[Federal Register Volume 63, Number 32 (Wednesday, February 18, 1998)]
[Rules and Regulations]
[Pages 8103-8121]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-4074]
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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, < 10% kcals sat fat, <
300 mg cholesterol
TDF Total dietary fiber
Tx Treatment
wk Week
Approximately
% Percent
[FR Doc. 98-4074 Filed 2-12-98; 4:18 pm]
BILLING CODE 4160-01-F