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

SUMMARY: The Food and Drug Administration (FDA) is proposing to

authorize the use, on food labels and in food labeling, of health

claims on the association between soluble fiber from psyllium husks and

reduced risk of coronary heart disease (CHD). FDA is proposing this

action in response to a petition filed by the Kellogg Co. (the

petitioner). The agency has tentatively concluded that, based on the

totality of publicly available scientific evidence, soluble fiber from

psyllium 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. Therefore, the agency is proposing 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 husks.

DATES: Written comments by August 5, 1997. The agency is proposing that

any final rule that may issue based upon this proposal become effective

upon its publication.

ADDRESSES: Submit written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Joyce J. Saltsman, Center for Food

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

200 C St. SW., Washington, DC 20204, 202-205-5916.

SUPPLEMENTARY INFORMATION:

I. Background

The Nutrition Labeling and Education Act of 1990

On November 8, 1990, the President signed into law the Nutrition

Labeling and Education Act of 1990 (the 1990 amendments) (Pub. L. 101-

535). 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.

In the Federal Register of January 6, 1993 (58 FR 2478), FDA

adopted a final rule that implemented the health claim provisions of

the act (hereinafter referred to as the 1993 health claims final rule).

In that final rule, 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 (Sec. 101.70(a)) and sets out the types

of information that any such petition must include (Sec. 101.70(d)).

These regulations became effective on May 8, 1993.

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 has authorized claims that relate to 8

of these 10 relationships.

In its review of the relationship between dietary fiber and

cardiovascular disease (CVD), the agency reviewed all relevant

scientific evidence on dietary fiber and its effects on serum

cholesterol. The agency started by examining the conclusions and

recommendations of the pertinent Federal Government reviews on this

topic area: the 1988 ``Surgeon General's Report on Nutrition and

Health'' (the Surgeon General's report) (Ref. 3) and the 1989 Food and

Nutrition Board, National Academy of Sciences' (FNB/NAS) ``Diet and

Health'' (Ref. 4). These two reports (Refs. 3 and 4) provided a

comprehensive review of the role of a broad range of nutrients,

including dietary fiber, in the development of a number of chronic

diseases, including heart disease. Because the FNB/NAS and Surgeon

General's report were done independently but concurrently, taken

together, they provide an authoritative picture of the state of

scientific opinion at the time that they were published in 1988 and

1989. Therefore, the agency began its review of the dietary fiber

evidence with studies that had been published since 1988. This evidence

included studies on all fibers and did not focus on any particular

individual fibers. While the agency denied the use in food labeling of

health claims relating total dietary fiber to reduced risk of CVD (58

FR 2552), it authorized a health claim relating diets low in saturated

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

that contain dietary fiber (particularly soluble fiber) to a reduced

risk of CHD, one of the most common, most frequently reported, and most

serious forms of CVD.

In denying the dietary fiber and CVD health claim, the agency

stated that it is difficult to determine the relationship between

dietary fiber and heart disease because dietary fiber is 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. Likewise,

wheat bran, oat bran, and rice bran (all heterogeneous mixtures of

fibers) are not similar in composition. The agency also noted that it

is very difficult to chemically analyze dietary fiber components, and

that, consequently, it is hard to correlate the role of specific fiber

components to health effects.

Based on its review of numerous authoritative documents, including

Federal Government reports and recent research on dietary fiber and

CHD, and on its consideration of comments received in response to the

proposed rule entitled ``Health Claims; Dietary Fiber and

Cardiovascular Disease'' (56 FR 60582, November 27, 1991) (hereinafter

referred to as the 1991 dietary fiber and CVD proposal), FDA concluded

that the publicly available scientific evidence supported an

association between diets low in saturated fat and cholesterol and high

in fruits, vegetables, and grain products (i.e., foods that are low in

saturated fat and cholesterol and that are good sources of dietary

fiber) and reduced risk of heart disease (58 FR 2552 at 2572). The

agency further stated that, although the specific roles of the numerous

potentially protective substances in such plant foods were not yet

understood, populations with diets rich in these foods experience many

health advantages, including lower rates of heart disease. The agency

noted, however, that there was no scientific agreement as to whether

the observed protective effects against heart disease were the result

of the combination of nutrient components of the foods, including

soluble fiber; of the other components of soluble fiber-rich diets (for

example, potassium and magnesium); of the displacement of saturated fat

and cholesterol from the diet; or of nonnutritive substances in these

foods.

For all these reasons, the agency stated that the fact that these

foods contain dietary fiber, particularly soluble fiber, could serve as

a useful marker for identifying those fruits, vegetables, and grain

products that,

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when added to diets low in saturated fat and cholesterol, may help in

reducing blood low density lipoprotein (LDL)-cholesterol levels (58 FR

2552 at 2572). Thus, the agency 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, fruit, and grain

products that contain soluble fiber and a reduced risk of heart

disease.

In the 1993 dietary fiber and CVD final rule, in response to a

comment regarding the apparent hypocholesterolemic properties of

specific food fibers, e.g., oats, FDA agreed that the effectiveness of

naturally occurring fibers in foods may be documented for specific food

products (e.g., oat brans meeting specified parameters) (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 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 the Federal Register of January 23, 1997, FDA published a final

rule on the relationship between soluble fiber from whole oats and

reduced risk of coronary heart disease (the soluble fiber from whole

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

at 62 FR 15343, March 31, 1997). In that document, the agency concluded

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

fiber, is the primary component responsible for the hypocholesterolemic

properties associated with consumption of whole oat products as part of

a diet that is low in saturated fat and cholesterol (62 FR 3584 at

3585). The agency based its conclusions on the totality of publicly

available evidence, taking into account evidence showing that

consumption of -glucan soluble fiber from whole oats has the

effect of lowering blood total- and LDL-cholesterol in both humans and

animals (62 FR 3584 at 3586).

The agency also acknowledged the likelihood that consumption of

-glucan soluble fiber from sources other than whole oats, as

well as that from certain other non -glucan soluble fibers,

will affect, as part of an appropriate diet, blood lipid levels (62 FR

3584 at 3587). Although the agency considered structuring the final

rule as one on ``soluble fiber from certain foods'' and the risk of CHD

to allow flexibility in expanding the claim to other sources of soluble

fiber, it stated that it was premature to do so inasmuch as the agency

had not reviewed the totality of evidence on other, non-whole oat

sources of soluble fiber. However, FDA structured Sec. 101.81 in a way

that, while the regulation covered -glucan soluble fiber from

whole oats, would allow it to be amended as evidence becomes available

to support the use of the claim for other sources of soluble fiber.

The present rulemaking is in response to a manufacturer's health

claim petition on the relationship between soluble fiber from psyllium

and the risk of heart disease.

II. Petition for Health Claim on Psyllium and Reduced Risk of CHD

A. Background

On June 12, 1996, the Kellogg Co. submitted a petition to FDA

requesting that the agency authorize a health claim on the relationship

between consumption of soluble fiber from psyllium (specifically from

psyllium husks) and the risk of CHD (Ref. 1). On September 18, 1996,

the agency sent the petitioner a letter stating that it had completed

its initial review of the petition, and that the petition would be

filed in accordance with section 403(r)(4) of the act (21 U.S.C.

343(r)(4)) (Ref. 2). In this document, the agency will consider whether

a health claim on this nutrient-disease relationship is justified under

the standard in section 403(r)(3)(B)(i) of the act and in

Sec. 101.14(c) of FDA's regulations. The following is a review of the

health claim petition.

B. Preliminary Requirements

1. The Substance Is Associated With a Disease for Which the U.S.

Population Is at Risk

The regulations authorizing claims on dietary saturated fat and

cholesterol and risk of CHD (Sec. 101.75 (21 CFR 101.75)); fruits,

vegetables, and grain products that contain soluble fiber and risk of

CHD (Sec. 101.77); and soluble fiber from whole oats and risk of CHD

(Sec. 101.81) establish that CHD is a disease for which the U.S.

population is at risk. In adopting those regulations, FDA stated that

CHD remains a major public health problem, the number one cause of

death in the United States. Despite the decline in deaths from CHD over

the past 30 years, this disease is still exacting a tremendous toll in

morbidity and mortality (Refs. 3 through 5). There are more than

500,000 deaths each year for which CHD is an underlying cause, and

another 250,000 deaths for which CHD is a contributing cause. About 20

percent of American adults ages 20 to 74 years have blood total

cholesterol levels in the ``high'' category (total cholesterol greater

than or equal to () 240 milligrams (mg) per (/) deciliter

(dL) or LDL-cholesterol 160 mg/dL) (Ref. 6). Another 31

percent have ``borderline'' cholesterol levels (total cholesterol

between 200 to 239 mg/dL). Therefore, based on these facts as presented

in Secs. 101.75, 101.77, and 101.81, FDA tentatively concludes that the

requirement in Sec. 101.14(b)(1) has been met.

2. The Substance is a Food

Psyllium is a harvestable grain from plants of the Plantago genus

(Ref. 1, p. 5-6). Different types of psyllium are available, depending

on the growing region. It is primarily cultivated in France, Spain, and

India, with some small quantities grown in the American Southwest.

Psyllium husk (also known as psyllium seed husk), which comes from the

dried coat of the psyllium seed, is used as a food or food component in

a number of foods in the United States (Ref. 1, p. 9-11) and is the

source of psyllium soluble fiber that is the subject of the petition.

Psyllium husk is a concentrated source of soluble fiber and contributes

certain technical effects (e.g., as a stabilizer) that are retained

when it is consumed at levels necessary to justify the petitioned

claim.

Therefore, FDA tentatively concludes that the substance satisfies

the preliminary requirements of Sec. 101.14(b)(3)(i).

3. The Substance Is Safe and Lawful

The petitioner has also submitted a petition requesting that FDA

affirm that the use of psyllium husk in grain-based foods is generally

recognized as safe (GRAS) (55 FR 4481, February 8, 1990). The agency

notes that this GRAS affirmation petition (GRASP 0G0357) is still under

review, and that authorization of a health claim should not be

interpreted as affirmation that the petitioned uses of psyllium are

GRAS. Such a determination can be made only after the agency has

completed its review of the GRAS petition. A preliminary review of the

GRAS affirmation petition, however, reveals that it contains

significant evidence supporting the safety of the use of this substance

at the levels necessary to justify a health claim.

In its GRAS affirmation petition, the petitioner relied heavily on

the conclusions about the safety of psyllium by the Life Sciences

Research Office (LSRO) of the Federation of American Societies for

Experimental Biology (FASEB) (Ref. 1, pp. 12-17). In its 1993 report

entitled ``The Evaluation of the Safety of Using Psyllium Husk as a

Food Ingredient,'' LSRO reviewed and

[[Page 28236]]

evaluated published data, unpublished studies that were in press at

that time, and other information and data. Based on this review, LSRO

concluded that:

There is no evidence in the available information on psyllium

that demonstrates or suggests reasonable grounds to suspect a hazard

to the public when it is used in a number of food categories and at

levels of addition that would result in total consumption of as much

as 25 g/day of psyllium. However, it is not possible to determine

without additional data whether a significant increase in

consumption above 20 to 25 g/day would constitute a dietary hazard.

(Ref. 31, p. 57.) The agency is not prepared to disagree with LSRO's

conclusions on the safety of psyllium husk.

The agency points out, however, that some concerns about the safety

of psyllium do exist. For example, available information suggests that

long-term exposure to high levels of psyllium husk may enhance

epithelial cell proliferation in the gastrointestinal tract. Rats

consuming an elemental diet containing 30 percent fiber supplement, of

which 10 percent was Ispaghula (psyllium), had increased cell

proliferation in the stomach, distal small intestine, and colon when

compared to rats consuming an elemental diet with no fiber supplement

(Ref. 36). There is no agreement in the scientific community, however,

whether such an increase in cell proliferation is related to an adverse

health effect (Ref. 37). FDA requests comments on whether enhanced

proliferation of gastrointestinal tract epithelial cells as a result of

long-term exposure to psyllium husk is of concern, and whether it would

provide a basis for not authorizing a claim.

The agency is also aware that psyllium husk can cause allergic

reactions in some people, such as health care professionals, who

regularly dispense psyllium containing products in the course of their

work. Information provided by the petitioner (Ref. 32) shows that there

are at least 13 protein fractions present in psyllium husk

preparations. Some of these protein fractions cross react with sera

obtained from individuals who experienced allergic reactions to

psyllium-containing foods. The information also shows that refinement

of psyllium husk preparations, i.e., increasing the purity of psyllium

husk, by mechanical sieving can reduce the level of antigenic protein

fractions (Ref. 32).

Because of concerns regarding the allergenic potential of products

derived from psyllium seed, FDA is proposing specifications for the

purity of the psyllium husk that is the subject of this health claim

proposal to reduce the potential for allergic reactions to foods

containing added psyllium. These specifications are based on

information provided in the petition (Ref. 32) and on the

specifications used by the petitioner (Ref. 1). FDA requests comments

on the adequacy of these proposed specifications to reduce the

allergenic potential of psyllium husk consumed as a component of food.

Are other steps, such as requiring that a psyllium-containing product

that bears a health claim declare on its prinicipal display panel that

psyllium is present in the food, necessary?

Additionally, the agency is aware of the potential for

gastrointestinal obstruction to occur following consumption of psyllium

husk in the absence of sufficient liquid to ensure thorough hydration.

However, the 1993 report by LSRO noted that reports of gastrointestinal

obstruction have been associated almost exclusively with consumption of

bulk laxatives without proper hydration (Ref. 31). Moreover, LSRO

stated that there have been no such reports associated with the

consumption of psyllium-containing cereals consumed with milk. It also

noted that there are no data regarding possible alimentary tract

obstruction that could be associated with consumption of psyllium-

containing products such as poptarts, waffles, breads, and other foods

that may be consumed without a liquid (Ref. 31). LSRO stated that the

moderate amount of psyllium in these products would not be expected to

cause gastrointestinal obstruction, and that any such possibility would

be reduced by a suitable suggestion that these products be consumed

with fluids (Ref. 31). The agency is asking for comments on whether

psyllium-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-containing food.

Based on the totality of the evidence, the agency is not prepared,

at this time, to take issue with the petitioner's view that the use of

psyllium husk is safe and lawful. Although FDA tentatively concludes

that the petitioner has provided evidence that satisfies the

requirement in Sec. 101.14(b)(3)(ii) that use of psyllium husk at the

levels necessary to justify a claim is safe and lawful, the agency

requests comment on this tentative conclusion. The agency recognizes

that, should this proposed health claim be authorized, there may be an

increase in the consumption of psyllium. Therefore, the agency also

requests comments on actions, if any, that may be necessary to ensure

that longterm consumption of psyllium will be at safe levels, such as

establishing a maximum psyllium content that foods may contain to bear

the health claim or limiting the kinds of foods that can contain

psyllium and bear a claim.

III. Review of Scientific Evidence

A. Basis for Evaluating the Relationship Between Soluble Fiber from

Psyllium and CHD

In the 1991 dietary fiber and CVD proposal, the agency set forth

the basis for the relationship between dietary fiber and CVD (56 FR

60582 at 60583). In that document, the agency stated that there are

many risk factors that contribute to the development of CVD, and

specifically CHD, one of the most serious forms of CVD and the leading

cause of disability. The agency also stated that there is general

agreement that elevated blood cholesterol levels are one of the major

``modifiable'' risk factors in the development of CVD and, more

specifically, CHD.

The Federal Government and others who have reviewed the matter have

concluded that there is substantial epidemiologic evidence that high

blood levels of total cholesterol and LDL-cholesterol are a cause of

atherosclerosis (inadequate circulation of blood to the heart due to

narrowing of the arteries) and represent major contributors to CHD (56

FR 60582 at 60583, Refs. 3 through 5). Factors that decrease total

cholesterol and LDL-cholesterol will also tend to decrease the risk of

CHD. High intakes of saturated fat and, to a lesser degree, of dietary

cholesterol are associated with elevated blood total and LDL-

cholesterol levels (56 FR 60727 at 60728, November 27, 1991). Thus, it

is generally accepted that blood total cholesterol and LDL-cholesterol

levels can influence the risk of developing CHD, and, therefore, that

dietary factors affecting blood total cholesterol levels affect the

risk of CHD (Refs. 3 through 5).

When considering the effect that the diet or components of the diet

have on blood (or serum) lipids, it is also important to consider the

effect that these factors may have on blood levels of high density

lipoprotein-cholesterol (HDL-cholesterol). HDL-cholesterol is involved

in the regulation of cholesterol transport out of cells and to the

liver, from which it is ultimately excreted (Refs. 3 and 33).

Therefore, HDL-cholesterol has a protective effect in the body by

helping to reduce the risk of CHD.

[[Page 28237]]

For these reasons, FDA limited its review of the relationship

between soluble fiber from the psyllium husk, hereinafter referred to

as ``psyllium,'' and CHD to effects of dietary intake of this substance

on blood lipid levels and on the risk of developing CHD. The agency

based its evaluation of the relationship between consumption of this

substance and CHD on changes in blood total cholesterol, LDL-

cholesterol, and HDL-cholesterol, resulting from dietary intervention

with soluble fiber from psyllium and with psyllium-containing products.

This focus is consistent with that used by the agency in response to

the 1990 amendments in deciding on the dietary saturated fat and

cholesterol and CHD health claim, Sec. 101.75 (56 FR 60727 and 58 FR

2739); the fruits, vegetables, and grain products and CHD claim,

Sec. 101.77 (56 FR 60582 and 58 FR 2552); and the soluble fiber from

whole oats and CHD claim, Sec. 101.81 (61 FR 296 and 62 FR 3584).

B. Review of Scientific Evidence

1. Evidence Considered in Reaching the Decision

The petitioner submitted scientific studies evaluating the

relationship between soluble fiber from psyllium, consumed as a food

and as an ingredient in foods, and serum lipid levels (Ref. 1). These

studies were conducted between 1965 and 1996. The petition included

tables that summarized the outcome of those studies and a summary of

the evidence. Consistent with the approach taken in the dietary fiber/

CVD proposed rules, the agency began its review by considering those

psyllium studies that were published since 1988 (date of publication of

the Surgeon General's report). In addition, in its review of the

petition, the agency considered the conclusions of two LSRO reports

(Refs. 7 and 8) relative to studies involving psyllium.

2. Criteria for Selection of Human Studies

The criteria that the agency used to select pertinent studies were

that the studies: (1) Present data and adequate descriptions of the

study design and methods; (2) be available in English; (3) include

estimates of, or enough information to estimate, soluble dietary fiber

intakes; (4) include direct measurement of blood total cholesterol and

other blood lipids related to CHD; and (5) be conducted in persons who

represent the general U.S. population (adults with blood total

cholesterol levels less than (-glucan

soluble fiber from whole oats, may affect serum lipid levels and thus

help to reduce the risk of CHD (62 FR 3584 at 3587). The agency further

stated that if a manufacturer can document, through appropriate human

and laboratory studies, that a soluble fiber has an effect on blood

total- and LDL-cholesterol levels, and thereby can be useful in

reducing the risk of CHD, the manufacturer may petition to amend

Sec. 101.81 to include that source of soluble fiber among the food

sources about which claims are authorized (62 FR 3584 at 3587 and

3588). The agency explained that it was necessary to evaluate each

source of soluble fiber individually because soluble fiber is a family

of very heterogeneous substances that vary greatly in their effect on

the risk of CHD.

The agency tentatively concludes that the soluble fiber in

psyllium, like -glucan soluble fiber from whole oats, when

consumed as part of a diet low in saturated fat and cholesterol, may

help to reduce the risk of heart disease, and that a health claim

describing this relationship is warranted. To this end, the agency is

proposing to amend Sec. 101.81, as discussed below, to include soluble

fiber from psyllium and to broaden the subject of the claim to

``soluble fiber from certain foods'' and risk of CHD.

As discussed in the preamble to the soluble fiber from whole oats

final rule, an umbrella regulation for ``soluble fiber from certain

foods'' and CHD will provide flexibility for the inclusion of other

food sources of soluble fiber when adequate data are provided to

demonstrate that consumption of those foods may help to reduce the risk

of heart disease (62 FR 3584 at 3588). Moreover, such an umbrella

regulation has the advantage of minimizing consumer confusion in that

the claim could not be used on the label of all foods that contain

soluble fiber. Rather, the claim will be limited to those soluble fiber

sources whose consumption has been demonstrated to have a relationship

to the risk of CHD.

VI. Description of Modifications to Sec. 101.81

A. Eligible Sources of Soluble Fiber

Section 101.81(c)(2)(ii) (``Nature of the substance. Eligible

sources of soluble fiber'') lists the types and sources of soluble

fiber that have been demonstrated to the satisfaction of FDA to have a

relationship to the risk of CHD. In Sec. 101.81(c)(2)(ii)(A), FDA lists

-glucan soluble fiber from the whole oat sources, along with

the method of analysis for -glucan soluble fiber by the

Association of Official Analytical Chemists. Section

101.81(c)(2)(ii)(A)(1) through (c)(2)(ii)(A)(3) identify the whole oat

sources that are eligible to bear the claim. FDA reserved

Sec. 101.81(c)(2)(ii)(B) for future use.

In this document, FDA is proposing 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. As discussed in

section II.B.3 of this document, the agency is aware that psyllium has

been associated with allergic reactions in some people, especially in

health care professionals who dispense psyllium containing products in

the course of their work. The petitioner stated that using psyllium

with a purity of 95 percent in cereal significantly reduced the

potential for allergenic responses following consumption of psyllium-

containing food (Ref. 1, pp. 85-86). Information provided by the

petitioner showed that psyllium husk that has a purity of 95 percent

has a maximum protein content of 3 percent and total extraneous matter

not to exceed 4.9 percent (i.e., 4.5 percent or less of light

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

as determined by USP methods (Ref. 34)).

In this document, the agency is proposing to adopt these

specifications for psyllium husk that may be the subject of a claim.

Therefore, proposed Sec. 101.81(c)(2)(ii)(B)(1) states that ``to

qualify for this claim, psyllium husk shall have a purity of no less

than 95 percent, such that it has a 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'' that are incorporated by reference (Ref. 1, pp. 5-6, and Ref.

34). The agency requests comments on whether the requirements proposed

in Sec. 101.81(c)(2)(ii)(B)(1) are sufficient to reduce the potential

for allergenic responses in individuals sensitive to psyllium.

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

the dried seed coat (epidermis) of the seed of Plantago (P) ovata,

known as blond psyllium or Indian psyllium; P. indica; or P. psyllium.

This information is consistent with that provided by the petitioner

(Ref. 1, pp. 5 and 6) and the description of psyllium husk given in the

U.S. Pharmacopeia's (USP) ``The National Formulary'' (Ref. 34).

In proposed Sec. 101.81(c)(2)(ii)(B)(2), FDA identifies the

analytical method that it intends to use to determine the amount of

soluble fiber that is provided by psyllium. Because psyllium-containing

food products are highly viscous in aqueous solutions and may not be

easily filtered, a method for analyzing for soluble and insoluble

dietary fiber from psyllium was developed by Lee et al. (Ref. 29). The

assay, a modification of method No. 991.31 from ``Official Methods of

Analysis of the Association of Official Analytical Chemists'' (AOAC),

appeared in the Journal of the AOAC International, volume 78, page 724,

1995, and FDA is proposing to incorporate it by reference in accordance

with 5 U.S.C. 552(a) and 1 CFR part 51 in this document.

B. Nature of the Food Eligible to Bear the Claim

Section 101.81(c)(2)(iii)(A) (as modified at 62 FR 15342) states

that ``the food product shall include one or more of the whole oat

foods from paragraph (c)(2)(ii) 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'' (RACC). FDA arrived

at this amount of soluble fiber by dividing an intake of 3 g/d soluble

fiber from whole oats by 4 eating occasions per day (62 FR 3584 at

3592). The daily intake of 3 g soluble fiber was based on an analysis

of data from a dose-response study that showed that an intake of 3 g/d

-glucan soluble fiber from whole oats was associated with a

significant reduction (5 percent) in blood total- and LDL-cholesterol

levels, and the results of a meta-analysis and other oat studies (61 FR

296 at 308). Based on four eating occasions per day, each serving of

the eligible whole oat product would have to provide a minimum of 0.75

g per RACC as part of the requirements to qualify to bear the CHD

claim.

The petitioner for the psyllium claim stated that ``the

hypocholesterolemic dose-responsiveness of soluble fiber from psyllium

(i.e., psyllium husk) has not been extensively studied, but there is

evidence to suggest that the greater

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the dose, the more pronounced the cholesterol-lowering effects will

be'' (Ref. 1, p. 100). The petitioner noted LSRO's (Ref. 7)

recommendations for soluble fiber intake for the general U.S.

population. LSRO stated that soluble fiber should account for 25 to 30

percent of the total dietary fiber intake and recommended a daily

intake of total dietary fiber intake of between 20 to 35 g/d (Ref. 7).

Based on these values, an optimal intake of soluble fiber intake would

range from 5 g/d to about 10.5 g/d.

The petitioner also reviewed the results of studies that evaluated

the effects of different intake levels of psyllium and considered the

conclusions of reviews of the literature on psyllium (Ref. 1, pp. 100

through 102). It noted that some overviews of the literature on

psyllium and serum cholesterol levels have suggested intake ranges of

10 to 30 g/d of psyllium (Ref. 1, p. 100). The petitioner also noted

that the results of the dose-response study by Davidson et al. (Ref.

15) showed that the group consuming 10.2 g/d of psyllium had

differences of approximately 4.6 percent for LDL-cholesterol and 3.3

percent for total cholesterol when compared to controls (Ref. 1, p.

101). Based on all of the evidence, the petitioner asserted that an

intake of about 7 g/d soluble fiber from 10.2 g/d psyllium may help to

reduce the risk of CHD (Ref. 1, p. 102).

The petitioner suggested that, based on a daily intake level of

10.2 g of psyllium, which provides about 7 g soluble fiber, the level

in a food to qualify to bear the CHD claim should be 2.5 g of psyllium

per RACC (10.2 g/d divided by 4 eating occasions per day), which

provides 1.7 g soluble fiber (7 g/d of soluble fiber divided by 4) per

RACC. The petitioner noted that the agency has usually assumed that

food consumption patterns generally reflect three meals and a snack (58

FR 2302 at 2379, January 3, 1993).

After review of data from studies submitted with the petition, the

agency notes that, with the exception of the dose-response study by

Davidson et al. (Ref. 15), psyllium was consumed in these studies at

levels of 10 or more g/d (soluble fiber was approximately 7 g/10 g of

psyllium) (see Table 1 and Ref. 35). In those placebo-controlled

studies that tested an intake of psyllium of 10.2 g, the effect on

serum blood lipids was consistent, i.e., blood total and LDL-

cholesterol levels were significantly lowered, and HDL-cholesterol

levels were not affected (Refs. 10, 11, 13 through 15, 18, 19, 22, and

26).

As noted earlier, Davidson et al. (Ref. 15) evaluated the effect of

psyllium at levels of 3.4 g (Group 1), 6.8 g (Group 2), and 10.2 g

(Group 3) per day from foods consumed as part of a Step 1 diet. The

results of the study showed significant lowering of serum lipids in

subjects consuming 10.2 g/d psyllium in food. The authors stated,

however, that the subjects in the first two groups may not have

complied with study protocol, thus confounding the results for them.

Because of the potential for confounding in this study, the agency

finds that the results of the Davidson study do not provide the

information needed to determine a dose-response between the level of

psyllium intake, and therefore the level of soluble fiber from

psyllium, and the degree of change in blood lipid levels.

In this document, the agency is proposing to amend Sec. 101.81 to

add soluble fiber from psyllium, but it does not have the data that

were available for -glucan soluble fiber from whole oats on

which to establish a dose-response based qualifying level for the

amount of soluble fiber from psyllium necessary for a food to be

eligible to bear the claim. As discussed above, relative to whole oat

soluble fiber qualifying levels, analysis of data from a dose-response

study showed that an intake of 3 g/d whole oat soluble fiber was

associated with a 5 percent reduction in blood lipids (61 FR 296 at

308). In the whole oat proposal, the agency explained that a

significant reduction in serum lipids of 5 percent is associated with

the level that was achieved as a result of a dietary fat and

cholesterol-focused intervention in the Multiple Risk Factor

Intervention Trial and Lipid Research Council clinical trials (61 FR

296 at 308). The agency does not have similar data from which to

determine the amount of soluble fiber from psyllium that is associated

with a 5 percent reduction in serum lipids.

In the absence of such data, the agency is tentatively proposing to

base the qualifying level of soluble fiber from psyllium on a total

daily intake of 10.2 g (about 7 g of soluble fiber), as suggested by

the petitioner. This level of intake was shown in the clinical studies

to be consistently associated with significant reductions in serum

lipids.

Therefore, FDA is proposing that the qualifying level of soluble

fiber for foods to bear this claim be 1.7 g soluble fiber from psyllium

per RACC (7 g divided by 4 eating occasions per day). The agency does

not consider it necessary to propose a qualifying amount of psyllium as

suggested in the petition (2.5 g) because the qualifying level of

soluble fiber will determine the amount of psyllium that is required.

Based on estimates from figures provided in the petition and in the

studies, psyllium is about 68 percent or more soluble fiber. Therefore,

1.7 g/RACC of soluble fiber from psyllium would relate to about 2.5 g/

RACC of psyllium husk. The agency is asking for comments on whether

this approach for establishing a qualifying soluble fiber level for

psyllium-containing products is appropriate or for data to support

another qualifying level for psyllium.

Health claims help consumers to identify those products that will

help them achieve a healthy diet (see, e.g., section 403(r)(3)(B)(iii)

of the act). Expanding Sec. 101.81 to include psyllium-containing foods

will give consumers an opportunity to select from a wider variety of

foods containing those soluble fibers that have been shown to help

reduce the risk of CHD. The availability of a variety of foods, in

turn, should help consumers increase their daily intake of soluble

fiber.

To reflect the agency's tentative decision to propose a qualifying

level of soluble fiber from psyllium that is different from that

required for whole oats, the agency is proposing to amend

Sec. 101.81(c)(2)(iii)(A) (as modified at 62 FR 15342) to set out the

qualifying level of soluble fiber from whole oat and psyllium foods.

Therefore, in this document, proposed Sec. 101.81(c)(2)(iii)(A) is

modified to state ``[T]he food product shall include:'' followed by

paragraphs (1) and (2). Paragraph (c)(2)(iii)(A)(1) is modified to

state ``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.'' FDA is proposing to state in

Sec. 101.81(c)(2)(iii)(A)(2): ``psyllium 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.''

The agency recognizes that foods could be produced with a blend of

the eligible soluble fibers listed in paragraph (c)(2)(ii) and would be

willing to consider whether such foods should be eligible to bear the

health claim. An example of a product that contains a blend of the

eligible soluble fibers might be one that contains 75 percent of the

qualifying level of -glucan soluble fiber from whole oats and

25 percent of the qualifying level of soluble fiber from psyllium.

However, the agency does not have the data on which to evaluate the

relationship between consumption of foods containing both psyllium and

whole oats and risk of heart disease. Although

[[Page 28241]]

both soluble fiber sources affect the same CHD risk factor (i.e., blood

lipid levels), the agency cannot assume that foods containing a blend

of these grains would have the same ability to affect blood total and

LDL-cholesterol levels that a product containing either whole oats or

psyllium apparently has. Therefore, if a manufacturer can demonstrate

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)(A) and (c)(2)(ii)(B) has an effect on the risk of

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

further. In addition, because the qualifying level that FDA is

proposing for soluble fiber from psyllium differs from that which it

adopted for -glucan soluble fiber from whole oats, the issue

of an appropriate qualifying level for a blended product should be

addressed in any petition.

In the preamble to the final rule in which it adopted Sec. 101.81,

the agency explained that the approach it used to derive the qualifying

level of 0.75 g per RACC for whole oat products is somewhat different

from the one that it used in authorizing other health claims (62 FR

3584 at 3592). The agency explained that the guiding principle for

other health claims was to use the established definition for ``good

source'' or ``high in,'' which characterize the amount of a nutrient

based on a percentage of the Daily Reference Value (DRV) for the

nutrient, in a serving of food as the qualifying level. 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. However, there is no DRV for soluble

fiber. While the agency concluded that the approach it took to

establish the qualifying level in Sec. 101.81 was appropriate, it

stated that it intends to propose to establish a DRV for soluble fiber,

and, once that rulemaking is completed, assuming it results in a DRV,

it would revisit the requirements in Sec. 101.81 and propose any

changes in its provisions that are necessary. For the purposes of any

final rule that results from this rulemaking, the agency will also

revisit the requirements of Sec. 101.81(c)(2)(iii) if a DRV is

established for soluble fiber.

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

In light of the agency's tentative decision to broaden Sec. 101.81

to include soluble fiber from psyllium, the agency is proposing to

modify the section heading of Sec. 101.81 from ``Soluble fiber from

whole oats and risk of coronary heart disease'' to ``Health claims:

soluble fiber from certain foods and risk of coronary heart disease.''

The statement ``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., -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.

The statement ``soluble fiber from whole oats'' also appears in

several paragraphs of Sec. 101.81. The agency is proposing to revise

this statement where it appears to state ``soluble fiber from certain

foods.'' The paragraphs of Sec. 101.81 that will be affected by this

change, if it is adopted, include: (a), (a)(3), (b), (b)(2), (c)(2)(i),

(c)(2)(i)(A), (d)(3), and (e).

The agency is proposing to revise the statement ``soluble fiber

from whole oats'' in three paragraphs of Sec. 101.81, paragraphs

(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.''

The agency tentatively finds that the statement ``soluble fiber from

the eligible food sources * * *'' more accurately identifies the

particular sources of soluble fibers that may be the subject of the

claim. For example, Sec. 101.81(c)(2)(i)(E) now specifies that the

claim must not attribute any degree of risk reduction for coronary

heart disease to diets low in saturated fat and cholesterol that

include soluble fiber from whole oats. The eligible food sources in

this proposed rule include whole oats and psyllium, so FDA is proposing

to revise Sec. 101.81(c)(2)(i)(E) to reflect the broader coverage of

the claim.

The agency notes, however, that it is not proposing changes to the

model claims in Sec. 101.81(e) (modified at 62 FR 15342). In both

example claims, the name of the soluble fiber source from

Sec. 101.81(c)(2)(ii) (Eligible source of soluble fiber) is provided,

and, if desired, the name of the food product may be provided. For

example, Sec. 101.81(e)(1) states ``Soluble fiber from foods such as

[name of soluble fiber source from section (c)(2)(ii) of this section

and, if desired, the name of the food product], as part of a diet low

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

disease.'' Therefore, a claim for a psyllium-containing food may state

``Soluble fiber from foods such as psyllium, as part of a diet low in

saturated fat and cholesterol, may reduce the risk of heart disease,''

and thus no change in Sec. 101.81(e)(1) or (e)(2) is necessary to

reflect the addition of psyllium to the list of substances eligible to

bear the claim.

The agency is proposing to make some minor editorial changes in

Sec. 101.81, which have no substantive effect on this regulation.

VII. Environmental Impact

The agency has determined under 21 CFR 25.24(a)(11) that this

action is of a type that does not individually or cumulatively have a

significant effect on the human environment. Therefore, neither an

environmental assessment nor an environmental impact statement is

required. This finding is based on information submitted by the

petitioner in an environmental assessment prepared using the format

described in 21 CFR 25.31a(b)(5).

VIII. Analysis of Impacts

FDA has examined the impacts of the proposed rule under Executive

Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612).

Executive Order 12866 directs agencies to assess all costs and benefits

of available regulatory alternatives and, when regulation is necessary,

to select regulatory approaches that maximize net benefits (including

potential economic, environmental, public health and safety, and other

advantages; distributive impacts; and equity). Executive Order 12866

classifies a rule as significant if it meets any one of a number of

specified conditions, including having an annual effect on the economy

of $100 million or adversely affecting in a material way a sector of

the economy, competition, or jobs, or if it raises novel legal or

policy issues. 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. FDA finds that this

proposed rule is not a significant rule as defined by Executive Order

12866 and finds under the Regulatory Flexibility Act that the proposed

rule will not have a significant impact on a substantial number of

small entities.

The establishment of this health claim results in benefits and in

costs only to the extent that food manufacturers elect to take

advantage of the opportunity to use the claim. This rule will not

require that any labels be redesigned or that any product be

reformulated.

Some manufacturers are currently using FDA's approved health claim

regarding the benefits of fruits, vegetables, and grain products. This

proposed health claim will allow them to specifically highlight the

role of

[[Page 28242]]

soluble fiber from psyllium. The benefit of establishing this health

claim is to provide for new information in the market regarding the

relationship of soluble fiber from psyllium and CHD.

Costs will be incurred by small entities 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 Commissioner of Food

and Drugs certifies that the proposed rule will not have a significant

economic impact on a substantial number of small entities. Therefore,

under the Regulatory Flexibility Act, no further analysis is required.

IX. Paperwork Reduction Act

FDA tentatively concludes that this proposed rule contains no

reporting, recordkeeping, labeling, or other third party disclosure

requirement. Thus, there is no ``information collection'' necessitating

clearance by the Office of Management and Budget. However, to ensure

the accuracy of this tentative conclusion, FDA is seeking comment on

whether this proposed rule to permit health claims on the association

between soluble fiber from psyllium and reduced risk of CHD imposes any

paperwork burden.

X. Effective Date

FDA is proposing to make these regulations effective upon

publication of a final rule based on this proposal.

XI. Comments

Interested persons may, on or before August 5, 1997, submit to the

Dockets Management Branch (address above) written comments regarding

this proposal. Two copies of any comments are to be submitted, except

that individuals may submit one copy. Comments are to be identified

with the docket number found in brackets in the heading of this

document. Received comments may be seen in the office above between 9

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

XII. 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., ``Petition for Health Claim--Soluble Fiber from

Psyllium and Coronary Heart Disease,'' June 12, 1996 [CP1].

2. Scarbrough, F. Edward, Center for Food Safety and Applied

Nutrition, FDA, Letter to Richard M. Clark, Kellogg Co., September

18, 1996.

3. DHHS, 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. DHHS, PHS and the National Institutes of Health, ``National

Cholesterol Education Program: Population Panel Report,'' Bethesda,

MD, pp. 1-40, 1990.

6. Sempos, C. T., J. I. Cleeman, M. D. Carroll, C. L. Johnson,

P. S. Bachorik, D. J. Gordon, V. L. Burt, R. R. Briefel, C. D.

Brown, K. Lippel, and B. M. Rifkind, ``Prevalence of High Blood

Cholesterol Among U.S. Adults. An Update Based on Guidelines From

the Second Report of the National Cholesterol Education Program

Adult Treatment Panel,'' Journal of the American Medical

Association, 269:3009-3014, 1993.

7. LSRO, FASEB, ``Physiological Effects and Health Consequences

of Dietary Fiber,'' Bethesda, MD, 1987.

8. LSRO, FASEB, ``Evaluation of Publicly Available Scientific

Evidence Regarding Certain Nutrient-Disease Relationships: 6.

Dietary Fiber and Cardiovascular Disease,'' Bethesda, MD, 1991.

9. 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.

10. 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.

11. Anderson, J. W, T. L. Floore, P. B. Geil, D. Spencer, and T.

K. Balm, ``Hypercholesterolemic 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.

12. 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.

13. 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,'' Unpublished,

1994.

14. 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, 261:3419-3423, 1989.

15. Davidson, M. H., ``Long-term Influence of Psyllium-enriched

Foods on Serum Lipids among Subjects with Hypercholesterolemia

Consuming a Low Fat Diet,'' Unpublished study, 1996.

16. 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.

17. 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.

18. Keane, W. F., V. T. Miller, L. P. Bell, C. E. Halstenson, L.

D. Allgood, H. Tully, 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.

19. 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.

20. Neal, G. W. and T. K. Balm, ``Synergistic Effects of

Psyllium in the Dietary Treatment of Hypercholesterolemia,''

Southern Medical Journal, 83:1131-1137, 1990.

21. Schectman, G., J. Hiatt, 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.

22. 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.

23. Stoy, D. B., J. C. LaRosa, B. K. Brewer, M. Mackey, R. A.

Muesing, ``Cholesterol-lowering Effects of Ready-to-eat Cereal

Containing Psyllium,'' Journal of the American Dietetic Association,

93:910-912, 1993.

24. Stoy, D. B., J. C. LaRosa, B. K. Brewer, L. G. Saldhanda, R.

A. Muesing, ``Lipid Lowering Effects of Ready-to-eat Cereal

Containing Psyllium: a Randomized Crossover Trial,'' Unpublished,

1993.

25. Summerbell, C. D., P. Manley, D. Barnes, and A. Leeds, ``The

Effects of Psyllium on Blood Lipids in Hypercholesterolemic

Subjects,'' Journal of Human Nutrition and Dietetics, 7:147-151,

1994.

26. Weingand, K. W., N-A. Le, B. R. Kuzmak, W. V. Brown, B. P.

Daggy, T. A.

[[Page 28243]]

Miettinen, B. V. Howard, and W. J. Howard, ``Effects of Psyllium on

Cholesterol and Low-density Lipoprotein Metabolism in Subjects with

Hypercholesterolemia,'' Unpublished, no date.

27. 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.

28. 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.

29. Lee, S. C., E. Farmakalidis, and L. Prosky, ``Determination

of Soluble and Insoluble Dietary Fiber in Psyllium-containing Cereal

Products,'' Journal of the AOAC International, 78:724-729, 1995.

30. Jenkins, D. J. A., S. Mueller, T. M. S. Wolever, V. Rao, T.

Ransom, D. Boctor, P. Spadafor, C. Mehling, L. K. Relle, E. Chow, K.

MacMillan, and V. Fulgoni, ``High Soluble Fiber Foods Reduce Serum

Lipids Even When Diets Are Already Low in Saturated Fat and

Cholesterol,'' Unpublished study, 1992.

31. LSRO, ``The Evaluation of the Safety of Using Psyllium Seed

Husk as a Food Ingredient,'' Bethesda, MD, December 1993.

32. James, J. M., S. K. Cooke, A. Barnett, and H. A. Sampson,

``Anaphylactic Reactions to a Psyllium-containing Cereal,'' Journal

of Allergy and Clinical Immunology, 88:402-408, 1991.

33. Ross, R., ``Atherosclerosis,'' in Cecil - Textbook of

Medicine, J. B. Wyngaarden, L. H. Smith, and J. C. Bennett, editors,

Harcourt Brace Jovanevich, Inc., Philadelphia, p. 293, 1992.

34. USP, ``The National Formulary,'' US Parmacopeial Convention,

Inc., Rockville, MD, UPS 23, NF 18, p. 1341, 1995.

35. Saltsman, J., Memo to file with Table 1: ``Summary of

clinical trials: psyllium and CHD,'' and Table 2: ``Psyllium and

CHD,'' January 28, 1997.

36. Goodlad, R. A., B. Ratcliffe, C. Y. Lee, and N. A. Wright,

``Dietary Fibre and the Gastrointestinal Tract: Differing Trophic

Effects on Muscle and Mucosa of the Stomach, Small Intestine, and

Colon,'' European Journal of Clinical Nutrition, 49(Suppl. 3):S178-

S181, 1995.

37. Wasan, H. S. and R. A. Goodlad, ``Fibre-supplemented Foods

May Damage Your Health, Lancet, 348:319-320, 1996.

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, it is

proposed that 21 CFR part 101 be amended as follows:

PART 101--FOOD LABELING

1. The authority citation for 21 CFR part 101 continues to read as

follows:

Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act

(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of

the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342,

343, 348, 371).

2. Section 101.81 is amended by revising the section heading, the

heading for paragraphs (a) and (b), and paragraphs (a)(3), (b)(2),

(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), and by adding paragraph

(c)(2)(ii)(B) 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

less than 300 mg 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) * * *

(2) * * *

(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.

(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 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 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

[[Page 28244]]

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 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 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

the food product], as part of a diet low in saturated fat and

cholesterol, may reduce the risk of heart disease.

(2) Diets low in saturated fat and cholesterol that include soluble

fiber 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.

Dated: May 15, 1997.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97-13379 Filed 5-21-97; 8:45 am]

BILLING CODE 4160-01-F

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

----------------------------------------------------------------------------------------------------------------

Supplements

(Psyllium, Diet Intake Magnitude of

Study Duration Treatment Number of Placebo) of groups: Magnitude of Placebo

Subjects Soluble Fiber Sat fat % E; PSY Effect* Effect

g/d CHOL mg/d

----------------------------------------------------------------------------------------------------------------

Levin et Base: 8-wk Step 1; Tx: 16- PSY: 30 (26 10.2 g/d bulk Sat fat: PSY- CHOL: -13 mg/ CHOL: 0; LDL-

al. wk Step 1+supplement men) laxative, 6.7%; C- dL (5.6%) C -2.2%; HDL-

(Ref. 19) Pla: 28 (23 cellulose 6.3% LDL-C: -13 mg/ C:

men) PSY: CHOL: PSY- dL (8.6%)

166 mg; C- +6% (sig

7 g SF 135 mg from PSY)

Bell et Base: 12-wk Step 1; Tx: 8- PSY: 40 (20 10.2 g/d bulk Sat fat: PSY- CHOL: -9 mg/ CHOL: 0; LDL-

al. wk Step 1+supplement men) laxative, 8-10%; C- dL (4.2%) C -0.2%; HDL-

(Ref. 14) Pla: 35 (18 cellulose 7.7-8.6% LDL-C: -12 mg/ C no sig dif

men) PSY: CHOL: PSY- dL (7.7%) (grps)

168 mg; C-

7 g SF 206 mg

Davidson Base: 8-wk Step 1; Tx: 24- PSY 1 56 (31 3.4 g, 6.8 g, Sat fat: PSY- CHOL: -3% CHOL: +1.7%;

et al. wk Step 1 + PSY or men) 10.2 g/d; 7-8.6%; C- 7- (PSY 3) LDL-C: +3%

(Ref. 15) control food (3 servings/ PSY 2 40 (24 incorporated 8.6% LDL-C: -5% HDL-C: No sig

d) men) into foods: CHOL: PSY 1- (PSY 3) dif (grps)

PSY 3 43 (28 C foods: no 151 mg; PSY

men) PSY 2- 181; PSY

C 59 PSY 1: 3- 169C- 145

mg

2.3 g SF,

PSY 2:

.6 g;

PSY 3:

7 g

Everson Regular diet; 5-d Base; 2 20 men 15.3 g/d bulk Sat fat: PSY- CHOL: -14 mg/ CHOL: -1.9%;

et al. 40-d periods; 11-d laxative, 12%; C- 13.2 dL (-5%) LDL-C: -2.7%

(Ref. 16) washout; crossover cellulose % LDL-C: -15 mg/ HDL-C: No sig

PSY: CHOL: PSY- dL (8%) dif (grps)

296 mg; C-

10 g SF 274 mg

Jenkins Base: 2-mo Step 2; Tx: 2 1- 12 Ss (3m/9f) Mean intake: Sat fat: 4% CHOL: -16.6 HDL-C: No sig

et al. mo Step 2 metabolic 9.35 g/d PSY all grps mg/dL dif (grps)

(Ref. 30) diets, crossover, washout in cereal PSY: 36 mg; Tx

PSY: 6.8 g SF C: 29 mg difference:

CHOL PSY- 36 3.4%

mg; C-29 mg LDL-C: -9.3

mg/dL

Tx

difference:

5.1%

Stoy et 4-wk Step 1; Step 1 + 23 men Estimated Sat fat: PSY: CHOL: -10 mg/ HDL-C: No sig

al. (8x5x5 wks): Grp 1: PSY- 11.6 g/d PSY 5.1% (Grp 1) dL (4%) dif (grps)

(Ref. 23) Pla-PSY; Grp 2: Pla-PSY- from cereal: and 5.1% LDL-C: -11 mg/

Pla (Grp 2) dL (6%)

8 g SF; Wheat: 4.5%

Wheat (Grp 1) and

cereal: 5.0% (Grp 2)

CHOL: PSY 141-

3 g SF 165 mg

Wheat: 164 mg

(Grp 1), 117-

170 (Grp 2)

[[Page 28245]]

Stoy et 4-wk Step 1; Step 1 + 22 men Estimated Sat fat: PSY: CHOL: -10 mg/ HDL-C: No sig

al. (8x5x5 wks): Grp 1: PSY- 11.6 g/d PSY 4.8 (Grp 1) dL (4%) dif (grps)

(Ref. 24) Pla-PSY; Grp 2: Pla-PSY- from cereal: and 5.2% LDL-C: -11 mg/

Pla (Grp 2) dL (6%)

8 g SF; Wheat: 4.7%

Wheat (Grp 1) and

cereal: 5.6% (Grp 2)

CHOL: PSY 155-

3 g SF 163 mg

Wheat: 133 mg

(Grp 1), 169-

172 (Grp 2)

----------------------------------------------------------------------------------------------------------------

* Significant differences between treatment and placebo groups unless otherwise indicated.

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

mo Months

oz Ounces

Pla Placebo

Pro Protein

PSY Psyllium

Sat fat Saturated fat

SF Soluble fiber

Sig Dif Statistically significant difference

Step 1 30% kcals fat, 55% CHO, 15% Pro, approximately

% Percent

[FR Doc. 97-13379 Filed 5-21- 97; 8:45 am]

BILLING CODE 4160-01-F