of data from subjects who completed the protocol

(197 of 286 subjects), LDL-cholesterol levels of the group with 10.2 g

psyllium husk daily intake was reported to be 5 percent lower than the

control group after 24 weeks. The comment also stated that the data

from the meta-analysis by Olson et al. (Ref. 34), which was submitted

with the comment, lends additional support to the conclusion that 10.2

g/d of psyllium is an appropriate level on which to base the qualifying

criteria for this claim. One comment stated that the maximum level of

daily psyllium husk consumption should be determined as part of the

generally recognized as safe (GRAS) process.

FDA notes that dose-response data are not a requirement to

establish the qualifying criteria for a substance that is the subject

of a health claim. Under Sec. 101.70, which describes the requirements

for health claim petitions, the petition must address whether there is

an optimum level of the particular substance to be consumed beyond

which no benefit would be expected (Sec. 101.70(f)B.1.). This

information may or may not be based on dose-response data. Even though

the optimal or lowest effective cholesterol lowering doses can not be

determined from the available data, the qualifying level (10.2 g/d of

psyllium husk) has been demonstrated to be effective. The results of

studies that evaluated the effect of psyllium husk intakes above 10.2

g/d showed no additional benefit on serum lipid levels (Ref. 7).

Therefore, the agency disagrees with the comments stating that dose-

response data are needed before the agency can authorize a health

claim. The totality of scientific data, which establish a significant

reduction in blood cholesterol based on an intake of 10.2 g/d of

psyllium seed husk, provides an adequate basis for establishing a

qualifying soluble fiber level for psyllium seed husk-containing

products.

Similarly, there is no basis to require that the qualifying

criteria for a substance associated with risk of CHD be based on the

amount of that substance to elicit a 5 percent reduction in blood

total- and LDL-cholesterol levels. The data on psyllium seed husk

suggests that the magnitude of the effect on blood lipids for intakes

of about 10 g/d of psyllium seed husk ranges from 4 to 6 percent for

blood total-cholesterol and about 4 to 8 percent for LDL-cholesterol

levels in conjunction with diets low in saturated fat and cholesterol

(Ref. 7). Although modest in size, these are clinically significant

reductions in blood lipids that translate to a reduced risk of CHD for

individuals with hypercholesterolemia and serve as a useful adjunct to

a diet already low in saturated fat and cholesterol.

In the absence of data to the contrary, the agency concludes that

based on the evidence submitted in comments and on the totality of

scientific data considered in its review of the petition, a daily

intake of 7 g of soluble fiber from psyllium seed husk (10.2 g of

psyllium seed husk) as part of a diet low in saturated fat and

cholesterol may reduce the risk of CHD by lowering blood total- and

LDL-cholesterol levels in individuals with mild to moderate

hypercholesterolemia.

FDA finds that the comment that a maximum level of daily

consumption of psyllium husk should be determined as part of the

psyllium husk GRAS status is not relevant to this rulemaking.

2. Issues Relative to Four Eating Occasions Per Day

(Comment 10)

The proposed qualifying level of soluble fiber from psyllium husk

was based on the assumption that individuals will consume four servings

of psyllium husk-containing foods a day. Some comments questioned

whether it is realistic to assume that consumers will consume four

servings per day of psyllium husk-containing foods. One comment stated

that the majority of Americans never consume any psyllium husk-

containing foods and that there is no evidence that a health claim

would convince them to consume up to four servings of these foods

daily. Other comments stated that the proposed rule would provide

consumers

[[Page 8110]]

with an increased selection of foods containing soluble fiber in

sufficient quantities to have a potentially beneficial influence on CHD

risk and thus have a positive public health impact.

FDA acknowledges that foods containing psyllium seed husk are not

widely available; e.g., the petitioner currently produces only one

product, a breakfast cereal, containing psyllium. However, the agency

disagrees with the comments that it is unrealistic to consider that

consumers could consume psyllium-containing foods four times a day. Two

studies (Refs. 8 and 14) that were reviewed by the agency tested

psyllium seed husk incorporated into a variety of foods that were

consumed during the day. These products included cereal, fruit drinks,

peanut butter, cookies, muffins, bread, pasta, and snack bars. In

addition to these products, the petitioner identified other food

products in which psyllium could be used, such as toaster pastries,

rolls, biscuits, tortillas, waffles, pancakes, pizza crust, stuffing,

breakfast bars, and a variety of ready-to-eat cereals (Ref. 35, pp. 90

and 91). Authorization of a claim on soluble fiber from psyllium seed

husk will be an incentive for manufacturers to expand product lines to

provide consumers with additional soluble fiber-containing products

that can be part of a heart healthy diet. Based on these facts, the

agency finds that a factual predicate exists to support the contention

that psyllium husk-containing foods could be consumed at four eating

occasions a day and, therefore, finds that the comments that questioned

whether such consumption was realistic are without support.

The agency notes that the approach used to determine the qualifying

level of soluble fiber from psyllium husk (i.e., dividing the amount

shown to provide a significant reduction in blood lipid levels by 4

eating occasions per day) is consistent with that used to determine the

qualifying level of -glucan soluble fiber from whole oats in

the soluble fiber from whole oats final rule. In that document, the

agency pointed out that the approach used to derive the qualifying

level of soluble fiber from whole oats is somewhat different from that

used in authorizing other health claims. It stated:

Specifically, the guiding principle for other health claims is

to use the established definition for ``good source'' or ``high''

which characterizes the amount of a nutrient, based on a percentage

of the Daily Value (DV) for the nutrient, in a serving of food. In

this way, products that qualify to bear the claim contain a

meaningful level of the substance per serving compared to the

recommended intake of the substance from all food sources. In the

case of this final rule, there is no DV for -glucan soluble

fiber or soluble fiber.

(62 FR 3584 at 3592).

The agency had also indicated in the soluble fiber from whole oat final

rule that it intends to propose to establish a Daily Reference Value

(DRV) for soluble fiber (62 FR 3584 at 3588). The establishment of a

DRV for soluble fiber would not only permit claims for ``good source''

and ``high'' in soluble fiber, but would allow the agency to consider

amendments to Sec. 101.81 to establish a single qualifying level for

soluble fiber from all eligible soluble fiber sources that would be

effective in lowering cholesterol. Available scientific evidence

suggests that there are a variety of soluble fibers in foods that may

demonstrate the benefit. Thus, smaller dietary contributions from any

one source could be appropriate given the potential for multiple

sources of such fibers.

A DRV for soluble fiber would establish a qualifying level for

soluble fiber blends in a food that would be effective in lowering

cholesterol in hypercholesterolemic individuals. However, in the

absence of a DRV for soluble fiber, the qualifying criteria for the

eligible sources of soluble fiber in this health claim must be based on

the scientific evidence specific for each soluble fiber source. The

agency intends to amend Sec. 101.81 to revise the qualifying levels of

soluble fibers when a DRV for soluble dietary fiber has been

established.

The agency notes that existing Sec. 101.81(d)(6) provides for an

optional statement informing consumers of the level of daily intake of

-glucan from whole oats that may help reduce the risk of CHD

and the contribution that one serving of the product makes to this

specified intake level. However, when issuing the soluble fiber from

whole oats and reduced risk of CHD health claim, FDA inadvertently

overlooked the requirement in Sec. 101.14(d)(2)(vii) of the general

requirements for health claims. That section states that if the claim

is about the effects of consuming the substance at other than decreased

levels, and if no definition for ``high'' has been established (e.g.,

where the claim pertains to a food either as a whole food or as an

ingredient in another food), the claim must specify the daily dietary

intake necessary to achieve the claimed effect, as established in the

regulation authorizing the claim.

As stated, FDA has not established a DRV for soluble fiber. As a

result, the term ``high'' is not defined for soluble fiber. Therefore,

consistent with Sec. 101.14(d)(2)(vii), a claim for soluble fiber from

whole oats requires specification of the daily dietary intake from

whole oats (3 g or more per day of -glucan soluble fiber from

whole oats) necessary to achieve a reduction in the risk of CHD. This

requirement is independent of the optional statement provided in

Sec. 101.81(d)(6).

When discussing the optional statement under Sec. 101.81(d)(6) in

the soluble fiber from whole oats final rule, FDA stated that when the

amount of soluble fiber to be consumed per day is stated, the amount

per serving is also needed so that consumers would not be misled to

believe that a serving of the food contributes the full daily amount

(62 FR 3584 at 3596). Therefore, to be consistent with the current

regulation in Sec. 101.14(d)(2)(vii) and with the need to specify the

amount of soluble fiber that a serving of food contributes when the

daily dietary intake is specified in the claim, the agency is

requiring, under Sec. 101.81(c)(2)(i)(G), that this information be

included in a health claim for both whole oats and psyllium husk

soluble fiber claims. However, because FDA did not note this

requirement in the soluble fiber from whole oats final rule, firms

currently marketing foods that bear the health claim for whole oats may

wait until the next printing of their food labels and labeling for such

foods to incorporate this added information.

Therefore, the agency is adding Sec. 101.81(c)(2)(i)(G) in this

final rule to clarify current regulatory requirements. Existing

Sec. 101.81(d)(6), which provides for the same information for whole

oats as an optional statement, is being removed. Accordingly,

Sec. 101.81(c)(2)(i)(G) states that the claim shall specify that an

intake of 7 g or more per day of soluble fiber from psyllium seed husk,

or an intake of 3 g or more per day of -glucan soluble fiber

from whole oats may help reduce the risk of CHD. Such a claim must be

accompanied by information on the contribution that one serving of the

product makes to the specified daily dietary intake level. Any foods

containing psyllium seed husk, or whole oats, and bearing the health

claim are required to include this information as part of the claim.

3. Blends of Eligible Soluble Fibers

In the psyllium husk proposed rule, the agency noted that foods

might be produced with a blend of the eligible soluble fibers listed in

Sec. 101.81(c)(2)(ii) and stated that it would be willing to consider

whether such foods should be eligible to bear the health claim (62 FR

28234 at 28240). However, the agency stated that it does not have the

data from which to evaluate the relationship between consumption of

foods

[[Page 8111]]

containing both psyllium and whole oats and risk of heart disease, and

cannot assume that foods containing a blend of these grains would have

the same ability to affect blood total- and LDL-cholesterol levels when

compared to a product containing either whole oats or psyllium. In the

proposal, the agency encouraged manufacturers to petition to amend

Sec. 101.81 further if it can be demonstrated that a diet that is low

in saturated fat and cholesterol that includes a blend of the eligible

soluble fibers listed in Sec. 101.81(c)(2)(ii) has an effect on the

risk of heart disease.

(Comment 11)

One comment agreed with the agency's tentative conclusion not to

include blends of the eligible soluble fibers at this time. The comment

stated that data should be submitted to verify the effectiveness of any

soluble fiber blend.

The agency agrees that data are needed to verify the effectiveness

of blends of soluble fiber. In the absence of a review of such data,

FDA is not including the option of a blend of the eligible soluble

fibers listed in Sec. 101.81(c)(2)(ii) in this final rule. While some

studies submitted to the agency did evaluate the usefulness of soluble

fiber mixtures in lowering blood cholesterol levels, they were outside

the scope of this rulemaking, which pertains to the effects of soluble

fiber from psyllium alone. As a result, time and resource constraints

did not allow for an indepth review of how blends of eligible soluble

fibers might work in synergy with one another. Such a task would better

be addressed as a part of rulemaking to establish a DRV for soluble

fiber and a review of qualifying levels.

F. Soluble Fiber From Certain Foods and From Eligible Food Sources

In the psyllium husk proposed rule, the agency proposed to modify

the section heading of Sec. 101.81 from ``Soluble fiber from whole oats

and risk of coronary heart disease'' to ``Soluble fiber from certain

foods and risk of coronary heart disease'' (62 FR 28234 at 28241). The

agency stated that:

``soluble fiber from certain foods'' reflects the fact that the

subject of the claim is no longer a specific source of soluble

fiber, i.e., beta-glucan from whole oats, but rather a broader class

of substances that includes those sources of soluble fiber for which

there is significant scientific agreement that they may help to

reduce the risk of heart disease.

(62 FR 28234 at 28241).

The agency also proposed to revise the statement ``soluble fiber from

whole oats'' in Sec. 101.81(a), (a)(3), (b), (b)(2), (c)(2)(i),

(c)(2)(i)(A), (d)(3), and (e) to state ``soluble fiber from certain

foods,'' and in Sec. 101.81(c)(2)(i)(E), (c)(2)(i)(F), and (d)(2) to

read ``soluble fiber from the eligible food sources from paragraph

(c)(2)(ii) of this section'' (62 FR 28234 at 28241).

(Comment 12)

The agency received one comment that raised issues relative to the

agency's decision to modify the soluble fiber from whole oats and CHD

rule to a claim on soluble fiber from certain foods. This comment

argued that the final rule for Sec. 101.81 inappropriately refocused

this claim from ``whole oats'' to ``soluble fiber from whole oats'' and

heart disease. The comment asserted that -glucan was included

in the whole oats proposed rule only as a quantitative measure of whole

oats for compliance purposes. This comment further argued that because

the eligible source of -glucan soluble fiber is whole oat

products whereas the eligible source of psyllium soluble fiber is an

isolated fiber-rich fraction (e.g., husk) separated from the whole

psyllium seed, these substances should not be combined in one

regulation.

The agency disagrees that the focus of Sec. 101.81 should be whole

oats. The rationale for positioning this claim as a soluble fiber claim

was explained in the soluble fiber from whole oats final rule (62 FR

3584 at 3585).

G. Issues Relative to the Safety of Psyllium Seed Husk

Prior to submitting the health claim petition, the petitioner had

petitioned FDA to affirm that the use of psyllium seed husk in grain-

based foods is GRAS (55 FR 4481, February 8, 1990). In the psyllium

husk proposed rule, the agency noted that although FDA has reached no

decision on the GRAS affirmation for the use of this substance, the

petition appears to contain evidence that the use of psyllium seed husk

at levels necessary to justify a claim is safe and lawful, as required

by Sec. 101.14(b)(3)(ii) (62 FR 28234 at 28236). However, the agency

indicated that there are some public safety concerns with the

consumption of psyllium seed husk (e.g., colonic epithelial cell

proliferation, allergenicity, and gastrointestinal obstruction). The

agency asked for comments on whether these concerns would be a basis

for not authorizing the proposed health claim. The agency also

recognized that an increase in psyllium consumption is likely if the

proposed health claim is authorized (62 FR 28234 at 28236). Therefore,

the agency asked for comments on what type of actions may be necessary

to ensure that long-term consumption of psyllium seed husk will be at

safe levels, e.g., limiting psyllium husk content of foods or the kinds

of foods that can bear a claim.

1. Restrictions on Psyllium Husk Content of Foods or on Types of Foods

That Can Bear a Claim.

(Comment 13)

FDA received several comments regarding the safety of psyllium

husk-containing foods. Some comments stated that psyllium husk has a

long history of safe human consumption as a laxative product at the

intake level upon which the qualifying food level of psyllium husk is

based. Furthermore, the comments noted that prior authoritative reviews

of the safety of psyllium husk in food, such as the 1993 LSRO

evaluation of the safety of psyllium seed husk as a food ingredient

(Ref. 39), concluded that there were no grounds to suggest that

consumption of as much as 25 g/d of psyllium husk would be a hazard to

the public. These comments argued that therefore it is unnecessary for

FDA to restrict the types of psyllium husk-containing food products,

the amount of psyllium husk that may be in a food product, or the

amount of psyllium husk that should be consumed per day as conditions

for use of the soluble fiber from psyllium husk health claim. Other

comments asserted that there is inadequate information about limits of

how much psyllium husk can be incorporated into foods, or about safe

levels of intake for long-term consumption. These comments argued that

there should be limits placed on permissible levels of psyllium husk in

foods and types of foods to which psyllium husk may be added. One

comment suggested that psyllium husk-containing foods be required to

bear a label statement warning consumers of the maximum amount of

psyllium husk that should be consumed per day.

FDA agrees that there is a history of human oral consumption of

psyllium husk, both in food and over-the-counter (OTC) products, at the

daily intake level contemplated for this health claim. The daily intake

of psyllium husk that FDA has concluded is effective in reducing CHD

risk (10.2 g psyllium husk, which is the amount of psyllium husk that

is necessary to provide 7 g of soluble fiber) is well below the daily

intake level that the 1993 LSRO psyllium husk report (Ref. 39)

concluded was safe (i.e., 25 g psyllium husk). FDA does not expect

authorization of the health claim to result in potential psyllium husk

consumption exceeding this safe level.

The 1993 LSRO report based its calculation of the potential daily

intake of psyllium husk, for a consumer preferentially selecting

products containing psyllium husk, on the

[[Page 8112]]

selection of four servings of psyllium husk-containing foods per day.

FDA considers four servings per day to be a reasonable estimate of

consumption for several reasons.

First, consumers who are looking for foods that are identified as

useful in reducing risk of CHD need not seek only psyllium-husk

containing foods. They will also be able to select from foods that use

the health claims approved for foods low in saturated fat and

cholesterol (Sec. 101.75 (21 CFR 101.75)); for fruits, vegetables, and

grain products that contain fiber, particularly soluble fiber

(Sec. 101.77); and for foods containing soluble fiber from whole oats

(Sec. 101.81).

Second, many types of frequently-consumed foods will not offer

psyllium husk-containing alternatives. For example, foods such as raw

meat, fish, and poultry; eggs; fats and oils; nuts and seeds; and raw

fruits and vegetables are not suitable candidates for the addition of

psyllium husk. In addition, technological or organoleptic effects of

the use of psyllium husk at levels needed to make a health claim will

limit its use in other categories of foods.

Third, because the subject health claim is only allowed on foods

that are low in fat, saturated fat, and cholesterol, not all foods to

which psyllium husk could be feasibly be added would be eligible to

bear a health claim. Thus, there would be no incentive for a

manufacturer to add psyllium husk to such foods, other than at the

small amounts that may be used for technological purposes (e.g.,

emulsifiers or binders).

Lastly, most of the new psyllium husk-containing foods that are

expected to be developed are grain-based and as such are often used as

alternates for one another in usual dietary patterns (e.g., cereals,

breakfast bars, toaster pastries, rolls, biscuits, pancakes, or waffles

served at breakfast).

For the mentioned reasons, FDA, in evaluating this health claim,

considers the selection of four servings of psyllium husk-containing

foods per day to be a reasonable expectation of consumption when

considering the possible use of psyllium husk in all food categories.

Estimation of the potential daily intake of psyllium husk is also

dependent upon the amount of the ingredient in each food. In the 1993

LSRO report, maximum levels of use were reported as designated by the

Kellogg Co. at 7.5 percent by weight for bread-based products (e.g.,

bread, rolls, muffins, doughnuts, biscuits, tortillas, waffles,

pancakes, pizza crust and stuffing), pasta, and toaster pastries. In

addition, the maximum levels of use were reported to be 10 percent by

weight for breakfast bars, and 15 percent by weight for ready-to-eat

cereals (Ref. 39). Assuming the highest maximum level of use, 15

percent in ready-to-eat cereals, the consumption of four 30 g servings

(i.e., the reference amount customarily consumed for high fiber cereals

(Sec. 101.12(b) Table 2)) would result in a daily intake of 18 g (30 g

multiplied by 15 percent = 4.5 g/serving, multiply by 4 servings = 18

g/d). Moreover, any technological uses of psyllium husk in foods are at

such low levels (e.g., 0.5 percent in frozen desserts) that they are

not likely to have a notable impact on total daily intake.

A total daily intake of 18 g is within the range of intakes

considered safe in the 1993 LSRO report (i.e., up to 25 g/d) (Ref. 39).

However, FDA expects that actual consumption will be less than this

amount because the maximum use levels were designated prior to the

agency's establishment of the health claim qualifying level. FDA

expects that manufacturers who develop new psyllium husk-containing

foods would do so to make use of the health claim. As such, the health

claim qualifying level (i.e., 2.6 g per reference amount) would be a

major factor in determining the amount of psyllium husk to include in

new psyllium husk-containing foods.

Based on these considerations, the agency disagrees with the

comments that argued that limits should be placed on permissible levels

of psyllium husk in foods or on the types of foods to which psyllium

husk may be added. Therefore, no changes are being made to

Sec. 101.81(c)(iii)(A)(2) that describes the nature of the food.

As noted in the psyllium husk proposed rule (62 FR 28234 at 28235),

a preliminary review of the petitioner's GRAS affirmation petition

revealed that it contains significant evidence supporting the safety of

the consumption of up to 25 g/d of psyllium husk in a variety of food

categories (i.e., types of foods). This amount is well in excess of the

levels necessary to justify a health claim (i.e., 10.2 g/d) and the

amounts that would reasonably be expected to be consumed in a day.

Accordingly, based on the totality of the evidence, FDA is not at this

time taking issue with the petitioner's view that the use of psyllium

husk is safe and lawful. Therefore, the agency concludes that the

petitioner has provided evidence that satisfies the requirements in

Sec. 101.14(b)(3)(ii) that psyllium seed husk at the levels necessary

to justify a claim is safe and lawful.

(Comment 14)

Several comments discussed evidence from animal studies suggesting

that the relationship between effects of dietary fiber on rodent

colonic mucosal proliferation and the development of neoplasia is

unclear. These comments stated that colonic epithelial cell

proliferation is not a significant issue relative to the safety of

psyllium seed husk as there is no consensus as to whether epithelial

cell proliferation in rodent colonic mucosa is relevant to risk of

colon cancer. Some comments noted that colonic epithelial cell

proliferation is an issue of concern that needs additional research.

The agency agrees that colonic epithelial proliferation is not

sufficiently validated as a reliable endpoint for prediction of colon

tumorigenesis. While the rate of epithelial cell proliferation in the

rodent gastrointestinal tract has been reported to be increased by some

soluble dietary fibers and decreased by some insoluble dietary fibers,

there is no evidence upon which to conclude that the influence of

dietary fiber on the rate of epithelial proliferation is either adverse

or beneficial. Whether psyllium husk influences colonic epithelial cell

proliferation in humans as it does in rodents is unknown. Although

enhanced cellular proliferation is associated with the neoplastic

process, proliferation rates have been reported to be variably

influenced by a number of dietary constituents and other exogenous and

endogenous factors, and a significant overlap in proliferation rates

between subjects at high and low risk of colon cancer has been observed

(Ref. 40). Therefore, the agency concludes that the issue of epithelial

cell proliferation is not a basis on which to deny this health claim.

2. Allergic Potential of Psyllium Husk

In the psyllium husk proposed rule, the agency acknowledged reports

of allergic reactions from consumption of psyllium husk-containing

food. The majority of these reports involved ingestion of a cereal made

with psyllium husk of less than 95 percent

[[Page 8113]]

purity. Because information provided by the petitioner suggested that

the purity of the psyllium husk is inversely related to its

allergenicity, FDA proposed a purity criterion for psyllium husk to be

eligible for the claim. Under comment 8 in section II.D.1 of this

document, the agency stated that psyllium husk purity specifications of

proposed Sec. 101.81(c)(2)(ii)(B)(1) are being adopted in the final

rule.

(Comment 15)

Two comments stated that the declaration of an ingredient in the

ingredient list of the food label is sufficient labeling to alert

consumers to the presence of allergenic components in foods and that

additional labeling is unnecessary. Other comments stated that in

consideration of the allergic potential of psyllium, the presence of

psyllium husk in a food should be declared on the principal display

panel in addition to the ingredient declaration.

Some comments agreed with the proposed husk purity specifications

as an adequate means of reducing the potential for allergic responses.

One comment explained that the major source of allergenic proteins in

psyllium seed husk is from residual portions of the whole seed. The

comment stated that the removal of the inner seed portions leaves a

very low level of residual protein in 95 percent purity psyllium husk

and thus, the potential for serious allergic reactions would be rare.

However, the comment also suggested that a label statement with an

appropriate caution as to the risk for allergic reactions would provide

added assurances for consumers. Still other comments argued that the

proposed purity standards for psyllium seed husk will not eliminate the

risk for allergic reactions to psyllium husk-containing foods and as

such, a cautionary statement alerting consumers to the risk of allergic

reactions should be required labeling. None of the comments provided

data.

The agency is not convinced by these comments that labeling, other

than declaration in the ingredient statement when psyllium husk is

added as a food ingredient, is necessary because of psyllium's allergic

potential. The agency recognizes the possibility of isolated cases of

allergic reactions to ingested allergenic substances in foods or food

components, including psyllium seed husk. However, the agency believes

that the declaration of the allergenic substance in the ingredient list

on the food label provides adequate information for consumers regarding

the presence of allergenic ingredients in food products. Psyllium seed

husk is required to be declared in the ingredient statement of a food

to which it is added. The agency has no basis for concluding that

additional labeling requirements for the use of this health claim would

have an impact on reducing the potential for allergic reactions from

consumption of psyllium husk-containing foods. The agency would not

object to any additional truthful, nonmisleading information regarding

allergenicity that a manufacturer may wish to include on the food

label.

3. Gastrointestinal Obstruction

In the psyllium proposed rule, the agency discussed the potential

for esophageal and gastrointestinal obstructions to occur following

consumption of psyllium seed husk when not consumed with sufficient

liquid (62 FR 28234 at 28236). The agency noted that the LSRO expert

panel (Ref. 39) reported that esophageal and gastrointestinal

obstruction due to psyllium seed husk was associated almost exclusively

with consumption without proper hydration of bulk-forming fiber

laxatives and not with consumption of psyllium-containing cereal

consumed with milk (62 FR 28234 at 28236). Comments were requested on

whether psyllium husk-containing foods should carry a statement

advising that the product be consumed with liquids, or whether the

potential for blockage is not an issue of concern for psyllium husk-

containing food (62 FR 28234 at 28236).

(Comment 16)

Several comments discussed the potential for esophageal and

gastrointestinal obstructions from consumption of psyllium husk without

sufficient liquid. These comments recommended that the agency adopt

labeling requirements for psyllium husk-containing foods advising

consumers to drink adequate fluids when consuming such foods. Some of

these comments suggested that such statements be similar to those

required under Sec. 201.319 (21 CFR 201.319) (Warning Statements

Required for Over-the-Counter Drugs Containing Water-Soluble Gums as

Active Ingredients (58 FR 45194, August 26, 1993)) for OTC products to

ensure consumers are aware of the consequences of inadequate hydration.

In general, these comments justified their recommendations on the basis

that authorization of the proposed health claim would encourage

incorporation of psyllium seed husk into additional types of foods, and

that these new food products containing significant amounts of psyllium

seed husk will not necessarily be intended to be consumed with liquids.

One comment asserted that a label statement advising the consumption of

the psyllium husk-containing food with liquids is unnecessary because

psyllium husk-containing foods would be consumed at meals when it is

likely that sufficient liquid would also be consumed. The comment

argued that the soluble fiber in psyllium husk-containing foods is

already hydrated, which would reduce its ability to swell in the

gastrointestinal tract. This comment further noted that the 1993 LSRO

report on the safety of using psyllium seed husk as a food ingredient

(Ref. 39) found no safety issues in this regard. None of the comments

provided data.

The agency agrees with comments suggesting that authorization of a

claim for soluble fiber from psyllium husk and risk of CHD may lead to

an increase in the number and type of foods containing psyllium husk.

Moreover, the agency agrees that there are no assurances that new

psyllium husk-containing foods are likely to be consumed at meals or

with liquids. Foods such as cookies, breakfast bars, and toaster

pastries may be consumed as snacks at times when a liquid is not

consumed. Psyllium husk could also be incorporated into dietary

supplement products that may be consumed apart from meals. The comment

that stated that the psyllium seed husk in foods is already hydrated,

which would affect its ability to swell in the gastrointestinal tract,

provided no data to document or with which to evaluate differences in

the swell volume and rate of swelling of different psyllium husk-

containing foods.

The LSRO expert panel that considered the safety of psyllium seed

husk used as a food ingredient (Ref. 39) concluded that the moderate

amounts of psyllium seed husk that are likely to be used in toaster

pastries, bread-based products, breakfast bars, pasta, and cereals

would not be expected to cause gastrointestinal obstruction. However,

this panel further concluded that the possibility of obstruction would

be reduced by suitable suggestions that these products be consumed with

fluids.

The agency addressed the risk of esophageal obstruction by water

soluble gums (including psyllium husk) in an advance notice of proposed

rulemaking to establish a monograph for OTC laxative, antidiarrheal,

emetic, and antiemetic drug products (40 FR 12902, March 21, 1975). The

agency discussed in the final rule the evidence of at least 191 cases

of esophageal obstruction and 8 cases of asphyxia, resulting in 18

deaths, associated with orally-administered OTC laxative and weight

control products containing a variety of

[[Page 8114]]

water soluble gums (58 FR 45194 at 45195). The agency concluded that

there is a risk that these types of products will swell to form a

viscous adhesive mass (i.e., viscous gel) that can block the throat or

esophagus. Because of this risk, the agency requires warning and

direction statements for OTC drug products containing water soluble

gums, including psyllium husk, as active ingredients when these

products are marketed in a dry or partially hydrated form

(Sec. 201.319). Fully hydrated water soluble gums were acknowledged to

not pose any significant risk of causing esophageal obstruction (58 FR

45194 at 45196).

In the final rule on ``Warning Statements Required for OTC Products

Containing Water-Soluble Gums as Active Ingredients,'' the agency

stated that it will continue to evaluate the use of water-soluble gums

in any product marketed for human consumption, food or drug, and

appropriate warnings will be proposed if a need to do so is found (58

FR 45194 at 45196).

The agency anticipates that authorization of a health claim for

soluble fiber from psyllium husk may result in an increase of both the

type and number of foods containing psyllium husk, and that foods

eligible to bear the psyllium husk health claim will contain amounts of

psyllium husk comparable to that commonly found in OTC laxative drugs.

However, the agency recognizes that there are inherent differences

between foods in conventional food form, which contain other food

ingredients such as salt, sugar, and flour in addition to psyllium

husk, and OTC drug products that would influence the likelihood of

esophageal obstruction occurring from the ingestion of psyllium husk-

containing foods. For example, drug products are formulated in tablets,

capsules, and powders that are usually intended to be ingested and

swallowed as a single bolus, whereas a serving of food is not swallowed

as a single bolus, but eaten in several bites, chewed, and swallowed

over a period of time. Psyllium husk-containing conventional foods also

differ from drug products in that the psyllium husk in a food in

conventional food form is dispersed within a larger volume of other

food components (e.g., sugars, salt, wheat flour, egg). Dispersion in

other ingredients prevents the soluble fiber of psyllium husk from

physically associating to form a gel network (i.e., a viscous adhesive

mass) (Refs. 41 and 42). Because a strong gel network is not formed due

to the presence of these other ingredients, the food product will swell

and thicken in a similar fashion to other high fiber foods (e.g.,

ready-to-eat cereals), without forming a viscous mass capable of

causing obstruction (Ref. 42). The agency believes that, because the

composition and manner of consumption of psyllium husk-containing

conventional foods, unlike OTC products, inhibit the formation of a

viscous gel in the esophagus, the label requirements for OTC drug

products may not be applicable to certain foods containing psyllium

husk that bear a health claim.

Section 201(n) of the act (21 U.S.C. 321(n)) states that, in

determining whether labeling is misleading, the agency shall take into

account not only representations made about the product, but also the

extent to which the labeling fails to reveal facts material in light of

such representations made or suggested in the labeling or material with

respect to consequences which may result from use of the article to

which the labeling relates under the conditions of use as are customary

or usual (see 21 CFR 1.21). Thus, the omission of certain material

facts from the label or labeling on a food causes the product to be

misbranded within the meaning of sections 403(a)(1) and 201(m) of the

act (21 U.S.C. 343(a)(1)).

As discussed out in the final rule on warning statements for OTC

products (58 FR 45194), esophageal obstruction and asphyxiation are

potential health risks associated with the oral consumption of dry or

incompletely hydrated psyllium husk when these products are ingested

without adequate fluid or when they are used by individuals with

esophageal narrowing or dysfunction, or with difficulty swallowing.

There is the possibility that esophageal obstruction and choking from

ingestion of psyllium husk-containing food would be a consequence of

extending the food use of psyllium husk to certain types of food

products, such as those that are predominately composed of psyllium

husk. Therefore, FDA has determined that the potential for esophageal

blockage from not consuming adequate amounts of fluids when consuming

certain types of dry or incompletely hydrated psyllium husk-containing

food is a material fact.

The agency concludes that it would be misleading under section

201(n) of the act for certain foods to contain dry or incompletely

hydrated psyllium husk without a label statement relative to potential

risks and concerns for adequate fluid intake. Therefore, in this final

rule FDA is amending its regulations to require a statement

[hereinafter ``label statement''] to inform consumers of the potential

consequence if the psyllium husk-containing food is not consumed

appropriately, to inform consumers of the action necessary to avoid the

consequence, and to advise persons with swallowing difficulties to

avoid consumption of the product.

Because the concern for esophageal obstruction exists whether or

not the food bears a health claim, FDA is codifying the need for the

required label statement in Sec. 101.17 Food labeling warning and

notice statements (21 CFR 101.17) rather than in the health claim

regulation. The required label statement is also reflected in

Sec. 101.81(c)(1). Accordingly, FDA is adding paragraph (f)(1) to

Sec. 101.17 to specify that when dry or incompletely hydrated psyllium

husk is present in a food and the food bears a health claim, the label

must include a statement such as:

The food should be eaten with at least a full glass of liquid.

Eating this product without enough liquid may cause choking. Do not

eat this product if you have difficulty swallowing.

In the psyllium proposed rule, the agency had specifically

requested comments on whether psyllium husk-containing foods should

carry a statement advising that the product be consumed with liquids.

However, the agency had not suggested that it was considering requiring

labeling for all psyllium husk-containing foods regardless of whether

the food label bears a health claim statement. Therefore, FDA is not

attempting, in this final rule, to extend the required statement to

psyllium husk-containing foods not subject to this rulemaking, i.e.,

foods not bearing a health claim. Instead, the agency plans to propose,

in a separate rulemaking, that the required label statement be extended

to other psyllium husk-containing foods that do not bear a health

claim.

However, as discussed previously, the agency recognizes that there

are factors that suggest that the formation of a viscous adhesive mass,

which is associated with a risk of choking, does not result from

consumption of certain psyllium husk-containing foods that are in a

conventional food form. Therefore, the agency believes that certain dry

or incompletely hydrated conventional food products, i.e., those that

do not form a viscous adhesive mass under usual conditions of use,

would not require the label statement. The agency believes that an

exemption from the label statement should be available to firms when a

viscous adhesive mass is not formed when the product is exposed to

fluids so that the product poses no greater risk to the consumer than a

comparable product without psyllium husk. The agency does not currently

[[Page 8115]]

have data or information on which it could base such an exemption for

specific conventional food products. Moreover, because FDA, under

Sec. 101.70(j)(4)(i), is obligated to publish this final rule within

the time limitation established for issuing final rules for health

claim proceedings, the agency is unable, in this final rule, to specify

the conditions under which exemptions to the label statement for

certain conventional food products are warranted. Consequently, the

agency will provide firms that seek such an exemption with guidance as

to what would be necessary to demonstrate that such an exemption to the

label statement is warranted. The agency will further evaluate the need

for the label statement on specific types of psyllium husk-containing

foods that bear a health claim in the separate rulemaking that will

address the extension of the label statement to psyllium husk-

containing foods that do not bear a health claim. If the agency

challenges a firm's determination that its conventional food product is

entitled to the exemption in Sec. 101.17(f)(1), and as a result is not

misbranded within the meaning of section 201(n) of the act without such

label statement, the agency will evaluate the basis for the firm's

exemption on a case-by-case basis.

Section 403(f) of the act requires that mandatory label information

be prominently placed on the label with such conspicuousness (compared

with other words, statements, designs, or devices in the labeling) as

to render it likely to be read and understood by the ordinary

individual under customary conditions of use. FDA has generally

considered the label information panel to be the appropriate location

for notice and warning statements. As discussed in the agency's

rulemaking requiring warning statements on iron-containing dietary

supplements (62 FR 2218, January 15, 1997), consumer focus group

studies establish that a warning statement need not be placed on the

principal display panel (PDP) to be effective in informing consumers of

the hazard. Participants in the focus groups reasoned that the front of

the product package was used for marketing purposes and stated that

they were accustomed to looking at the ``back of products'' for

nutrition and factual information, including warning statements (Ref.

43). Consequently, in the case of iron-containing dietary supplements,

the agency required that the warning statement appear on the

information panel.

The agency believes that for the required label statements on

psyllium husk-containing products, the requirement for prominence and

conspicuousness would similarly be met if the statements appeared on

the information panel. However, the agency would not object to firms

placing the required statement on the PDP, because the PDP would

provide even greater prominence. Accordingly, FDA is requiring in

Sec. 101.17(f)(2) that the required statement for psyllium husk-

containing foods appear either on the product information panel or on

the PDP.

The requirement in the act for prominent display means that the

required label statement must appear in a manner that makes it readily

observable and likely to be read. The agency notes that 21 CFR 101.2(c)

requires that mandatory information appearing on the PDP and

information panel, including information required by Sec. 101.17,

appear prominently and conspicuously in a type size no less than one-

sixteenth inch.

In addition, current agency regulations that require a ``warning''

statement on the product label or in labeling (e.g., the statement

required by Sec. 101.17(e) on iron-containing dietary supplements in

solid oral dosage form) or a label ``notice'' statement (e.g., the

statement required by Sec. 101.17(d)(3) on protein products that are

not covered by the requirements of Sec. 101.17(d)(1) and (d)(2))

require that the identifying term ``WARNING'' or ``NOTICE'' be

capitalized and immediately precede the language of the applicable

labeling statement. Based on FDA's experience in rulemaking pertaining

to warning statements on protein products (47 FR 25379, June 11, 1982),

as the severity of the consequences lessens, the severity of the

warning may also lessen. Therefore, the agency considers the term

``NOTICE'' to be appropriate to alert consumers to the label statement.

Accordingly, the agency is requiring in Sec. 101.17(f)(2) that the

capitalized word ``NOTICE'' immediately precede the required elements

of the label statement.

4. Laxative effects

(Comment 17)

One comment noted that psyllium husk is primarily consumed for its

laxative effect. This comment asserted that the label and labeling of

psyllium husk-containing foods should inform consumers about the

adverse effects of consuming excess amounts of psyllium by including a

disclosure statement such as ``Consumption of psyllium in excess of --

-- mg may cause diarrhea.'' Other comments noted that intake of

psyllium-containing foods is self-limiting due to satiety and laxative

effects.

FDA disagrees that the possible effects on bowel function of

consuming 10 g/d of psyllium seed husk in foods would be considered as

causing diarrhea or an adverse health consequence. Diarrhea is

characterized by loose, watery bowel movements. The water-holding

capacity and bulking effect of undigested soluble fiber from psyllium

husk softens colonic contents and stimulates peristalsis, both of which

facilitate movement of the colonic contents. Ingestion of psyllium husk

does not lead to diarrhea. The expected effect of the use of bulk-

forming fiber laxatives is an increase in stool volume and frequency of

bowel movements. There is no reason to consider that a daily intake of

10 g of psyllium seed husk as a component of food would have any effect

on the bowel other than to promote normal functioning by softening

fecal contents and increasing fecal volume. Because the daily intake of

psyllium seed husk that is approved for this health claim is the same

customary daily intake when used as a laxative, amounts in excess of

that required for laxation are not needed to obtain potential benefits,

in reduced risk of CHD, from consumption of psyllium seed husk.

Moreover, consumption in excess of 10.2 g/d of psyllium seed husk would

not be expected to result in diarrhea because intake of psyllium husk

increases stool volume and frequency of bowel movements. Softening of

fecal contents is not diarrhea and does not represent an adverse health

effect as suggested by the comment. Therefore, the agency finds that

there is no basis on which to require, as suggested by the comment, a

warning statement to alert consumers about possible adverse effects

from consuming psyllium husk-containing foods.

H. General Health Claim Issues

1. Health claims for substances with OTC drug uses.

(Comment 18)

One comment stated that approving a claim on a product that

incorporates an OTC drug into a food would set a precedent for allowing

claims on ``functional foods,'' foods consumed primarily for their

purported ability to prevent or treat disease. The comment stated that

this was not the intent of Congress when it passed the 1990 amendments.

FDA notes that bran, as well as psyllium husk, are listed as

effective bulk-forming laxative active ingredients in the tentative

final monograph on laxative drug products for OTC human use (50 FR

2124, January 15, 1985) and that oat bran is also an eligible source of

soluble fiber from whole oats for this

[[Page 8116]]

health claim. The fact that a substance also has uses as an OTC drug

does not bear on its recognized status as a food. FDA notes that

psyllium seed husk is a recognized source of dietary fiber and an

established food ingredient. Therefore, the comment is not relevant to

this rulemaking.

2. Food-Specific Health Claims

(Comment 19)

Some comments stated that the proposed claim for a specific soluble

fiber should not be authorized because claims for specific foods create

the false impression that consumption of those foods is a more

important factor than is the overall diet in reduction of risk of CHD.

Other comments asserted that allowing health claims for individual

substances portrays specific foods as panaceas or functional foods and

undermines the purpose of the 1990 amendments. One comment expressed

concern that claims about individual sources of dietary fiber are

inconsistent with the important dietary guidance of choosing diets high

in fruits, vegetables, whole grain foods, and other good sources of

fiber. One comment stated that the proposed claim does not inform the

consumer that frequent, long-term consumption of soluble fiber from

psyllium husk is necessary to lower cholesterol levels.

FDA addressed the issue of the appropriate subject of health claims

in rulemaking leading to, and including, the January 6, 1993, final

rule on general requirements for health claims (see 56 FR 60537 at

60542, November 27, 1991; 58 FR 2478 at 2479, January 6, 1993). While

some comments to proposed rulemaking maintained that health claims

should only be permitted for nutrients listed in nutrition labeling,

others argued that Congress intended claims to be authorized for foods

as well as nutrients. Comments quoted private and public health

organizations' testimony before Congress that health claims should

reflect dietary recommendations about foods and ``should assist the

public to integrate specific food products into a well balanced diet''

(58 FR 2478 at 2479). After extensive discussion, final rules

implementing the 1990 amendments defined health claims as claims

characterizing the relationship of any substance to a disease or

health-related condition, and defined ``substance'' as a specific food

or component of food (Sec. 101.14(a)(1) and (a)(2)). This permitted

health claims to be established for both nutrients and foods.

In the soluble fiber from whole oats final rule, the agency

addressed comments that expressed concern that a claim on whole oat

foods would portray the specific food as a ``magic bullet'' in reducing

heart disease risk. This concern was ameliorated when the scientific

evidence supported changing the subject of the claim to soluble fiber

from whole oats. In addition, the importance of a total diet low in

saturated fat and cholesterol to the nutrient/disease relationship was

emphasized (62 FR 3584 at 3585 and 3590). FDA noted that diets low in

saturated fat and cholesterol are considered by expert groups to be the

most effective dietary means of reducing heart disease risk. The agency

stated that while soluble fiber from whole oats contributes to this

effect, its role is generally recognized as being of smaller magnitude

(62 FR 3584 at 3590 and 3594).

Likewise, the agency concludes that the concerns described

previously that were raised in comments to the psyllium husk proposed

rule are adequately addressed by the fact that a health claim on

psyllium-containing foods will be required to state the subject of the

claim as ``soluble fiber from psyllium husk'' and to describe the

nutrient/disease relationship in the context of a diet low in saturated

fat and cholesterol. The comment provided no evidence to suggest that

health claims about specific foods or food ingredients will not

encourage consumers to follow dietary recommendations to eat a varied

diet containing other foods that are also good sources of fiber.

FDA notes that the subject health claim, as is the case for all

authorized health claims, requires that the claim be stated in the

context of a daily diet. This is accomplished through specific

requirements describing the nature of the claim, i.e., the relationship

of the substance to the disease or health-related condition in

paragraph (c)(2)(i) of each health claim regulation. These requirements

are intended to show the nature of the relationship between the subject

of the claim and the disease or health condition and to prevent any

misunderstanding that health benefits will accrue from single or

infrequent consumption of the subject nutrient or adherence to the

suggested dietary regimen. Examples of such wording include

``throughout life'' in the calcium/osteoporosis claim (21 CFR 101.72),

``daily'' in the folate/neural tube defect claim (21 CFR 101.79),

``diets low in fat * * *'' in health claims pertaining to cancer (21

CFR 101.73, 101.76, and 101.78) and ``diets low in saturated fat and

cholesterol * * *'' in health claims pertaining to heart disease

(Secs. 101.75, 101.77, and 101.81). Therefore, the agency is making no

changes in response to this comment.

The preamble of the soluble fiber from whole oats health claim

final rule considered the impact of the health claim on consumer

perception of food label references to oats (62 FR 3584 at 3596). A

comment had suggested that as consumers become aware of the

relationship between soluble fiber from whole oats and reduced risk of

CHD, statements such as ``made with oat bran'' would be an implied

nutrient content or health claim. In response to this comment, FDA

stated that it did not have information from which to conclude that

terms such as ``oat bran,'' ``rolled oats,'' or ``whole oat flour'' are

always in a context that constitutes an implied nutrient content or

health claim, and as such FDA would continue its policy to evaluate the

context of label statements on a case-by-case basis (62 FR 3584 at

3597). The agency further noted that if experience with label

statements about oat ingredients or other information persuades FDA

that additional regulatory controls are needed, the agency can take

action to establish appropriate regulations. The agency does not have

reason at this time to change this policy.

III. Environmental Impact

The agency has previously considered the environmental effects of

this rule as announced in the psyllium husk proposed rule (62 FR

28234). The proposed rule incorrectly cited a claim of categorical

exclusion under previous 21 CFR 25.24(a)(11). The agency has

determined, based on information contained in an environmental

assessment prepared under previous 21 CFR 25.31a(b)(5), that this

action has no significant impact on the environment and that an

environmental impact statement is not required. No new information or

comments have been received that would affect this determination. The

agency's finding of no significant impact and the evidence supporting

that finding, contained in an environmental assessment, may be seen in

the Dockets Management Branch (address above) between 9 a.m. and 4

p.m., Monday through Friday.

IV. Analysis of Economic Impacts

A. Benefit-Cost Analysis

FDA has examined the impacts of the final rule under 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 the regulatory approach that maximizes net

benefits (including potential

[[Page 8117]]

economic, environmental, public health and safety effects; distributive

impacts; and equity). According to Executive Order 12866, a rule 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 rule is not a significant rule as defined by Executive

Order 12866.

In addition, FDA has determined that this rule does not constitute

a significant rule under the Unfunded Mandates Reform Act of 1995

requiring cost-benefit and other analyses. A significant rule is

defined in section 1531(a) as ``a Federal mandate that may result in

the expenditure by State, local, and tribal governments in the

aggregate, or by the private sector, of $100,000,000 (adjusted annually

for inflation) in any 1 year * * *.''

Finally, in accordance with the Small Business Regulatory

Enforcement Fairness Act, the administrator of the Office of

Information and Regulatory Affairs of the Office of Management and

Budget has determined that this final rule is not a major rule for the

purpose of Congressional review.

The authorization of health claims about the relationship between

soluble fiber from psyllium seed husk and CHD results in either costs

or benefits only to the extent that food manufacturers elect to take

advantage of the opportunity to use the claim. The authorization of the

health claim will not require that any labels be redesigned, or that

any product be reformulated. However, the labels of foods containing

whole oats and bearing the health claim will require revision to

specify the daily dietary intake of -glucan soluble fiber from

whole oats necessary to achieve the claim effect. Because FDA is

allowing firms to wait to incorporate this change with other regularly

scheduled changes, this provision will not result in additional costs.

This final health claim will allow manufacturers to highlight the

benefits of soluble fiber from psyllium seed husk in addition to other

eligible food sources of soluble fiber for which FDA has already

approved a health claim. The benefit of establishing this health claim

is to provide for new information in the market regarding the

relationship between soluble fiber from psyllium seed husk and risk of

heart disease and to provide consumers with the assurance that this

information is truthful, not misleading, and scientifically valid.

B. Small Entity Analysis

FDA has examined the impacts of the final rule under the Regulatory

Flexibility Act (5 U.S.C. 601-612). If a rule has a significant

economic impact on a substantial number of small entities, the

Regulatory Flexibility Act requires agencies to analyze regulatory

options that would minimize the economic impact of that rule on small

entities.

Small entities will incur costs only if they opt to take advantage

of the marketing opportunity presented by this regulation. FDA cannot

predict the number of small entities that will choose to use the claim.

However, no firm, including small entities, will choose to bear the

cost of redesigning labels unless they believe that the claim will

result in increased sales of their product. Therefore, this rule will

not result in either a decrease in revenues or a significant increase

in costs to any small entity. Accordingly, under the Regulatory

Flexibility Act, 5 U.S.C. 605(b), the agency certifies that this final

rule will not have a significant economic impact on a substantial

number of small entities.

V. Paperwork Reduction Act

In the psyllium proposal, FDA stated its tentative conclusion that

the proposed rule contained no information collection provisions

necessitating clearance by the Office of Management and Budget (OMB)

and asked for comments on whether the proposed rule imposed any

paperwork burden. No comments addressing the question of paperwork

burden were received. FDA has evaluated the final rule and concludes

that it contains no information collection provisions. Although the

final rule would amend Sec. 101.17 to require a label statement on

foods containing psyllium husk and bearing a health claim, FDA is

supplying the information that must be disclosed in the label

statement. Therefore, the label statement is a ``public disclosure of

information originally supplied by the Federal government to the

recipient for purpose of disclosure to the public'' (5 CFR 1320(c)(2));

as such, it is not a ``collection of information'' subject to OMB

review under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et

seq.).

VI. 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. Kellogg Co., Kellogg's Bran Buds Cereal with natural wheat

bran and psyllium (product packaging) Kellogg Co., Battle Creek, MI,

1997.

2. The U.S. Pharmacopeia (USP 23), The National Formulary (NF

18), United States Pharmacopeial Convention, Inc., Rockville, MD, p.

1341-1342, 1995.

3. DHHS, Public Health Service (PHS), ``The Surgeon General's

Report on Nutrition and Health,'' U.S. Government Printing Office,

Washington, DC, pp. 83-137, 1988.

4. Food and Nutrition Board, National Academy of Sciences,

``Diet and Health: Implications for Reducing Chronic Disease Risk,''

National Academy Press, Washington, DC, pp. 291-309 and 529-547,

1989.

5. LSRO, FASEB, ``Physiological Effects and Health Consequences

of Dietary Fiber,'' Bethesda, MD, 1987.

6. LSRO, FASEB, ``Evaluation of Publicly Available Scientific

Evidence Regarding Certain Nutrient-Disease Relationships: 6.

Dietary Fiber and Cardiovascular Disease,'' Bethesda, MD, 1991.

7. Saltsman, J., Memo to file with Table 1: ``Summary of

Clinical Trials: Psyllium and CHD,'' and Table 2: ``Psyllium and

CHD,'' Docket No. 96P-0338, Dockets Management Branch, January 28,

1997.

8. Abraham, Z. D. and T. Mehta, ``Three-Week Psyllium-Husk

Supplementation: Effect on Plasma Cholesterol Concentrations, Fecal

Steroid Excretion, and Carbohydrate Absorption in Men,'' American

Journal of Clinical Nutrition, 47:67-74, 1988.

9. Anderson, J. W., N. Zettwoch, T. Feldman, J. Tietyen-Clark,

P. Oeltgen, and C. W. Bishop, ``Cholesterol-Lowering Effects of

Psyllium Hydrophilic Mucilloid for Hypercholesterolemic Men,''

Archives of Internal Medicine, 148:292-296, 1988.

10. Anderson, J. W, T. L. Floore, P. B. Geil, D. S. O'Neal, and

T.K. Balm, ``Hypocholesterolemic Effects of Different Bulk-Forming

Hydrophilic Fibers as Adjuncts to Dietary Therapy in Mild to

Moderate Hypercholesterolemia,'' Archives of Internal Medicine,

151:1597-1602, 1991.

11. Anderson, J. W., S. Riddell-Mason, N. J. Gustafson, S. F.

Smith, and M. Mackey, ``Cholesterol Lowering Effects of Psyllium-

Enriched Cereal as an Adjunct to a Prudent Diet in the Treatment of

Mild to Moderate Hypercholesterolemia,'' American Journal of

Clinical Nutrition, 56:93-98, 1992.

12. Anderson, J. W., M. H. Davidson, L. Blonde, W. V. Brown, W.

J. Howard, H. Ginsberg, L. D. Allgood, and K. W. Weingand, ``Long-

Term Cholesterol-Lowering Effects of Psyllium as an Adjunct to Diet

Therapy in the Treatment of Hypercholesterolemia,'' Submitted to

Family Medicine.

13. Bell, L. P., K. Hectorne, H. Reynolds, T. K. Balm, and D. B.

Hunninghake, ``Cholesterol-lowering Effects of Psyllium Hydrophilic

Mucilloid--adjunct Therapy to a Prudent Diet for Patients With Mild

to Moderate Hypocholesterolemia,'' Journal of the American Medical

Association (JAMA), 261:3419-23, 1989.

14. Davidson, M. H., K. C. Maki, J. C. Kong, L. D. Dugan, S. A.

Torri, H. H. Hall, K. B.

[[Page 8118]]

Drennan, S. Anderson, V. Fulgoni, L. Saldanha, and B. Olson, ``Long-

Term Effects of Consuming Psyllium-Enriched Foods on Serum Lipids,''

accepted for publication in the American Journal of Clinical

Nutrition, 1997.

15. Everson, G. T., B. P. Daggy, C. McKinley, and J. A. Story,

``Effects of Psyllium Hydrophilic Mucilloid on LDL-Synthesis and

Bile Acid Synthesis in Hypercholesterolemic Men,'' Journal of Lipid

Research, 33:1183-1192, 1992.

16. Gelissen, I. C., B. Brodie, and M. A. Eastwood, ``Effect of

Plantago Ovata (Psyllium) Husk and Seeds on Sterol Metabolism:

Studies in Normal and Ileostomy Subjects,'' American Journal of

Clinical Nutrition, 59:395-400, 1994.

17. Keane, W. F., V. T. Miller, L. P. Bell, C. E. Halstenson, L.

D. Allgood, H. Tully, and J. C. LaRosa, ``Effect of Psyllium in

Conjunction With a Low-Fat Diet on Plasma Lipids in Elderly Patients

With Mild-to-Moderate Hypercholesterolemia,'' Unpublished, 1996.

18. Levin, E. G., V. T. Miller, R. A. Muesing, D. B. Stoy, T. K.

Balm, and J. C. LaRosa, ``Comparison of Psyllium Hydrophilic

Mucilloid and Cellulose as Adjuncts to a Prudent Diet in the

Treatment of Mild to Moderate Hypercholesterolemia,'' Archives of

Internal Medicine, 150:1822-1827, 1990.

19. Neal, G. W., and T. K. Balm, ``Synergistic Effects of

Psyllium in the Dietary Treatment of Hypercholesterolemia,''

Southern Medical Journal, 83:1131-1137, 1990.

20. Schectman, G., J. Hiatt, and A. Hartz, ``Evaluation of the

Effectiveness of Lipid-lowering Therapy (Bile Acid Sequestrants,

Niacin, Psyllium, and Lovastatin) for Treating Hypercholesterolemia

in Veterans,'' American Journal of Cardiology, 71:759-765, 1993.

21. Sprecher, D. L., B.V. Harris, A. C. Goldberg, E. C.

Anderson, L. M. Bayuk, B. S. Russell, D. S. Crone, C. Quinn, J.

Bateman, B. R. Kuzmak, and L. D. Allgood, ``Efficacy of Psyllium in

Reducing Serum Cholesterol Levels in Hypercholesterolemic Patients

on High- or Low-Fat Diets,'' Annals of Internal Medicine, 119:545-

554, 1993.

22. Stoy, D. B., J. C. LaRosa, B. K. Brewer, M. Mackey, and R.

A. Muesing, ``Cholesterol-lowering Effects of Ready-to-Eat Cereal

Containing Psyllium,'' Journal of the American Dietetic Association,

93:910-912, 1993.

23. Stoy, D. B., J. C. LaRosa, B. K. Brewer, L. G. Saldhanda,

and R. A. Muesing, ``Lipid Lowering Effects of Ready-to-Eat Cereal

Containing Psyllium: a Randomized Crossover Trial,'' Unpublished,

1993.

24. Summerbell, C. D., P. Manley, D. Barnes, and A. Leeds, ``The

effects of Psyllium on Blood Lipids in Hypercholesterolaemic

Subjects,'' Journal of Human Nutrition and Dietetics, 7:147-151,

1994.

25. Weingand, K. W., N-A. Le, B. R. Kuzmak, W. V. Brown, B. P.

Daggy, T. A. Miettinen, B. V. Howard, and W. J. Howard, ``Effects of

Psyllium on Cholesterol and Low-Density Lipoprotein Metabolism in

Subjects With Hypercholesterolemia,'' Endocrinology and Metabolism,

4:141-150, 1997.

26. Gupta, R. R., C. G. Agrawal, G. P. Singh, and A. Ghatak,

``Lipid-lowering Efficacy of Psyllium Hydrophilic Mucilloid in Non-

insulin Dependent Diabetes Mellitus With Hyperlipidaemia,'' Indian

Journal of Medical Research, 100:237-241, 1994.

27. Stewart, R. B., W. E. Hale, M. T. Moore, F. E. May, and R.

G. Marks, ``Effect of Psyllium Hydrophilic Mucilloid on Serum

Cholesterol in the Elderly,'' Digestive Diseases and Sciences, 36:

329-334, 1991.

28. Jenkins, D., T. M. S. Wolever, E. Vidgon, C. W. C. Kendall,

T. P. P. Ransom, et al., ``Effect of Psyllium in

Hypercholesterolemia at Two Monounsaturated Fatty Acid Intakes,''

American Journal of Clinical Nutrition, 65:1524-1533, 1997.

29. Arjmandi, B. H., E. Sohn, S. Juma, S. R. Murphy, and B. P.

Daggy, ``Native and Partially Hydrolyzed Psyllium Have Comparable

Effects on Cholesterol Metabolism in Rats,'' Journal of Nutrition,

127:463-469, 1997.

30. Daggy, B. P., N. C. O'Connell, G. R. Jerdack, B. A. Stinson,

and K. D. R. Setchell, ``Additive Hypocholesterolemic Effect of

Psyllium and Cholestyramine in the Hamster: Influence of Fecal

Sterol and Bile Acid Profiles,'' Journal of Lipid Research, 38:491-

502, 1997.

31. Fernandez, M. L., M. Vergara-Jiminez, K. Conde, T. Behr, and

G. Abdel-Fattah, ``Regulation of Apolipoprotein B-Containing

Lipoproteins by Dietary Soluble Fiber in Guinea Pigs,'' American

Journal of Clinical Nutrition, 65:814-822, 1997.

32. Ganji, V., and C. V. Kies, ``Psyllium Husk Fiber

Supplementation to the Diets Rich in Soybean or Coconut Oil:

Hypocholesterolemic Effect in Healthy Humans,'' International

Journal of Food Science and Nutrition, 47:103-110, 1996.

33. Jensen, C. D., W. Haskell, and J. Whittman, ``Long-Term

Effects of Water-Soluble Dietary Fiber in the Management of

Hypercholesterolemia in Healthy Men and Women,'' American Journal of

Cardiology, 79:34-37, 1997.

34. Olson, B. H., S. M. Anderson, M. P. Becker, J. W. Anderson,

D. B. Hunninghake, D. J. A. Jenkins, J. C. LaRosa, J. M. Rippe, D.

C. K. Roberts, D. B. Stoy, C. D. Summerbell, A. S. Truswell. T. M.

S. Wolever, D. H. Morris, and V. L. Fulgoni III, ``Psyllium-Enriched

Cereals Lower Blood Total Cholesterol and LDL Cholesterol, but not

HDL Cholesterol, in Hypercholesterolemic Adults: Results of a Meta-

Analysis,'' Journal of Nutrition, 127:1973-1980, 1997.

35. Kellogg Co., ``Petition for Health Claim--Soluble Fiber from

Psyllium and Coronary Heart Disease,'' Item CP1, Docket 96P-0338,

Dockets Management Branch, June 12, 1996.

36. Anderson, J. W., N. Zettwoch, T. Feldman, J. Tietyen-Clark,

P. Oeltgen, and C. W. Bishop, ``Cholesterol-lowering Effects of

Psyllium Hydrophilic Mucilloid for Hypercholesterolemic Men,''

Archives of Internal Medicine, 148:292-296, 1988.

37. DHHS, National Heart, Lung, and Blood Institute, National

Cholesterol Education Program, ``Report of the Expert Panel on

Population Strategies for Blood Cholesterol Reduction (Population

Panel Report),'' Chapter II. Background and Introduction, NIH

Publication No. 93-3046, Bethesda, MD, 1993.

38. DHHS and USDA, ``Nutrition and Your Health: Dietary

Guidelines for Americans,'' 4th Ed., Home and Garden Bulletin No.

232, U.S. Government Printing Office, 1995.

39. LSRO, ``The Evaluation of the Safety of Using Psyllium Seed

Husk as a Food Ingredient,'' Bethesda, MD, December 1993.

40. Einspar, J. G., D. S. Alberts, S. M. Gapstur, R. M. Bostick,

S. S. Emmerson, and E. W. Gerner, ``Surrogate End-Point Biomarkers

as Measures of Colon Cancer Risk and Their Use in Cancer

Chemoprevention Trials,'' Cancer Epidemiology, Biomarkers and

Prevention, 6:37-48, 1997.

41. Whistler & Daniel, in Food Chemistry, 2nd Ed., Fennema, O.

R., ed. Marcel Dekker, Inc., New York, pp. 108-112, 1985.

42. Letter from V. L. Fulgoni, Kellogg's to C. J. Lewis, FDA,

December, 18, 1997.

43. Memorandum from A. S. Levy, FDA, to K. Falci, FDA, June 26,

1997.

List of Subjects in 21 CFR Part 101

Food labeling, Incorporation by reference, 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: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342,

343, 348, 371.

2. Section 101.17 is amended by adding paragraph (f) to read as

follows:

Sec. 101.17 Food labeling warning and notice statements.

* * * * *

(f) Foods containing psyllium husk. (1) Foods containing dry or

incompletely hydrated psyllium husk, also known as psyllium seed husk,

and bearing a health claim on the association between soluble fiber

from psyllium husk and reduced risk of coronary heart disease, shall

bear a label statement informing consumers that the appropriate use of

such foods requires consumption with adequate amounts of fluids,

alerting them of potential consequences of failing to follow usage

recommendations, and informing persons with swallowing difficulties to

avoid consumption of the product (e.g., ``NOTICE: This food should be

eaten with at least a full glass of liquid. Eating this product without

enough liquid may cause choking. Do not eat this product if you have

difficulty in swallowing.''). However, a product in conventional food

form may be exempt from this requirement if a viscous adhesive mass

[[Page 8119]]

is not formed when the food is exposed to fluids.

(2) The statement shall appear prominently and conspicuously on the

information panel or principal display panel of the package label and

any other labeling to render it likely to be read and understood by the

ordinary individual under customary conditions of purchase and use. The

statement shall be preceded by the word ``NOTICE'' in capital letters.

3. Section 101.81 is amended by revising the section heading, the

heading for paragraphs (a) and (b), and paragraphs (a)(3), (b)(2),

(c)(1), (c)(2)(i) introductory text, (c)(2)(i)(A), (c)(2)(i)(E),

(c)(2)(i)(F), (c)(2)(iii)(A), (d)(2), (d)(3), and (e); by adding

paragraphs (c)(2)(i)(G) and (c)(2)(ii)(B); and by removing paragraph

(d)(6) and redsignating paragraph (d)(7) as (d)(6) and paragraph (d)(8)

as (d)(7) to read as follows:

Sec. 101.81 Health claims: Soluble fiber from certain foods and risk

of coronary heart disease (CHD).

(a) Relationship between diets that are low in saturated fat and

cholesterol and that include soluble fiber from certain foods and the

risk of CHD. * * *

* * * * *

(3) Scientific evidence demonstrates that diets low in saturated

fat and cholesterol may reduce the risk of CHD. Other evidence

demonstrates that the addition of soluble fiber from certain foods to a

diet that is low in saturated fat and cholesterol may also help to

reduce the risk of CHD.

(b) Significance of the relationship between diets that are low in

saturated fat and cholesterol and that include soluble fiber from

certain foods and the risk of CHD. * * *

* * * * *

(2) Intakes of saturated fat exceed recommended levels in the diets

of many people in the United States. One of the major public health

recommendations relative to CHD risk is to consume less than 10 percent

of calories from saturated fat and an average of 30 percent or less of

total calories from all fat. Recommended daily cholesterol intakes are

300 milligrams (mg) or less per day. Scientific evidence demonstrates

that diets low in saturated fat and cholesterol are associated with

lower blood total- and LDL-cholesterol levels. Soluble fiber from

certain foods, when included in a low saturated fat and cholesterol

diet, also helps to lower blood total- and LDL-cholesterol levels.

(c) Requirements. (1) All requirements set forth in Sec. 101.14

shall be met. The label and labeling of foods containing psyllium husk

shall be consistent with the provisions of Sec. 101.17(f).

(2) Specific requirements. (i) Nature of the claim. A health claim

associating diets that are low in saturated fat and cholesterol and

that include soluble fiber from certain foods with reduced risk of

heart disease may be made on the label or labeling of a food described

in paragraph (c)(2)(iii) of this section, provided that:

(A) The claim states that diets that are low in saturated fat and

cholesterol and that include soluble fiber from certain foods ``may''

or ``might'' reduce the risk of heart disease.

* * * * *

(E) The claim does not attribute any degree of risk reduction for

CHD to diets that are low in saturated fat and cholesterol and that

include soluble fiber from the eligible food sources from paragraph

(c)(2)(ii) of this section; and

(F) The claim does not imply that consumption of diets that are low

in saturated fat and cholesterol and that include soluble fiber from

the eligible food sources from paragraph (c)(2)(ii) of this section is

the only recognized means of achieving a reduced risk of CHD.

(G) The claim specifies the daily dietary intake of the soluble

fiber source that is necessary to reduce the risk of coronary heart

disease and the contribution one serving of the product makes to the

specified daily dietary intake level. Daily dietary intake levels of

soluble fiber sources listed in paragraph (c)(2)(ii) of this section

that have been associated with reduced risk coronary heart disease are

:

(1) 3 g or more per day of B-glucan soluble fiber from whole oats.

(2) 7 g or more per day of soluble fiber from psyllium seed husk.

(ii) * * *

(B)(1) Psyllium husk from the dried seed coat (epidermis) of the

seed of Plantago (P.) ovata, known as blond psyllium or Indian

psyllium, P. indica, or P. psyllium. To qualify for this claim,

psyllium seed husk, also known as psyllium husk, shall have a purity of

no less than 95 percent, such that it contains 3 percent or less

protein, 4.5 percent or less of light extraneous matter, and 0.5

percent or less of heavy extraneous matter, but in no case may the

combined extraneous matter exceed 4.9 percent, as determined by U.S.

Pharmacopeia (USP) methods described in USP's ``The National

Formulary,'' USP 23, NF 18, p. 1341, (1995), which is incorporated by

reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies

may be obtained from the U.S. Pharmacopeial Convention, Inc., 12601

Twinbrook Pkwy., Rockville, MD 20852, or may be examined at the Center

for Food Safety and Applied Nutrition's Library, 200 C St. SW., rm.

3321, Washington, DC, or at the Office of the Federal Register, 800

North Capitol St. NW., suite 700, Washington, DC;

(2) FDA will determine the amount of soluble fiber that is provided

by psyllium husk by using a modification of the Association of Official

Analytical Chemists' (AOAC's) method for soluble dietary fiber (991.43)

described by Lee et al., ``Determination of Soluble and Insoluble

Dietary Fiber in Psyllium-containing Cereal Products,'' Journal of the

AOAC International, 78 (No. 3):724-729, 1995, which is incorporated by

reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies

may be obtained from the Association of Official Analytical Chemists

International, 481 North Frederick Ave., suite 500, Gaithersburg, MD

20877-2504, or may be examined at the Center for Food Safety and

Applied Nutrition's Library, 200 C St. SW., rm. 3321, Washington, DC,

or at the Office of the Federal Register, 800 North Capitol St. NW.,

suite 700, Washington, DC;

(iii) * * *

(A) The food product shall include:

(1) One or more of the whole oat foods from paragraph (c)(2)(ii)(A)

of this section, and the whole oat foods shall contain at least 0.75

gram (g) of soluble fiber per reference amount customarily consumed of

the food product; or

(2) Psyllium husk that complies with paragraph (c)(2)(ii)(B) of

this section, and the psyllium food shall contain at least 1.7 g of

soluble fiber per reference amount customarily consumed of the food

product;

* * * * *

(d) * * *

(2) The claim may state that the relationship between intake of

diets that are low in saturated fat and cholesterol and that include

soluble fiber from the eligible food sources from paragraph (c)(2)(ii)

of this section and reduced risk of heart disease is through the

intermediate link of ``blood cholesterol'' or ``blood total- and LDL-

cholesterol;''

(3) The claim may include information from paragraphs (a) and (b)

of this section, which summarize the relationship between diets that

are low in saturated fat and cholesterol and that include soluble fiber

from certain foods and coronary heart disease and the significance of

the relationship;

* * * * *

(e) Model health claim. The following model health claims may be

used in food labeling to describe the

[[Page 8120]]

relationship between diets that are low in saturated fat and

cholesterol and that include soluble fiber from certain foods and

reduced risk of heart disease:

(1) Soluble fiber from foods such as [name of soluble fiber source

from paragraph (c)(2)(ii) of this section and, if desired, the name of

food product], as part of a diet low in saturated fat and cholesterol,

may reduce the risk of heart disease. A serving of [ name of food]

supplies ________ grams of the [grams of soluble fiber specified in

paragraph (c)(2)(i)(G) of this section] soluble fiber from [name of the

soluble fiber source from paragraph (c)(2)(ii) of this section]

necessary per day to have this effect.

(2) Diets low in saturated fat and cholesterol that include

[________ grams of soluble fiber specified in paragraph (c)(2)(i)(G) of

this section] of soluble fiber per day from [name of soluble fiber

source from paragraph (c)(2)(ii) of this section and, if desired, the

name of the food product] may reduce the risk of heart disease. One

serving of [name of food] provides ________ grams of this soluble

fiber.

Dated: February 10, 1998

William B. Schultz,

Deputy Commissioner for Policy.

Note: The following table will not appear in the Code of Federal

Regulations.

Table 1.--Summary of Clinical Trials with Hypercholesterolemics: Psyllium and Coronary Heart Disease

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Supplements Diet Intake of

Study Duration Treatment Number of Subjects (Psyllium, Placebo) groups: Sat fat % E; Magnitude of PSY Magnitude of Placebo

Soluble Fiber g/d CHOL mg/d Effect\1\ Effect

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Anderson et Base: 8 wk Step 1; Tx: 26 PSY: 131 10.2 g/d bulk Sat fat: PSY- 8.3%; CHOL: -5 mg/dL CHOL: +5 (2.6%)

al. wk Step 1+supplement C: 28 laxative, cellulose C- 7.7% (2.1%)\1\ LDL-C: +6 (3.9%)

(Ref. 13) PSY: 7 g CHOL: PSY- 164 mg; C- LDL-C: -5 mg/dL HDL-C: no sig dif

SF 146 mg (2.9%)\1\ (grps)

Bell et al. Base: 12-wk Step 1; Tx: 8- PSY: 40 (20 men) 10.2 g/d bulk Sat fat: PSY- 8-10%; CHOL: -9 mg/dL CHOL: 0

(Ref. 14) wk Step 1+supplement Pla: 35 (18 men) laxative, cellulose C- 7.7-8.6% (4.2%) LDL-C: -0.2%

PSY: 7 g CHOL: PSY- 168 mg; C- LDL-C: -12 mg/dL HDL-C: no sig dif

SF 206 mg (7.7%) (grps)

Davidson et Base: 8-wk Step 1; Tx: 24- PSY 1 56 (31 men) 3.4 g, 6.8 g, 10.2 g/ SAT fat: PSY- 7- CHOL: - CHOL: +1.7%; LDL-C:

al. wk Step 1 + PSY or PSY 2 40 (24 men) d; incorporated 8.6%; C- 7-8.6% 3% (PSY 3) +3%

(Ref. 15) control food (3 servings/ PSY 3 43 (28 men) into foods: C CHOL: PSY 1- 151 mg; LDL-C: - HDL-C: No sig dif

d) C 59 foods: no PSY PSY 2- 181; PSY 3- 5% (PSY 3) (grps)

PSY 1: 169

2.3 g C- 145 mg

SF,

PSY 2:

4.6 g;

PSY 3: 7

g

Everson et Regular diet; 5-d Base; 2 20 men 15.3 g/d bulk SAT fat: PSY- 12%; C- CHOL: -14 mg/dL (- CHOL: -1.9%; LDL-C: -

al. 40-d periods; 11-d laxative, cellulose 13.2 % 5%) 2.7%

(Ref. 16) washout; crossover PSY: 10 CHOL: PSY- 296 mg; C- LDL-C: -15 mg/dL HDL-C: No sig dif

g SF 274 mg (8%) (grps)

Keane et al. Base: 12 wk Step 1; Tx: 26 PSY: 40 (18m, 24f) 10.2 g/d bulk SAT fat: PSY- 5%; C- CHOL: -8.7 mg/dL CHOL: +2 (1%)

(Ref. 18) wk Step 1+supplement C: 39 (7m, 32f) laxative, cellulose 5.3% (3%) LDL-C: 0

PSY: 7 g CHOL: PSY- 145.2 mg; LDL-C: -11.5 mg/dL HDL-C: no sig dif

SF C- 151.1 mg (5.9%)\1\ (grps)

Levin et al. Base: 8-wk Step 1; Tx: 16- PSY: 30 (26 men) 10.2 g/d bulk SAT fat: PSY- 6.7%; CHOL: -13 mg/dL CHOL: 0; LDL-C -

(Ref. 19) wk Step 1+supplement Pla: 28 (23 men) laxative, cellulose C- 6.3% (5.6%) 2.2%;

PSY: 7 g CHOL: PSY- 166 mg; C- LDL-C: -13 mg/dL HDL-C:

SF 135 mg (8.6%) +6%

(sig from PSY)

Stoy et al. 4-wk Step 1; Step 1 + 23 men Estimated 11.6 g/d SAT fat: PSY: 5.1% CHOL: -10 mg/dL (4%) HDL-C: No sig dif

(Ref. 23) (8x5x5 wks): Grp 1: PSY- PSY from cereal: (Grp 1) and 5.1% LDL-C: -11 mg/dL (grps)

Pla-PSY; Grp 2: Pla-PSY- 8 g SF; (Grp 2) (6%)

Pla Wheat cereal: Wheat: 4.5% (Grp 1)

3 g SF and 5.0% (Grp 2)

CHOL: PSY 141-165 mg

Wheat: 164 mg (Grp

1), 117-170 (Grp 2)

Stoy et al. 4-wk Step 1; Step 1 + 22 men Estimated 11.6 g/d SAT fat: PSY: 4.8 CHOL: -10 mg/dL (4%) HDL-C: No sig dif

(Ref. 24) (8x5x5 wks): Grp 1: PSY- PSY from cereal: (Grp 1) and 5.2% LDL-C: -11 mg/dL (grps)

Pla-PSY; Grp 2: Pla-PSY- 8 g SF; (Grp 2) (6%)

Pla Wheat cereal: Wheat: 4.7% (Grp 1)

3 g SF and 5.6% (Grp 2)

CHOL: PSY 155-163 mg

Wheat: 133 mg (Grp

1), 169-172 (Grp 2)

[[Page 8121]]

Wein- Base: 12 wk Step 1; Tx: 8 23 (16m, 7f) 10.2 g/d bulk SAT fat: PSY- 8.7%; CHOL: -9 mg/dL HDL-C: sig higher in

gand et al. wk Step 1+supplement, laxative, cellulose C- 9% (3.8%) PSY group

(Ref. 26) crossover PSY: 7 g CHOL: PSY- 162 mg; C- LDL-C: -11 mg/dL

SF 203-261 mg (6.2%)\1\

Jenkins et Base: 2 mo controlled Step Study 1: Study 1: Study 1: Study 1: Study 1:

al. 2 diets; Tx: 2- 1 mo Step 32 (15m, 17f) 11.4 g/d PSY in SAT fat: PSY- 4.6%; CHOL: -27 mg/dL\1\ CHOL: -13.6 (5%)\2\

(Ref. 30) 2 diets+ cereal, cereal C -4.6% (9.8%) LDL-C: -10 (5.5%)

crossover (7.8 g CHOL: PSY- 31 mg; C- LDL-C: -24 mg/dL\1\ HDL-C: -2 (3.3%)

SF), wheat bran 29 mg (12.6%)

MUFA: PSY- 6%; C- 6% HDL-C: -6.6 mg/dL

(11.3%)\1\

Study 2: Study 2: Study 2: Study 2: Study 2:

27 (12m, 15f) 12.4 g/d PSY in SAT fat: PSY- 6%; C- CHOL: -34 mg/dL\1\ CHOL: -29.5

cereal 6% (12.6%) (10.7%)\2\

(8.4 g CHOL: PSY- 22 mg; C- LDL-C: -27.9 mg/ LDL-C: -17 (9%)\2\

SF), wheat bran 22 mg dL\1\ (14.9%) HDL-C: -1.4 (2.6%)

MUFA: PSY- 12%; C- HDL-C: -4.3 mg/dL\1\

12% (8%)

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\1\ Significant differences between treatment and placebo groups unless otherwise indicated.

\2\ Significant change across the diet phase.

Abbreviations Used in Table 1

C Control

CHOL Blood total cholesterol

d Day

E Energy

g Gram

grp Group

HDL-C High density lipoprotein cholesterol

LDL-C Low density lipoprotein cholesterol

m/f Number of males, number of females

mg/dL Milligrams per deciliter

Pla Placebo

PSY Psyllium

Sat fat Saturated fat

SF Soluble fiber

Sig Dif Statistically significant difference

Step 1 30% kcals fat, Approximately

% Percent

[FR Doc. 98-4074 Filed 2-12-98; 4:18 pm]

BILLING CODE 4160-01-F