[Federal Register Volume 62, Number 99 (Thursday, May 22, 1997)]
[Proposed Rules]
[Pages 28234-28245]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-13379]
Federal Register / Vol. 62, No. 99 / Thursday, May 22, 1997 /
Proposed Rules
[[Page 28234]]
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: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
authorize the use, on food labels and in food labeling, of health
claims on the association between soluble fiber from psyllium husks and
reduced risk of coronary heart disease (CHD). FDA is proposing this
action in response to a petition filed by the Kellogg Co. (the
petitioner). The agency has tentatively concluded that, based on the
totality of publicly available scientific evidence, soluble fiber from
psyllium husk, similar to beta ()-glucan soluble fiber from
whole oats, when included as part of a diet low in saturated fat and
cholesterol, may reduce the risk of CHD by lowering blood cholesterol
levels. Therefore, the agency is proposing to amend the regulation that
authorized a health claim on soluble fiber from whole oats and the risk
of CHD to include soluble fiber from psyllium husks.
DATES: Written comments by August 5, 1997. The agency is proposing that
any final rule that may issue based upon this proposal become effective
upon its publication.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Joyce J. Saltsman, Center for Food
Safety and Applied Nutrition (HFS-165), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-205-5916.
SUPPLEMENTARY INFORMATION:
I. Background
The Nutrition Labeling and Education Act of 1990
On November 8, 1990, the President signed into law the Nutrition
Labeling and Education Act of 1990 (the 1990 amendments) (Pub. L. 101-
535). This new law amended the Federal Food, Drug, and Cosmetic Act
(the act) in a number of important ways. One of the most notable
aspects of the 1990 amendments was that they confirmed FDA's authority
to regulate health claims on food labels and in food labeling.
In the Federal Register of January 6, 1993 (58 FR 2478), FDA
adopted a final rule that implemented the health claim provisions of
the act (hereinafter referred to as the 1993 health claims final rule).
In that final rule, FDA adopted Sec. 101.14 (21 CFR 101.14), which sets
out the rules for the authorization and use of health claims. The
agency also adopted Sec. 101.70 (21 CFR 101.70), which establishes a
process for petitioning the agency to authorize health claims about a
substance-disease relationship (Sec. 101.70(a)) and sets out the types
of information that any such petition must include (Sec. 101.70(d)).
These regulations became effective on May 8, 1993.
In addition, FDA conducted an extensive review of the evidence on
the 10 substance-disease relationships listed in the 1990 amendments.
As a result of its review, FDA has authorized claims that relate to 8
of these 10 relationships.
In its review of the relationship between dietary fiber and
cardiovascular disease (CVD), the agency reviewed all relevant
scientific evidence on dietary fiber and its effects on serum
cholesterol. The agency started by examining the conclusions and
recommendations of the pertinent Federal Government reviews on this
topic area: the 1988 ``Surgeon General's Report on Nutrition and
Health'' (the Surgeon General's report) (Ref. 3) and the 1989 Food and
Nutrition Board, National Academy of Sciences' (FNB/NAS) ``Diet and
Health'' (Ref. 4). These two reports (Refs. 3 and 4) provided a
comprehensive review of the role of a broad range of nutrients,
including dietary fiber, in the development of a number of chronic
diseases, including heart disease. Because the FNB/NAS and Surgeon
General's report were done independently but concurrently, taken
together, they provide an authoritative picture of the state of
scientific opinion at the time that they were published in 1988 and
1989. Therefore, the agency began its review of the dietary fiber
evidence with studies that had been published since 1988. This evidence
included studies on all fibers and did not focus on any particular
individual fibers. While the agency denied the use in food labeling of
health claims relating total dietary fiber to reduced risk of CVD (58
FR 2552), it authorized a health claim relating diets low in saturated
fat and cholesterol and high in fruits, vegetables, and grain products
that contain dietary fiber (particularly soluble fiber) to a reduced
risk of CHD, one of the most common, most frequently reported, and most
serious forms of CVD.
In denying the dietary fiber and CVD health claim, the agency
stated that it is difficult to determine the relationship between
dietary fiber and heart disease because dietary fiber is a diverse
group of chemical substances that may be associated with different
physiological functions (58 FR 2552 at 2572). Chemically and
physiologically, cellulose, lignin, hemicellulose, pectin, and alginate
(all relatively purified fiber types) behave differently. Likewise,
wheat bran, oat bran, and rice bran (all heterogeneous mixtures of
fibers) are not similar in composition. The agency also noted that it
is very difficult to chemically analyze dietary fiber components, and
that, consequently, it is hard to correlate the role of specific fiber
components to health effects.
Based on its review of numerous authoritative documents, including
Federal Government reports and recent research on dietary fiber and
CHD, and on its consideration of comments received in response to the
proposed rule entitled ``Health Claims; Dietary Fiber and
Cardiovascular Disease'' (56 FR 60582, November 27, 1991) (hereinafter
referred to as the 1991 dietary fiber and CVD proposal), FDA concluded
that the publicly available scientific evidence supported an
association between diets low in saturated fat and cholesterol and high
in fruits, vegetables, and grain products (i.e., foods that are low in
saturated fat and cholesterol and that are good sources of dietary
fiber) and reduced risk of heart disease (58 FR 2552 at 2572). The
agency further stated that, although the specific roles of the numerous
potentially protective substances in such plant foods were not yet
understood, populations with diets rich in these foods experience many
health advantages, including lower rates of heart disease. The agency
noted, however, that there was no scientific agreement as to whether
the observed protective effects against heart disease were the result
of the combination of nutrient components of the foods, including
soluble fiber; of the other components of soluble fiber-rich diets (for
example, potassium and magnesium); of the displacement of saturated fat
and cholesterol from the diet; or of nonnutritive substances in these
foods.
For all these reasons, the agency stated that the fact that these
foods contain dietary fiber, particularly soluble fiber, could serve as
a useful marker for identifying those fruits, vegetables, and grain
products that,
[[Page 28235]]
when added to diets low in saturated fat and cholesterol, may help in
reducing blood low density lipoprotein (LDL)-cholesterol levels (58 FR
2552 at 2572). Thus, the agency authorized a health claim in
Sec. 101.77 (21 CFR 101.77) on the association between diets low in
saturated fat and cholesterol and high in vegetables, fruit, and grain
products that contain soluble fiber and a reduced risk of heart
disease.
In the 1993 dietary fiber and CVD final rule, in response to a
comment regarding the apparent hypocholesterolemic properties of
specific food fibers, e.g., oats, FDA agreed that the effectiveness of
naturally occurring fibers in foods may be documented for specific food
products (e.g., oat brans meeting specified parameters) (58 FR 2552 at
2567). Further, the agency stated that if manufacturers could document,
through appropriate studies, that dietary consumption of the soluble
fiber in their particular food has the effect of lowering LDL-
cholesterol, and has no adverse effects on other heart disease risk
factors (e.g., high density lipoprotein (HDL)-cholesterol), they should
petition for a health claim for their particular product.
In the Federal Register of January 23, 1997, FDA published a final
rule on the relationship between soluble fiber from whole oats and
reduced risk of coronary heart disease (the soluble fiber from whole
oats final rule), Sec. 101.81 (21 CFR 101.81) (62 FR 3584 and modified
at 62 FR 15343, March 31, 1997). In that document, the agency concluded
that the type of soluble fiber in whole oats, -glucan soluble
fiber, is the primary component responsible for the hypocholesterolemic
properties associated with consumption of whole oat products as part of
a diet that is low in saturated fat and cholesterol (62 FR 3584 at
3585). The agency based its conclusions on the totality of publicly
available evidence, taking into account evidence showing that
consumption of -glucan soluble fiber from whole oats has the
effect of lowering blood total- and LDL-cholesterol in both humans and
animals (62 FR 3584 at 3586).
The agency also acknowledged the likelihood that consumption of
-glucan soluble fiber from sources other than whole oats, as
well as that from certain other non -glucan soluble fibers,
will affect, as part of an appropriate diet, blood lipid levels (62 FR
3584 at 3587). Although the agency considered structuring the final
rule as one on ``soluble fiber from certain foods'' and the risk of CHD
to allow flexibility in expanding the claim to other sources of soluble
fiber, it stated that it was premature to do so inasmuch as the agency
had not reviewed the totality of evidence on other, non-whole oat
sources of soluble fiber. However, FDA structured Sec. 101.81 in a way
that, while the regulation covered -glucan soluble fiber from
whole oats, would allow it to be amended as evidence becomes available
to support the use of the claim for other sources of soluble fiber.
The present rulemaking is in response to a manufacturer's health
claim petition on the relationship between soluble fiber from psyllium
and the risk of heart disease.
II. Petition for Health Claim on Psyllium and Reduced Risk of CHD
A. Background
On June 12, 1996, the Kellogg Co. submitted a petition to FDA
requesting that the agency authorize a health claim on the relationship
between consumption of soluble fiber from psyllium (specifically from
psyllium husks) and the risk of CHD (Ref. 1). On September 18, 1996,
the agency sent the petitioner a letter stating that it had completed
its initial review of the petition, and that the petition would be
filed in accordance with section 403(r)(4) of the act (21 U.S.C.
343(r)(4)) (Ref. 2). In this document, the agency will consider whether
a health claim on this nutrient-disease relationship is justified under
the standard in section 403(r)(3)(B)(i) of the act and in
Sec. 101.14(c) of FDA's regulations. The following is a review of the
health claim petition.
B. Preliminary Requirements
1. The Substance Is Associated With a Disease for Which the U.S.
Population Is at Risk
The regulations authorizing claims on dietary saturated fat and
cholesterol and risk of CHD (Sec. 101.75 (21 CFR 101.75)); fruits,
vegetables, and grain products that contain soluble fiber and risk of
CHD (Sec. 101.77); and soluble fiber from whole oats and risk of CHD
(Sec. 101.81) establish that CHD is a disease for which the U.S.
population is at risk. In adopting those regulations, FDA stated that
CHD remains a major public health problem, the number one cause of
death in the United States. Despite the decline in deaths from CHD over
the past 30 years, this disease is still exacting a tremendous toll in
morbidity and mortality (Refs. 3 through 5). There are more than
500,000 deaths each year for which CHD is an underlying cause, and
another 250,000 deaths for which CHD is a contributing cause. About 20
percent of American adults ages 20 to 74 years have blood total
cholesterol levels in the ``high'' category (total cholesterol greater
than or equal to () 240 milligrams (mg) per (/) deciliter
(dL) or LDL-cholesterol 160 mg/dL) (Ref. 6). Another 31
percent have ``borderline'' cholesterol levels (total cholesterol
between 200 to 239 mg/dL). Therefore, based on these facts as presented
in Secs. 101.75, 101.77, and 101.81, FDA tentatively concludes that the
requirement in Sec. 101.14(b)(1) has been met.
2. The Substance is a Food
Psyllium is a harvestable grain from plants of the Plantago genus
(Ref. 1, p. 5-6). Different types of psyllium are available, depending
on the growing region. It is primarily cultivated in France, Spain, and
India, with some small quantities grown in the American Southwest.
Psyllium husk (also known as psyllium seed husk), which comes from the
dried coat of the psyllium seed, is used as a food or food component in
a number of foods in the United States (Ref. 1, p. 9-11) and is the
source of psyllium soluble fiber that is the subject of the petition.
Psyllium husk is a concentrated source of soluble fiber and contributes
certain technical effects (e.g., as a stabilizer) that are retained
when it is consumed at levels necessary to justify the petitioned
claim.
Therefore, FDA tentatively concludes that the substance satisfies
the preliminary requirements of Sec. 101.14(b)(3)(i).
3. The Substance Is Safe and Lawful
The petitioner has also submitted a petition requesting that FDA
affirm that the use of psyllium husk in grain-based foods is generally
recognized as safe (GRAS) (55 FR 4481, February 8, 1990). The agency
notes that this GRAS affirmation petition (GRASP 0G0357) is still under
review, and that authorization of a health claim should not be
interpreted as affirmation that the petitioned uses of psyllium are
GRAS. Such a determination can be made only after the agency has
completed its review of the GRAS petition. A preliminary review of the
GRAS affirmation petition, however, reveals that it contains
significant evidence supporting the safety of the use of this substance
at the levels necessary to justify a health claim.
In its GRAS affirmation petition, the petitioner relied heavily on
the conclusions about the safety of psyllium by the Life Sciences
Research Office (LSRO) of the Federation of American Societies for
Experimental Biology (FASEB) (Ref. 1, pp. 12-17). In its 1993 report
entitled ``The Evaluation of the Safety of Using Psyllium Husk as a
Food Ingredient,'' LSRO reviewed and
[[Page 28236]]
evaluated published data, unpublished studies that were in press at
that time, and other information and data. Based on this review, LSRO
concluded that:
There is no evidence in the available information on psyllium
that demonstrates or suggests reasonable grounds to suspect a hazard
to the public when it is used in a number of food categories and at
levels of addition that would result in total consumption of as much
as 25 g/day of psyllium. However, it is not possible to determine
without additional data whether a significant increase in
consumption above 20 to 25 g/day would constitute a dietary hazard.
(Ref. 31, p. 57.) The agency is not prepared to disagree with LSRO's
conclusions on the safety of psyllium husk.
The agency points out, however, that some concerns about the safety
of psyllium do exist. For example, available information suggests that
long-term exposure to high levels of psyllium husk may enhance
epithelial cell proliferation in the gastrointestinal tract. Rats
consuming an elemental diet containing 30 percent fiber supplement, of
which 10 percent was Ispaghula (psyllium), had increased cell
proliferation in the stomach, distal small intestine, and colon when
compared to rats consuming an elemental diet with no fiber supplement
(Ref. 36). There is no agreement in the scientific community, however,
whether such an increase in cell proliferation is related to an adverse
health effect (Ref. 37). FDA requests comments on whether enhanced
proliferation of gastrointestinal tract epithelial cells as a result of
long-term exposure to psyllium husk is of concern, and whether it would
provide a basis for not authorizing a claim.
The agency is also aware that psyllium husk can cause allergic
reactions in some people, such as health care professionals, who
regularly dispense psyllium containing products in the course of their
work. Information provided by the petitioner (Ref. 32) shows that there
are at least 13 protein fractions present in psyllium husk
preparations. Some of these protein fractions cross react with sera
obtained from individuals who experienced allergic reactions to
psyllium-containing foods. The information also shows that refinement
of psyllium husk preparations, i.e., increasing the purity of psyllium
husk, by mechanical sieving can reduce the level of antigenic protein
fractions (Ref. 32).
Because of concerns regarding the allergenic potential of products
derived from psyllium seed, FDA is proposing specifications for the
purity of the psyllium husk that is the subject of this health claim
proposal to reduce the potential for allergic reactions to foods
containing added psyllium. These specifications are based on
information provided in the petition (Ref. 32) and on the
specifications used by the petitioner (Ref. 1). FDA requests comments
on the adequacy of these proposed specifications to reduce the
allergenic potential of psyllium husk consumed as a component of food.
Are other steps, such as requiring that a psyllium-containing product
that bears a health claim declare on its prinicipal display panel that
psyllium is present in the food, necessary?
Additionally, the agency is aware of the potential for
gastrointestinal obstruction to occur following consumption of psyllium
husk in the absence of sufficient liquid to ensure thorough hydration.
However, the 1993 report by LSRO noted that reports of gastrointestinal
obstruction have been associated almost exclusively with consumption of
bulk laxatives without proper hydration (Ref. 31). Moreover, LSRO
stated that there have been no such reports associated with the
consumption of psyllium-containing cereals consumed with milk. It also
noted that there are no data regarding possible alimentary tract
obstruction that could be associated with consumption of psyllium-
containing products such as poptarts, waffles, breads, and other foods
that may be consumed without a liquid (Ref. 31). LSRO stated that the
moderate amount of psyllium in these products would not be expected to
cause gastrointestinal obstruction, and that any such possibility would
be reduced by a suitable suggestion that these products be consumed
with fluids (Ref. 31). The agency is asking for comments on whether
psyllium-containing foods should carry a statement advising that the
product be consumed with liquids, or whether the potential for blockage
is not an issue of concern for psyllium-containing food.
Based on the totality of the evidence, the agency is not prepared,
at this time, to take issue with the petitioner's view that the use of
psyllium husk is safe and lawful. Although FDA tentatively concludes
that the petitioner has provided evidence that satisfies the
requirement in Sec. 101.14(b)(3)(ii) that use of psyllium husk at the
levels necessary to justify a claim is safe and lawful, the agency
requests comment on this tentative conclusion. The agency recognizes
that, should this proposed health claim be authorized, there may be an
increase in the consumption of psyllium. Therefore, the agency also
requests comments on actions, if any, that may be necessary to ensure
that longterm consumption of psyllium will be at safe levels, such as
establishing a maximum psyllium content that foods may contain to bear
the health claim or limiting the kinds of foods that can contain
psyllium and bear a claim.
III. Review of Scientific Evidence
A. Basis for Evaluating the Relationship Between Soluble Fiber from
Psyllium and CHD
In the 1991 dietary fiber and CVD proposal, the agency set forth
the basis for the relationship between dietary fiber and CVD (56 FR
60582 at 60583). In that document, the agency stated that there are
many risk factors that contribute to the development of CVD, and
specifically CHD, one of the most serious forms of CVD and the leading
cause of disability. The agency also stated that there is general
agreement that elevated blood cholesterol levels are one of the major
``modifiable'' risk factors in the development of CVD and, more
specifically, CHD.
The Federal Government and others who have reviewed the matter have
concluded that there is substantial epidemiologic evidence that high
blood levels of total cholesterol and LDL-cholesterol are a cause of
atherosclerosis (inadequate circulation of blood to the heart due to
narrowing of the arteries) and represent major contributors to CHD (56
FR 60582 at 60583, Refs. 3 through 5). Factors that decrease total
cholesterol and LDL-cholesterol will also tend to decrease the risk of
CHD. High intakes of saturated fat and, to a lesser degree, of dietary
cholesterol are associated with elevated blood total and LDL-
cholesterol levels (56 FR 60727 at 60728, November 27, 1991). Thus, it
is generally accepted that blood total cholesterol and LDL-cholesterol
levels can influence the risk of developing CHD, and, therefore, that
dietary factors affecting blood total cholesterol levels affect the
risk of CHD (Refs. 3 through 5).
When considering the effect that the diet or components of the diet
have on blood (or serum) lipids, it is also important to consider the
effect that these factors may have on blood levels of high density
lipoprotein-cholesterol (HDL-cholesterol). HDL-cholesterol is involved
in the regulation of cholesterol transport out of cells and to the
liver, from which it is ultimately excreted (Refs. 3 and 33).
Therefore, HDL-cholesterol has a protective effect in the body by
helping to reduce the risk of CHD.
[[Page 28237]]
For these reasons, FDA limited its review of the relationship
between soluble fiber from the psyllium husk, hereinafter referred to
as ``psyllium,'' and CHD to effects of dietary intake of this substance
on blood lipid levels and on the risk of developing CHD. The agency
based its evaluation of the relationship between consumption of this
substance and CHD on changes in blood total cholesterol, LDL-
cholesterol, and HDL-cholesterol, resulting from dietary intervention
with soluble fiber from psyllium and with psyllium-containing products.
This focus is consistent with that used by the agency in response to
the 1990 amendments in deciding on the dietary saturated fat and
cholesterol and CHD health claim, Sec. 101.75 (56 FR 60727 and 58 FR
2739); the fruits, vegetables, and grain products and CHD claim,
Sec. 101.77 (56 FR 60582 and 58 FR 2552); and the soluble fiber from
whole oats and CHD claim, Sec. 101.81 (61 FR 296 and 62 FR 3584).
B. Review of Scientific Evidence
1. Evidence Considered in Reaching the Decision
The petitioner submitted scientific studies evaluating the
relationship between soluble fiber from psyllium, consumed as a food
and as an ingredient in foods, and serum lipid levels (Ref. 1). These
studies were conducted between 1965 and 1996. The petition included
tables that summarized the outcome of those studies and a summary of
the evidence. Consistent with the approach taken in the dietary fiber/
CVD proposed rules, the agency began its review by considering those
psyllium studies that were published since 1988 (date of publication of
the Surgeon General's report). In addition, in its review of the
petition, the agency considered the conclusions of two LSRO reports
(Refs. 7 and 8) relative to studies involving psyllium.
2. Criteria for Selection of Human Studies
The criteria that the agency used to select pertinent studies were
that the studies: (1) Present data and adequate descriptions of the
study design and methods; (2) be available in English; (3) include
estimates of, or enough information to estimate, soluble dietary fiber
intakes; (4) include direct measurement of blood total cholesterol and
other blood lipids related to CHD; and (5) be conducted in persons who
represent the general U.S. population (adults with blood total
cholesterol levels less than (<) 300="" mg/dl).="" in="" selecting="" human="" studies="" for="" review,="" the="" agency="" excluded="" studies="" that="" were="" published="" in="" abstract="" form="" because="" they="" lacked="" sufficient="" detail="" on="" study="" design="" and="" methodologies,="" and="" because="" they="" lacked="" necessary="" primary="" data.="" studies="" using="" special="" population="" groups,="" such="" as="" insulin-dependent="" diabetics,="" individuals="" with="" very="" high="" serum="" cholesterol="" (mean="" greater="" than="" 300="" mg/dl),="" individuals="" taking="" lipid-="" lowering="" medication="" during="" treatment="" periods,="" children="" with="" hypercholesterolemia,="" and="" persons="" who="" had="" already="" experienced="" a="" myocardial="" infarction,="" were="" excluded="" because="" of="" questions="" about="" their="" relevance="" to="" the="" general="" healthy="" u.s.="" population.="" studies="" in="" which="" psyllium="" was="" tested="" as="" part="" of="" a="" mixture="" of="" other="" soluble="" fibers,="" e.g.,="" oat="" bran,="" were="" also="" excluded="" from="" review="" because="" it="" was="" not="" possible="" to="" evaluate="" the="" influence="" of="" psyllium="" alone="" on="" risk="" factors="" for="" heart="" disease.="" these="" criteria="" are="" consistent="" with="" those="" that="" the="" agency="" used="" to="" evaluate="" the="" relationship="" between="" other="" substances="" and="" chd.="" 3.="" criteria="" for="" evaluating="" the="" relationship="" between="" soluble="" fiber="" from="" psyllium="" and="" chd="" fda="" generally="" applied="" the="" same="" criteria="" in="" evaluating="" studies="" on="" the="" relationship="" between="" soluble="" fiber="" from="" psyllium="" and="" chd="" that="" it="" used="" in="" evaluating="" studies="" on="" the="" relationship="" between="" dietary="" fiber="" and="" cvd="" in="" the="" 1991="" proposed="" rule="" (56="" fr="" 60582="" at="" 60587)="" and="" in="" the="" january="" 1996="" proposed="" rule="" on="" whole="" oats="" and="" chd="" (61="" fr="" 296).="" the="" criteria="" that="" the="" agency="" used="" in="" evaluating="" the="" studies="" for="" this="" rulemaking="" include:="" (1)="" reliability="" and="" accuracy="" of="" the="" methods="" used="" in="" nutrient="" intake="" analysis,="" including="" measurements="" of="" total="" dietary="" soluble="" fiber="" and="" total="" dietary="" fiber;="" (2)="" estimates="" of="" intake="" of="" saturated="" fat="" and="" cholesterol;="" (3)="" available="" information="" on="" the="" soluble="" fiber="" content="" of="" the="" psyllium="" test="" products="" and="" control="" food;="" (4)="" measurement="" of="" study="" endpoints="" (i.e.,="" total="" cholesterol,="" ldl-="" cholesterol,="" and="" hdl-cholesterol);="" and="" (5)="" general="" study="" design="" characteristics.="" the="" general="" study="" design="" characteristics="" for="" which="" the="" agency="" looked="" included="" randomization="" of="" subjects,="" appropriateness="" of="" controls,="" selection="" criteria="" for="" subjects,="" attrition="" rates="" (including="" reasons="" for="" attrition),="" potential="" for="" misclassification="" of="" individuals="" with="" regard="" to="" dietary="" intakes,="" presence="" of="" recall="" bias="" and="" interviewer="" bias,="" recognition="" and="" control="" of="" confounding="" factors="" (for="" example,="" monitoring="" body="" weight="" and="" control="" of="" weight="" loss),="" appropriateness="" of="" statistical="" tests="" and="" comparisons,="" and="" statistical="" power="" of="" the="" studies.="" the="" agency="" considered="" whether="" the="" intervention="" studies="" that="" it="" evaluated="" had="" been="" of="" long="" enough="" duration="" to="" reasonably="" ensure="" stabilization="" of="" blood="" lipids="" (greater="" than="" or="" equal="" to="" 3="" weeks="" duration).="" finally,="" the="" agency="" considered="" it="" highly="" desirable="" if="" the="" available="" information="" on="" a="" study="" included="" information="" on="" total="" dietary="" soluble="" fiber="" content="" of="" baseline,="" treatment,="" and="" control="" diets="" and="" on="" the="" nutrient="" intakes="" of="" the="" subjects="" during="" the="" course="" of="" the="" study.="" c.="" review="" of="" human="" studies="" fda="" has="" done="" a="" comprehensive="" review="" of="" 21="" human="" studies="" on="" psyllium="" (refs.="" 9="" through="" 28="" and="" 30)="" that="" were="" submitted="" with="" the="" petition="" and="" met="" the="" forementioned="" criteria="" for="" selection="" (ref.="" 35).="" of="" these,="" the="" agency="" gave="" particular="" weight="" to="" seven="" studies="" (table="" 1="" of="" this="" document)="" (refs.="" 14,="" 15,="" 16,="" 19,="" 23,="" 24,="" and="" 30)="" that="" were="" well="" controlled,="" reported="" intakes="" of="" saturated="" fat="" and="" cholesterol,="" and="" avoided="" problems="" associated="" with="" small="" sample="" size,="" lack="" of="" placebo="" control,="" lack="" of="" blinding,="" and="" other="" design="" problems.="" the="" studies="" listed="" in="" table="" 1="" also="" had="" run-in="" periods="" of="" 4="" or="" more="" weeks="" duration="" before="" the="" treatment="" period.="" during="" the="" run-in="" period,="" subjects="" consumed="" a="" low="" saturated="" fat="" and="" cholesterol="" diet="" without="" psyllium="" or="" placebo="" to="" allow="" time="" for="" serum="" lipid="" levels="" to="" stabilize="" to="" the="" change="" in="" dietary="" intake.="" three="" of="" the="" studies="" in="" table="" 1="" were="" randomized,="" double="" blind,="" placebo-controlled,="" parallel="" trials="" (refs.="" 14,="" 15,="" and="" 19).="" one="" study="" was="" a="" randomized,="" double="" blind,="" placebo-controlled,="" crossover="" trial="" (ref.="" 16),="" and="" three="" studies="" were="" randomized,="" single="" blind,="" placebo-controlled,="" crossover="" trials="" (refs.="" 23,="" 24,="" and="" 30).="" five="" of="" the="" studies="" (refs.="" 14,="" 15,="" 19,="" 23,="" and="" 24)="" in="" table="" 1="" evaluated="" the="" effect="" of="" psyllium="" on="" serum="" lipid="" levels="" in="" subjects="" consuming="" a="" step="" 1="" diet="" (ref.="" 5)="" (i.e.,="" a="" diet="" with="" no="" more="" than="" 30="" percent="" of="" calories="" from="" total="" fat,="" less="" than="" 10="" percent="" calories="" from="" saturated="" fat,="" and="" less="" than="" 300="" mg="" cholesterol="" daily,)="" and="" one="" study="" (ref.="" 30)="" included="" psyllium="" as="" part="" of="" a="" step="" 2="" diet="" (i.e.,="" a="" diet="" with="" no="" more="" than="" 30="" percent="" of="" calories="" from="" total="" fat,=""><7 percent="" of="" calories="" from="" saturated="" fat,="" and=""><200 mg/day="" (d)="" cholesterol).="" one="" study="" (ref.="" 16)="" evaluated="" the="" effects="" of="" psyllium="" in="" subjects="" consuming="" their="" usual="" diets.="" the="" source="" of="" psyllium="" in="" three="" studies="" (refs.="" 14,="" 16,="" and="" 19)="" was="" a="" bulk="" laxative.="" subjects="" mixed="" the="" psyllium="" with="" a="" liquid="" (usually="" water)="" and="" consumed="" it="" before="" meals.="" the="" placebo="" in="" these="" studies="" was="" cellulose.="" four="" studies="" (refs.="" 15,="" 23,="" 24,="" and="" 30)="" incorporated="" psyllium="" into="" breakfast="" cereals="" or="" a="" variety="" of="" foods="" (e.g.,="" breads,="" [[page="" 28238]]="" cereal,="" pasta).="" in="" these="" studies,="" the="" placebo="" controls="" were="" the="" same="" or="" similar="" foods="" that="" did="" not="" contain="" psyllium="" (e.g.,="" breads,="" cereal,="" pasta).="" the="" level="" of="" psyllium="" consumed="" in="" the="" 7="" studies="" ranged="" from="" 3.4="" grams="" (g)/d="" (about="" 2.6="" g/d="" soluble="" fiber)="" (ref.="" 15)="" to="" about="" 11.6="" g/d="" (an="" estimated="" 8="" g/d="" soluble="" fiber)="" (refs.="" 23="" and="" 24).="" the="" duration="" of="" the="" treatment="" periods="" ranged="" from="" 4="" weeks="" (ref.="" 30)="" up="" to="" 24="" weeks="" (ref.="" 15).="" the="" male="" and="" female="" subjects="" in="" the="" 7="" studies="" were="" moderately="" hypercholesterolemic="" and="" ranged="" in="" age="" from="" 20="" to="" 80="" years.="" the="" results="" of="" the="" studies="" that="" evaluated="" psyllium="" as="" a="" supplement="" to="" the="" diet="" (refs.="" 14,="" 16,="" and="" 19)="" demonstrated="" that="" the="" subjects="" consuming="" psyllium="" daily="" experienced="" significant="" decreases="" in="" blood="" total="" cholesterol="" of="" about="" 4="" percent="" (refs.="" 14="" and="" 16)="" and="" 5="" percent="" (ref.="" 19)="" compared="" to="" the="" control="" group,="" which="" consumed="" a="" placebo.="" ldl-="" cholesterol="" decreased="" significantly,="" from="" about="" 5="" percent="" (ref.="" 16)="" to="" about="" 7="" percent="" (ref.="" 14),="" compared="" to="" the="" placebo="" control.="" in="" these="" three="" studies,="" the="" psyllium="" group="" consumed="" 10.2="" g/d="" psyllium="" (about="" 7="" g/d="" soluble="" fiber)="" (refs.="" 14="" and="" 19)="" or="" 15.3="" g/d="" (about="" 10="" g/d="" soluble="" fiber)="" (ref.="" 16).="" one="" study="" evaluated="" the="" effect="" of="" 3="" levels="" of="" psyllium="" intake="" from="" foods="" on="" lipid="" levels="" in="" hypercholesterolemic="" men="" and="" women="" (ref.="" 15).="" three="" groups="" (group="" 1,="" 2,="" and="" 3)="" consumed="" a="" variety="" of="" foods="" (cereal,="" bread,="" pasta,="" and="" snack="" bars)="" that="" provided="" 3.4="" g,="" 6.8="" g,="" or="" 10.2="" g/d="" psyllium="" (groups="" 1,="" 2,="" and="" 3,="" respectively)="" as="" part="" of="" a="" step="" 1="" diet="" for="" 24="" weeks.="" a="" control="" group="" consumed="" the="" same="" foods="" with="" no="" psyllium.="" blood="" total="" cholesterol="" was="" significantly="" lowered="" only="" in="" group="" 3="" from="" 2="" to="" 4="" percent="" compared="" to="" the="" control="" group.="" ldl-cholesterol="" decreased="" significantly="" in="" groups="" 1="" and="" 3="" (i.e.,="" about="" 5="" percent)="" compared="" to="" the="" control="" group.="" the="" total="" soluble="" fiber="" intakes="" for="" the="" control="" and="" groups="" 1,="" 2,="" and="" 3="" were="" 7="" g,="" 10="" g,="" 10.6="" g,="" and="" 12.4="" g/d,="" respectively.="" the="" authors="" stated="" that="" the="" difference="" in="" soluble="" fiber="" intake="" among="" the="" psyllium="" groups="" was="" less="" than="" expected="" and="" suggested="" that="" the="" subjects="" may="" have="" partially="" substituted="" psyllium-containing="" foods="" for="" other="" foods="" containing="" soluble="" fiber.="" the="" results="" of="" this="" study="" suggest="" that="" there="" is="" a="" dose-response="" relationship="" between="" psyllium="" intake="" and="" significant="" reductions="" in="" chd="" risk="" factors,="" but="" no="" specific="" level="" can="" be="" determined="" from="" these="" data="" because="" of="" possible="" problems="" with="" subject="" compliance="" in="" groups="" 1="" and="" 2.="" the="" results="" of="" three="" other="" studies="" that="" tested="" psyllium-containing="" cereals="" (refs.="" 23,="" 24,="" and="" 30)="" showed="" significant="" reductions="" in="" both="" blood="" total="" cholesterol="" (about="" 4="" to="" 8="" percent)="" and="" ldl-cholesterol="" (about="" 5="" to="" 10="" percent)="" compared="" to="" the="" placebo="" control.="" the="" subjects="" in="" these="" studies="" consumed="" 9.3="" g/d="" psyllium="" (about="" 6.8="" g="" soluble="" fiber)="" (ref.="" 30)="" and="" 11="" g/d="" psyllium="" (about="" 8="" g="" soluble="" fiber)="" (refs.="" 23="" and="" 24).="" there="" were="" no="" statistically="" significant="" differences="" between="" the="" psyllium="" and="" placebo="" groups="" in="" hdl-cholesterol="" in="" all="" but="" one="" of="" the="" studies="" in="" table="" 1.="" in="" the="" one="" study="" (ref.="" 19),="" post-treatment="" hdl-="" cholesterol="" was="" significantly="" higher="" in="" the="" placebo="" group="" compared="" to="" the="" psyllium="" group.="" in="" summary,="" based="" on="" the="" totality="" of="" the="" evidence="" presented="" in="" randomized="" studies,="" consumption="" of="" psyllium="" helped="" to="" reduce="" the="" levels="" of="" blood="" total="" and="" ldl-cholesterol,="" and="" thus="" the="" risk="" of="" chd,="" in="" subjects="" with="" moderately="" elevated="" to="" high="" blood="" total="" cholesterol="" who="" consumed="" either="" a="" step="" 1="" or="" step="" 2="" diet="" (low="" saturated="" fat="" and="" cholesterol)="" or="" their="" usual="" diets.="" psyllium="" did="" not="" adversely="" affect="" hdl-cholesterol="" levels.="" iv.="" decision="" to="" propose="" a="" health="" claim="" relating="" soluble="" fiber="" from="" psyllium="" to="" reduction="" in="" risk="" of="" chd="" the="" results="" of="" 7="" clinical="" trials="" with="" psyllium="" that="" were="" published="" between="" 1988="" and="" 1996="" (table="" 1),="" as="" discussed="" in="" section="" iii.c,="" above,="" consistently="" supported="" that="" there="" is="" a="" relationship="" between="" consumption="" of="" soluble="" fiber="" from="" psyllium,="" as="" part="" of="" a="" diet="" that="" is="" low="" in="" saturated="" fat="" and="" cholesterol,="" and="" reduced="" blood="" cholesterol="" levels,="" which="" in="" turn="" may="" reduce="" the="" risk="" of="" heart="" disease.="" based="" on="" this="" evidence,="" fda="" has="" tentatively="" concluded="" that="" there="" is="" significant="" scientific="" agreement="" that="" the="" available="" evidence="" supports="" that="" this="" nutrient/disease="" relationship="" is="" valid.="" thus,="" the="" agency="" is="" proposing="" to="" authorize="" health="" claims="" on="" the="" relationship="" between="" soluble="" fiber="" from="" psyllium="" and="" reduced="" risk="" of="" chd.="" fda="" points="" out,="" however,="" that="" in="" preparing="" this="" document,="" as="" is="" its="" regular="" practice="" in="" health="" claim="" proceedings,="" the="" agency="" conferred="" with="" other="" public="" health="" service="" (phs)="" agencies="" with="" relevant="" expertise.="" these="" agencies="" have="" raised="" issues="" that="" merit="" consideration="" in="" this="" rulemaking.="" first,="" in="" the="" seven="" studies="" that="" met="" the="" criteria="" for="" evaluation,="" three="" involved="" administration="" of="" psyllium="" in="" the="" form="" of="" a="" bulk="" laxative="" (refs.="" 14,="" 16,="" and="" 19),="" and="" in="" only="" four="" of="" the="" studies="" was="" psyllium="" incorporated="" into="" foods="" (refs.="" 15,="" 23,="" 24,="" and="" 30).="" one="" phs="" agency="" raised="" an="" issue="" about="" the="" appropriateness="" of="" reliance="" on="" the="" former="" studies,="" in="" which="" psyllium="" was="" not="" consumed="" as="" an="" ingredient="" of="" conventional="" food.="" the="" agency="" has="" tentatively="" decided="" that="" reliance="" on="" references="" 14,="" 16,="" and="" 19,="" in="" which="" psyllium="" was="" administered="" in="" the="" form="" of="" a="" bulk="" laxative,="" is="" appropriate="" because="" in="" these="" studies="" the="" psyllium="" was="" fed="" at="" mealtimes,="" much="" in="" the="" manner="" of="" a="" dietary="" supplement,="" and="" in="" concentrations="" similar="" to="" those="" at="" which="" psyllium="" was="" incorporated="" into="" conventional="" foods="" in="" references="" 15,="" 23,="" 24,="" and="" 30.="" moreover,="" the="" effect="" of="" consuming="" psyllium="" on="" the="" risk="" of="" heart="" disease="" (i.e.,="" about="" 3="" to="" 5="" percent="" reductions="" in="" blood="" total="" and="" ldl-cholesterol)="" observed="" in="" the="" studies="" in="" which="" this="" substance="" was="" consumed="" in="" conventional="" food,="" e.g.,="" in="" cereal="" (refs.="" 15,="" 23,="" 24,="" and="" 30),="" was="" similar="" to="" that="" seen="" in="" the="" studies="" (refs.="" 14,="" 16,="" and="" 19)="" in="" which="" it="" was="" consumed="" as="" a="" bulk="" laxative.="" these="" results="" suggest="" that="" the="" form="" in="" which="" psyllium="" is="" consumed="" is="" not="" significant.="" however,="" the="" agency="" is="" asking="" for="" comments="" on="" whether="" it="" is="" appropriate="" to="" consider="" studies="" in="" which="" psyllium="" was="" fed="" in="" bulk="" form="" as="" evidence="" in="" evaluating="" this="" substance/="" disease="" relationship.="" second,="" the="" subject="" populations="" in="" the="" studies="" listed="" in="" table="" 1="" had="" borderline="" to="" high="" blood="" cholesterol="" levels.="" one="" phs="" agency="" questioned="" the="" relevance="" of="" these="" studies="" to="" the="" general="" population,="" which="" includes="" individuals="" with="" normal="" as="" well="" as="" elevated="" blood="" cholesterol="" levels.="" the="" agency="" has="" tentatively="" concluded="" that="" the="" hypercholesterolemic="" study="" populations="" in="" the="" studies="" listed="" in="" table="" 1="" are="" relevant="" to="" the="" general="" population="" because,="" based="" on="" data="" from="" the="" national="" health="" and="" nutrition="" examination="" surveys="" (nhanes)="" iii,="" the="" prevalence="" of="" individuals="" with="" elevated="" blood="" cholesterol="" (i.e.,="" 200="" mg/dl="" or="" greater)="" is="" high="" (approximately="" 51="" percent="" of="" adults)="" (ref.="" 6).="" the="" proportion="" of="" adults="" having="" moderately="" elevated="" blood="" cholesterol="" levels="" (i.e.,="" between="" 200="" and="" 239="" mg/dl)="" was="" estimated="" to="" be="" approximately="" 31="" percent,="" and="" the="" proportion="" of="" adults="" with="" high="" blood="" cholesterol="" levels="" (240="" mg/dl="" or="" greater)="" was="" estimated="" to="" be="" approximately="" 20="" percent="" (ref.="" 6).="" it="" is="" also="" estimated="" that="" 52="" million="" americans="" 20="" years="" of="" age="" and="" older="" would="" be="" candidates="" for="" dietary="" intervention="" to="" lower="" blood="" cholesterol="" (ref.="" 6).="" the="" agency="" considers="" the="" high="" proportion="" of="" americans="" that="" have="" elevated="" blood="" cholesterol="" levels="" (i.e.,="" 51="" percent)="" to="" make="" up="" a="" significant="" portion="" of="" the="" general="" population,="" thus="" making="" the="" subject="" population="" in="" the="" studies="" listed="" in="" table="" 1="" relevant="" to="" the="" general="" population.="" however,="" the="" [[page="" 28239]]="" agency="" is="" asking="" for="" comments="" on="" this="" issue.="" v.="" decision="" to="" propose="" to="" amend="" sec.="" 101.81="" as="" discussed="" in="" section="" i.b="" of="" this="" document,="" fda="" authorized="" a="" claim="" for="" soluble="" fiber="" from="" whole="" oats="" and="" chd="" on="" january="" 23,="" 1997="" (62="" fr="" 3584).="" in="" that="" document,="" the="" agency="" stated="" that="" it="" is="" very="" likely="" that="" soluble="" fiber="" from="" certain="" foods,="" in="" addition="" to="">-glucan
soluble fiber from whole oats, may affect serum lipid levels and thus
help to reduce the risk of CHD (62 FR 3584 at 3587). The agency further
stated that if a manufacturer can document, through appropriate human
and laboratory studies, that a soluble fiber has an effect on blood
total- and LDL-cholesterol levels, and thereby can be useful in
reducing the risk of CHD, the manufacturer may petition to amend
Sec. 101.81 to include that source of soluble fiber among the food
sources about which claims are authorized (62 FR 3584 at 3587 and
3588). The agency explained that it was necessary to evaluate each
source of soluble fiber individually because soluble fiber is a family
of very heterogeneous substances that vary greatly in their effect on
the risk of CHD.
The agency tentatively concludes that the soluble fiber in
psyllium, like -glucan soluble fiber from whole oats, when
consumed as part of a diet low in saturated fat and cholesterol, may
help to reduce the risk of heart disease, and that a health claim
describing this relationship is warranted. To this end, the agency is
proposing to amend Sec. 101.81, as discussed below, to include soluble
fiber from psyllium and to broaden the subject of the claim to
``soluble fiber from certain foods'' and risk of CHD.
As discussed in the preamble to the soluble fiber from whole oats
final rule, an umbrella regulation for ``soluble fiber from certain
foods'' and CHD will provide flexibility for the inclusion of other
food sources of soluble fiber when adequate data are provided to
demonstrate that consumption of those foods may help to reduce the risk
of heart disease (62 FR 3584 at 3588). Moreover, such an umbrella
regulation has the advantage of minimizing consumer confusion in that
the claim could not be used on the label of all foods that contain
soluble fiber. Rather, the claim will be limited to those soluble fiber
sources whose consumption has been demonstrated to have a relationship
to the risk of CHD.
VI. Description of Modifications to Sec. 101.81
A. Eligible Sources of Soluble Fiber
Section 101.81(c)(2)(ii) (``Nature of the substance. Eligible
sources of soluble fiber'') lists the types and sources of soluble
fiber that have been demonstrated to the satisfaction of FDA to have a
relationship to the risk of CHD. In Sec. 101.81(c)(2)(ii)(A), FDA lists
-glucan soluble fiber from the whole oat sources, along with
the method of analysis for -glucan soluble fiber by the
Association of Official Analytical Chemists. Section
101.81(c)(2)(ii)(A)(1) through (c)(2)(ii)(A)(3) identify the whole oat
sources that are eligible to bear the claim. FDA reserved
Sec. 101.81(c)(2)(ii)(B) for future use.
In this document, FDA is proposing to add new
Sec. 101.81(c)(2)(ii)(B) to specify psyllium husk as a source of
soluble fiber eligible to be the subject of this claim. As discussed in
section II.B.3 of this document, the agency is aware that psyllium has
been associated with allergic reactions in some people, especially in
health care professionals who dispense psyllium containing products in
the course of their work. The petitioner stated that using psyllium
with a purity of 95 percent in cereal significantly reduced the
potential for allergenic responses following consumption of psyllium-
containing food (Ref. 1, pp. 85-86). Information provided by the
petitioner showed that psyllium husk that has a purity of 95 percent
has a maximum protein content of 3 percent and total extraneous matter
not to exceed 4.9 percent (i.e., 4.5 percent or less of light
extraneous matter and 0.5 percent or less of heavy extraneous matter,
as determined by USP methods (Ref. 34)).
In this document, the agency is proposing to adopt these
specifications for psyllium husk that may be the subject of a claim.
Therefore, proposed Sec. 101.81(c)(2)(ii)(B)(1) states that ``to
qualify for this claim, psyllium husk shall have a purity of no less
than 95 percent, such that it has a 3 percent or less protein content,
4.5 percent or less of light extraneous matter, and 0.5 percent or less
of heavy extraneous matter, but in no case may the combined extraneous
matter exceed 4.9 percent, as determined by U.S. Pharmacopeia (USP)
methods'' that are incorporated by reference (Ref. 1, pp. 5-6, and Ref.
34). The agency requests comments on whether the requirements proposed
in Sec. 101.81(c)(2)(ii)(B)(1) are sufficient to reduce the potential
for allergenic responses in individuals sensitive to psyllium.
Proposed Sec. 101.81(c)(2)(ii)(B)(1) identifies psyllium husk as
the dried seed coat (epidermis) of the seed of Plantago (P) ovata,
known as blond psyllium or Indian psyllium; P. indica; or P. psyllium.
This information is consistent with that provided by the petitioner
(Ref. 1, pp. 5 and 6) and the description of psyllium husk given in the
U.S. Pharmacopeia's (USP) ``The National Formulary'' (Ref. 34).
In proposed Sec. 101.81(c)(2)(ii)(B)(2), FDA identifies the
analytical method that it intends to use to determine the amount of
soluble fiber that is provided by psyllium. Because psyllium-containing
food products are highly viscous in aqueous solutions and may not be
easily filtered, a method for analyzing for soluble and insoluble
dietary fiber from psyllium was developed by Lee et al. (Ref. 29). The
assay, a modification of method No. 991.31 from ``Official Methods of
Analysis of the Association of Official Analytical Chemists'' (AOAC),
appeared in the Journal of the AOAC International, volume 78, page 724,
1995, and FDA is proposing to incorporate it by reference in accordance
with 5 U.S.C. 552(a) and 1 CFR part 51 in this document.
B. Nature of the Food Eligible to Bear the Claim
Section 101.81(c)(2)(iii)(A) (as modified at 62 FR 15342) states
that ``the food product shall include one or more of the whole oat
foods from paragraph (c)(2)(ii) of this section, and the whole oat
foods shall contain at least 0.75 gram (g) of soluble fiber per
reference amount customarily consumed of the food'' (RACC). FDA arrived
at this amount of soluble fiber by dividing an intake of 3 g/d soluble
fiber from whole oats by 4 eating occasions per day (62 FR 3584 at
3592). The daily intake of 3 g soluble fiber was based on an analysis
of data from a dose-response study that showed that an intake of 3 g/d
-glucan soluble fiber from whole oats was associated with a
significant reduction (5 percent) in blood total- and LDL-cholesterol
levels, and the results of a meta-analysis and other oat studies (61 FR
296 at 308). Based on four eating occasions per day, each serving of
the eligible whole oat product would have to provide a minimum of 0.75
g per RACC as part of the requirements to qualify to bear the CHD
claim.
The petitioner for the psyllium claim stated that ``the
hypocholesterolemic dose-responsiveness of soluble fiber from psyllium
(i.e., psyllium husk) has not been extensively studied, but there is
evidence to suggest that the greater
[[Page 28240]]
the dose, the more pronounced the cholesterol-lowering effects will
be'' (Ref. 1, p. 100). The petitioner noted LSRO's (Ref. 7)
recommendations for soluble fiber intake for the general U.S.
population. LSRO stated that soluble fiber should account for 25 to 30
percent of the total dietary fiber intake and recommended a daily
intake of total dietary fiber intake of between 20 to 35 g/d (Ref. 7).
Based on these values, an optimal intake of soluble fiber intake would
range from 5 g/d to about 10.5 g/d.
The petitioner also reviewed the results of studies that evaluated
the effects of different intake levels of psyllium and considered the
conclusions of reviews of the literature on psyllium (Ref. 1, pp. 100
through 102). It noted that some overviews of the literature on
psyllium and serum cholesterol levels have suggested intake ranges of
10 to 30 g/d of psyllium (Ref. 1, p. 100). The petitioner also noted
that the results of the dose-response study by Davidson et al. (Ref.
15) showed that the group consuming 10.2 g/d of psyllium had
differences of approximately 4.6 percent for LDL-cholesterol and 3.3
percent for total cholesterol when compared to controls (Ref. 1, p.
101). Based on all of the evidence, the petitioner asserted that an
intake of about 7 g/d soluble fiber from 10.2 g/d psyllium may help to
reduce the risk of CHD (Ref. 1, p. 102).
The petitioner suggested that, based on a daily intake level of
10.2 g of psyllium, which provides about 7 g soluble fiber, the level
in a food to qualify to bear the CHD claim should be 2.5 g of psyllium
per RACC (10.2 g/d divided by 4 eating occasions per day), which
provides 1.7 g soluble fiber (7 g/d of soluble fiber divided by 4) per
RACC. The petitioner noted that the agency has usually assumed that
food consumption patterns generally reflect three meals and a snack (58
FR 2302 at 2379, January 3, 1993).
After review of data from studies submitted with the petition, the
agency notes that, with the exception of the dose-response study by
Davidson et al. (Ref. 15), psyllium was consumed in these studies at
levels of 10 or more g/d (soluble fiber was approximately 7 g/10 g of
psyllium) (see Table 1 and Ref. 35). In those placebo-controlled
studies that tested an intake of psyllium of 10.2 g, the effect on
serum blood lipids was consistent, i.e., blood total and LDL-
cholesterol levels were significantly lowered, and HDL-cholesterol
levels were not affected (Refs. 10, 11, 13 through 15, 18, 19, 22, and
26).
As noted earlier, Davidson et al. (Ref. 15) evaluated the effect of
psyllium at levels of 3.4 g (Group 1), 6.8 g (Group 2), and 10.2 g
(Group 3) per day from foods consumed as part of a Step 1 diet. The
results of the study showed significant lowering of serum lipids in
subjects consuming 10.2 g/d psyllium in food. The authors stated,
however, that the subjects in the first two groups may not have
complied with study protocol, thus confounding the results for them.
Because of the potential for confounding in this study, the agency
finds that the results of the Davidson study do not provide the
information needed to determine a dose-response between the level of
psyllium intake, and therefore the level of soluble fiber from
psyllium, and the degree of change in blood lipid levels.
In this document, the agency is proposing to amend Sec. 101.81 to
add soluble fiber from psyllium, but it does not have the data that
were available for -glucan soluble fiber from whole oats on
which to establish a dose-response based qualifying level for the
amount of soluble fiber from psyllium necessary for a food to be
eligible to bear the claim. As discussed above, relative to whole oat
soluble fiber qualifying levels, analysis of data from a dose-response
study showed that an intake of 3 g/d whole oat soluble fiber was
associated with a 5 percent reduction in blood lipids (61 FR 296 at
308). In the whole oat proposal, the agency explained that a
significant reduction in serum lipids of 5 percent is associated with
the level that was achieved as a result of a dietary fat and
cholesterol-focused intervention in the Multiple Risk Factor
Intervention Trial and Lipid Research Council clinical trials (61 FR
296 at 308). The agency does not have similar data from which to
determine the amount of soluble fiber from psyllium that is associated
with a 5 percent reduction in serum lipids.
In the absence of such data, the agency is tentatively proposing to
base the qualifying level of soluble fiber from psyllium on a total
daily intake of 10.2 g (about 7 g of soluble fiber), as suggested by
the petitioner. This level of intake was shown in the clinical studies
to be consistently associated with significant reductions in serum
lipids.
Therefore, FDA is proposing that the qualifying level of soluble
fiber for foods to bear this claim be 1.7 g soluble fiber from psyllium
per RACC (7 g divided by 4 eating occasions per day). The agency does
not consider it necessary to propose a qualifying amount of psyllium as
suggested in the petition (2.5 g) because the qualifying level of
soluble fiber will determine the amount of psyllium that is required.
Based on estimates from figures provided in the petition and in the
studies, psyllium is about 68 percent or more soluble fiber. Therefore,
1.7 g/RACC of soluble fiber from psyllium would relate to about 2.5 g/
RACC of psyllium husk. The agency is asking for comments on whether
this approach for establishing a qualifying soluble fiber level for
psyllium-containing products is appropriate or for data to support
another qualifying level for psyllium.
Health claims help consumers to identify those products that will
help them achieve a healthy diet (see, e.g., section 403(r)(3)(B)(iii)
of the act). Expanding Sec. 101.81 to include psyllium-containing foods
will give consumers an opportunity to select from a wider variety of
foods containing those soluble fibers that have been shown to help
reduce the risk of CHD. The availability of a variety of foods, in
turn, should help consumers increase their daily intake of soluble
fiber.
To reflect the agency's tentative decision to propose a qualifying
level of soluble fiber from psyllium that is different from that
required for whole oats, the agency is proposing to amend
Sec. 101.81(c)(2)(iii)(A) (as modified at 62 FR 15342) to set out the
qualifying level of soluble fiber from whole oat and psyllium foods.
Therefore, in this document, proposed Sec. 101.81(c)(2)(iii)(A) is
modified to state ``[T]he food product shall include:'' followed by
paragraphs (1) and (2). Paragraph (c)(2)(iii)(A)(1) is modified to
state ``one or more of the whole oat foods from paragraph (c)(2)(ii)(A)
of this section, and the whole oat foods shall contain at least 0.75
gram (g) of soluble fiber per reference amount customarily consumed of
the food product.'' FDA is proposing to state in
Sec. 101.81(c)(2)(iii)(A)(2): ``psyllium that complies with paragraph
(c)(2)(ii)(B) of this section, and the psyllium food shall contain at
least 1.7 g of soluble fiber per reference amount customarily consumed
of the food product.''
The agency recognizes that foods could be produced with a blend of
the eligible soluble fibers listed in paragraph (c)(2)(ii) and would be
willing to consider whether such foods should be eligible to bear the
health claim. An example of a product that contains a blend of the
eligible soluble fibers might be one that contains 75 percent of the
qualifying level of -glucan soluble fiber from whole oats and
25 percent of the qualifying level of soluble fiber from psyllium.
However, the agency does not have the data on which to evaluate the
relationship between consumption of foods containing both psyllium and
whole oats and risk of heart disease. Although
[[Page 28241]]
both soluble fiber sources affect the same CHD risk factor (i.e., blood
lipid levels), the agency cannot assume that foods containing a blend
of these grains would have the same ability to affect blood total and
LDL-cholesterol levels that a product containing either whole oats or
psyllium apparently has. Therefore, if a manufacturer can demonstrate
that a diet that is low in saturated fat and cholesterol that includes
a blend of the eligible soluble fibers listed in
Sec. 101.81(c)(2)(ii)(A) and (c)(2)(ii)(B) has an effect on the risk of
heart disease, the manufacturer should petition to amend Sec. 101.81
further. In addition, because the qualifying level that FDA is
proposing for soluble fiber from psyllium differs from that which it
adopted for -glucan soluble fiber from whole oats, the issue
of an appropriate qualifying level for a blended product should be
addressed in any petition.
In the preamble to the final rule in which it adopted Sec. 101.81,
the agency explained that the approach it used to derive the qualifying
level of 0.75 g per RACC for whole oat products is somewhat different
from the one that it used in authorizing other health claims (62 FR
3584 at 3592). The agency explained that the guiding principle for
other health claims was to use the established definition for ``good
source'' or ``high in,'' which characterize the amount of a nutrient
based on a percentage of the Daily Reference Value (DRV) for the
nutrient, in a serving of food as the qualifying level. In this way,
products that qualify to bear the claim contain a meaningful level of
the substance per serving compared to the recommended intake of the
substance from all food sources. However, there is no DRV for soluble
fiber. While the agency concluded that the approach it took to
establish the qualifying level in Sec. 101.81 was appropriate, it
stated that it intends to propose to establish a DRV for soluble fiber,
and, once that rulemaking is completed, assuming it results in a DRV,
it would revisit the requirements in Sec. 101.81 and propose any
changes in its provisions that are necessary. For the purposes of any
final rule that results from this rulemaking, the agency will also
revisit the requirements of Sec. 101.81(c)(2)(iii) if a DRV is
established for soluble fiber.
C. Soluble Fiber From Certain Foods and From Eligible Food Sources
In light of the agency's tentative decision to broaden Sec. 101.81
to include soluble fiber from psyllium, the agency is proposing to
modify the section heading of Sec. 101.81 from ``Soluble fiber from
whole oats and risk of coronary heart disease'' to ``Health claims:
soluble fiber from certain foods and risk of coronary heart disease.''
The statement ``soluble fiber from certain foods'' reflects the fact
that the subject of the claim is no longer a specific source of soluble
fiber, i.e., -glucan from whole oats, but rather a broader
class of substances that includes those sources of soluble fiber for
which there is significant scientific agreement that they may help to
reduce the risk of heart disease.
The statement ``soluble fiber from whole oats'' also appears in
several paragraphs of Sec. 101.81. The agency is proposing to revise
this statement where it appears to state ``soluble fiber from certain
foods.'' The paragraphs of Sec. 101.81 that will be affected by this
change, if it is adopted, include: (a), (a)(3), (b), (b)(2), (c)(2)(i),
(c)(2)(i)(A), (d)(3), and (e).
The agency is proposing to revise the statement ``soluble fiber
from whole oats'' in three paragraphs of Sec. 101.81, paragraphs
(c)(2)(i)(E), (c)(2)(i)(F), and (d)(2), to read ``soluble fiber from
the eligible food sources from paragraph (c)(2)(ii) of this section.''
The agency tentatively finds that the statement ``soluble fiber from
the eligible food sources * * *'' more accurately identifies the
particular sources of soluble fibers that may be the subject of the
claim. For example, Sec. 101.81(c)(2)(i)(E) now specifies that the
claim must not attribute any degree of risk reduction for coronary
heart disease to diets low in saturated fat and cholesterol that
include soluble fiber from whole oats. The eligible food sources in
this proposed rule include whole oats and psyllium, so FDA is proposing
to revise Sec. 101.81(c)(2)(i)(E) to reflect the broader coverage of
the claim.
The agency notes, however, that it is not proposing changes to the
model claims in Sec. 101.81(e) (modified at 62 FR 15342). In both
example claims, the name of the soluble fiber source from
Sec. 101.81(c)(2)(ii) (Eligible source of soluble fiber) is provided,
and, if desired, the name of the food product may be provided. For
example, Sec. 101.81(e)(1) states ``Soluble fiber from foods such as
[name of soluble fiber source from section (c)(2)(ii) of this section
and, if desired, the name of the food product], as part of a diet low
in saturated fat and cholesterol, may reduce the risk of heart
disease.'' Therefore, a claim for a psyllium-containing food may state
``Soluble fiber from foods such as psyllium, as part of a diet low in
saturated fat and cholesterol, may reduce the risk of heart disease,''
and thus no change in Sec. 101.81(e)(1) or (e)(2) is necessary to
reflect the addition of psyllium to the list of substances eligible to
bear the claim.
The agency is proposing to make some minor editorial changes in
Sec. 101.81, which have no substantive effect on this regulation.
VII. Environmental Impact
The agency has determined under 21 CFR 25.24(a)(11) that this
action is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required. This finding is based on information submitted by the
petitioner in an environmental assessment prepared using the format
described in 21 CFR 25.31a(b)(5).
VIII. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612).
Executive Order 12866 directs agencies to assess all costs and benefits
of available regulatory alternatives and, when regulation is necessary,
to select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). Executive Order 12866
classifies a rule as significant if it meets any one of a number of
specified conditions, including having an annual effect on the economy
of $100 million or adversely affecting in a material way a sector of
the economy, competition, or jobs, or if it raises novel legal or
policy issues. If a rule has a significant economic impact on a
substantial number of small entities, the Regulatory Flexibility Act
requires agencies to analyze regulatory options that would minimize the
economic impact of that rule on small entities. FDA finds that this
proposed rule is not a significant rule as defined by Executive Order
12866 and finds under the Regulatory Flexibility Act that the proposed
rule will not have a significant impact on a substantial number of
small entities.
The establishment of this health claim results in benefits and in
costs only to the extent that food manufacturers elect to take
advantage of the opportunity to use the claim. This rule will not
require that any labels be redesigned or that any product be
reformulated.
Some manufacturers are currently using FDA's approved health claim
regarding the benefits of fruits, vegetables, and grain products. This
proposed health claim will allow them to specifically highlight the
role of
[[Page 28242]]
soluble fiber from psyllium. The benefit of establishing this health
claim is to provide for new information in the market regarding the
relationship of soluble fiber from psyllium and CHD.
Costs will be incurred by small entities only if they opt to take
advantage of the marketing opportunity presented by this regulation.
FDA cannot predict the number of small entities that will choose to use
the claim. However, no firm, including small entities, will choose to
bear the cost of redesigning labels unless they believe that the claim
will result in increased sales of their product. Therefore, this rule
will not result in either a decrease in revenues or a significant
increase in costs to any small entity. Accordingly, under the
Regulatory Flexibility Act, 5 U.S.C. 605(b), the Commissioner of Food
and Drugs certifies that the proposed rule will not have a significant
economic impact on a substantial number of small entities. Therefore,
under the Regulatory Flexibility Act, no further analysis is required.
IX. Paperwork Reduction Act
FDA tentatively concludes that this proposed rule contains no
reporting, recordkeeping, labeling, or other third party disclosure
requirement. Thus, there is no ``information collection'' necessitating
clearance by the Office of Management and Budget. However, to ensure
the accuracy of this tentative conclusion, FDA is seeking comment on
whether this proposed rule to permit health claims on the association
between soluble fiber from psyllium and reduced risk of CHD imposes any
paperwork burden.
X. Effective Date
FDA is proposing to make these regulations effective upon
publication of a final rule based on this proposal.
XI. Comments
Interested persons may, on or before August 5, 1997, submit to the
Dockets Management Branch (address above) written comments regarding
this proposal. Two copies of any comments are to be submitted, except
that individuals may submit one copy. Comments are to be identified
with the docket number found in brackets in the heading of this
document. Received comments may be seen in the office above between 9
a.m. and 4 p.m., Monday through Friday.
XII. References
The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. Kellogg Co., ``Petition for Health Claim--Soluble Fiber from
Psyllium and Coronary Heart Disease,'' June 12, 1996 [CP1].
2. Scarbrough, F. Edward, Center for Food Safety and Applied
Nutrition, FDA, Letter to Richard M. Clark, Kellogg Co., September
18, 1996.
3. DHHS, PHS, ``The Surgeon General's Report on Nutrition and
Health,'' U.S. Government Printing Office, Washington, DC, pp. 83-
137, 1988.
4. Food and Nutrition Board, National Academy of Sciences,
``Diet and Health: Implications for Reducing Chronic Disease Risk,''
National Academy Press, Washington, DC, pp. 291-309 and 529-547,
1989.
5. DHHS, PHS and the National Institutes of Health, ``National
Cholesterol Education Program: Population Panel Report,'' Bethesda,
MD, pp. 1-40, 1990.
6. Sempos, C. T., J. I. Cleeman, M. D. Carroll, C. L. Johnson,
P. S. Bachorik, D. J. Gordon, V. L. Burt, R. R. Briefel, C. D.
Brown, K. Lippel, and B. M. Rifkind, ``Prevalence of High Blood
Cholesterol Among U.S. Adults. An Update Based on Guidelines From
the Second Report of the National Cholesterol Education Program
Adult Treatment Panel,'' Journal of the American Medical
Association, 269:3009-3014, 1993.
7. LSRO, FASEB, ``Physiological Effects and Health Consequences
of Dietary Fiber,'' Bethesda, MD, 1987.
8. LSRO, FASEB, ``Evaluation of Publicly Available Scientific
Evidence Regarding Certain Nutrient-Disease Relationships: 6.
Dietary Fiber and Cardiovascular Disease,'' Bethesda, MD, 1991.
9. Abraham, Z. D. and T. Mehta, ``Three-week Psyllium-husk
Supplementation: Effect on Plasma Cholesterol Concentrations, Fecal
Steroid Excretion, and Carbohydrate Absorption in Men,'' American
Journal of Clinical Nutrition, 47:67-74, 1988.
10. Anderson, J. W., N. Zettwoch, T. Feldman, J. Tietyen-Clark,
P. Oeltgen, and C. W. Bishop, ``Cholesterol-lowering Effects of
Psyllium Hydrophilic Mucilloid for Hypercholesterolemic Men,''
Archives of Internal Medicine, 148:292-296, 1988.
11. Anderson, J. W, T. L. Floore, P. B. Geil, D. Spencer, and T.
K. Balm, ``Hypercholesterolemic Effects of Different Bulk--Forming
Hydrophilic Fibers as Adjuncts to Dietary Therapy in Mild to
Moderate Hypercholesterolemia,'' Archives of Internal Medicine,
151:1597-1602, 1991.
12. Anderson, J. W., S. Riddell-Mason, N. J. Gustafson, S. F.
Smith, and M. Mackey, ``Cholesterol Lowering Effects of Psyllium-
Enriched Cereal as an Adjunct to a Prudent Diet in the Treatment of
Mild to Moderate Hypercholesterolemia,'' American Journal of
Clinical Nutrition, 56:93-98, 1992.
13. Anderson, J. W., M. H. Davidson, L. Blonde, W. V. Brown, W.
J. Howard, H. Ginsberg, L. D. Allgood, and K. W. Weingand, ``Long-
term Cholesterol-lowering Effects of Psyllium as an Adjunct to Diet
Therapy in the Treatment of Hypercholesterolemia,'' Unpublished,
1994.
14. Bell, L. P., K. Hectorne, H. Reynolds, T. K. Balm, and D. B.
Hunninghake, ``Cholesterol-lowering Effects of Psyllium Hydrophilic
Mucilloid--adjunct Therapy to a Prudent Diet for Patients with Mild
to Moderate Hypocholesterolemia,'' Journal of the American Medical
Association, 261:3419-3423, 1989.
15. Davidson, M. H., ``Long-term Influence of Psyllium-enriched
Foods on Serum Lipids among Subjects with Hypercholesterolemia
Consuming a Low Fat Diet,'' Unpublished study, 1996.
16. Everson, G. T., B. P. Daggy, C. McKinley, and J. A. Story,
``Effects of Psyllium Hydrophilic Mucilloid on LDL-synthesis and
Bile Acid Synthesis in Hypercholesterolemic Men,'' Journal of Lipid
Research, 33:1183-1192, 1992.
17. Gelissen, I. C., B. Brodie, and M. A. Eastwood, ``Effect of
Plantago Ovata (Psyllium) Husk and Seeds on Sterol Metabolism:
Studies in Normal and Ileostomy Subjects,'' American Journal of
Clinical Nutrition, 59:395-400, 1994.
18. Keane, W. F., V. T. Miller, L. P. Bell, C. E. Halstenson, L.
D. Allgood, H. Tully, J. C. LaRosa, ``Effect of Psyllium in
Conjunction with a Low-fat Diet on Plasma Lipids in Elderly Patients
with Mild-to-moderate Hypercholesterolemia,'' Unpublished, 1996.
19. Levin, E. G., V. T. Miller, R. A. Muesing, D. B. Stoy, T. K.
Balm, and J. C. LaRosa, ``Comparison of Psyllium Hydrophilic
Mucilloid and Cellulose as Adjuncts to a Prudent Diet in the
Treatment of Mild to Moderate Hypercholesterolemia,'' Archives of
Internal Medicine, 150:1822-1827, 1990.
20. Neal, G. W. and T. K. Balm, ``Synergistic Effects of
Psyllium in the Dietary Treatment of Hypercholesterolemia,''
Southern Medical Journal, 83:1131-1137, 1990.
21. Schectman, G., J. Hiatt, A. Hartz, ``Evaluation of the
Effectiveness of Lipid-lowering Therapy (Bile Acid Sequestrants,
Niacin, Psyllium, and Lovastatin) for Treating Hypercholesterolemia
in Veterans,'' American Journal of Cardiology, 71:759-765, 1993.
22. Sprecher, D. L., B. V. Harris, A. C. Goldberg, E. C.
Anderson, L. M. Bayuk, B. S. Russell, D. S. Crone, C. Quinn, J.
Bateman, B. R. Kuzmak, and L. D. Allgood, ``Efficacy of Psyllium in
Reducing Serum Cholesterol Levels in Hypercholesterolemic Patients
on High- or Low-fat Diets,'' Annals of Internal Medicine, 119:545-
554, 1993.
23. Stoy, D. B., J. C. LaRosa, B. K. Brewer, M. Mackey, R. A.
Muesing, ``Cholesterol-lowering Effects of Ready-to-eat Cereal
Containing Psyllium,'' Journal of the American Dietetic Association,
93:910-912, 1993.
24. Stoy, D. B., J. C. LaRosa, B. K. Brewer, L. G. Saldhanda, R.
A. Muesing, ``Lipid Lowering Effects of Ready-to-eat Cereal
Containing Psyllium: a Randomized Crossover Trial,'' Unpublished,
1993.
25. Summerbell, C. D., P. Manley, D. Barnes, and A. Leeds, ``The
Effects of Psyllium on Blood Lipids in Hypercholesterolemic
Subjects,'' Journal of Human Nutrition and Dietetics, 7:147-151,
1994.
26. Weingand, K. W., N-A. Le, B. R. Kuzmak, W. V. Brown, B. P.
Daggy, T. A.
[[Page 28243]]
Miettinen, B. V. Howard, and W. J. Howard, ``Effects of Psyllium on
Cholesterol and Low-density Lipoprotein Metabolism in Subjects with
Hypercholesterolemia,'' Unpublished, no date.
27. Gupta, R. R., C. G. Agrawal, G. P. Singh, and A. Ghatak,
``Lipid-lowering Efficacy of Psyllium Hydrophilic Mucilloid in Non-
insulin Dependent Diabetes Mellitus with Hyperlipidaemia,'' Indian
Journal of Medical Research, 100:237-241, 1994.
28. Stewart, R. B., W. E. Hale, M. T. Moore, F. E. May, and R.
G. Marks, ``Effect of Psyllium Hydrophilic Mucilloid on Serum
Cholesterol in the Elderly,'' Digestive Diseases and Sciences,
36:329-334, 1991.
29. Lee, S. C., E. Farmakalidis, and L. Prosky, ``Determination
of Soluble and Insoluble Dietary Fiber in Psyllium-containing Cereal
Products,'' Journal of the AOAC International, 78:724-729, 1995.
30. Jenkins, D. J. A., S. Mueller, T. M. S. Wolever, V. Rao, T.
Ransom, D. Boctor, P. Spadafor, C. Mehling, L. K. Relle, E. Chow, K.
MacMillan, and V. Fulgoni, ``High Soluble Fiber Foods Reduce Serum
Lipids Even When Diets Are Already Low in Saturated Fat and
Cholesterol,'' Unpublished study, 1992.
31. LSRO, ``The Evaluation of the Safety of Using Psyllium Seed
Husk as a Food Ingredient,'' Bethesda, MD, December 1993.
32. James, J. M., S. K. Cooke, A. Barnett, and H. A. Sampson,
``Anaphylactic Reactions to a Psyllium-containing Cereal,'' Journal
of Allergy and Clinical Immunology, 88:402-408, 1991.
33. Ross, R., ``Atherosclerosis,'' in Cecil - Textbook of
Medicine, J. B. Wyngaarden, L. H. Smith, and J. C. Bennett, editors,
Harcourt Brace Jovanevich, Inc., Philadelphia, p. 293, 1992.
34. USP, ``The National Formulary,'' US Parmacopeial Convention,
Inc., Rockville, MD, UPS 23, NF 18, p. 1341, 1995.
35. Saltsman, J., Memo to file with Table 1: ``Summary of
clinical trials: psyllium and CHD,'' and Table 2: ``Psyllium and
CHD,'' January 28, 1997.
36. Goodlad, R. A., B. Ratcliffe, C. Y. Lee, and N. A. Wright,
``Dietary Fibre and the Gastrointestinal Tract: Differing Trophic
Effects on Muscle and Mucosa of the Stomach, Small Intestine, and
Colon,'' European Journal of Clinical Nutrition, 49(Suppl. 3):S178-
S181, 1995.
37. Wasan, H. S. and R. A. Goodlad, ``Fibre-supplemented Foods
May Damage Your Health, Lancet, 348:319-320, 1996.
List of Subjects in 21 CFR Part 101
Food labeling, Incorporation by reference, Nutrition, Reporting and
recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 101 be amended as follows:
PART 101--FOOD LABELING
1. The authority citation for 21 CFR part 101 continues to read as
follows:
Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act
(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342,
343, 348, 371).
2. Section 101.81 is amended by revising the section heading, the
heading for paragraphs (a) and (b), and paragraphs (a)(3), (b)(2),
(c)(2)(i) introductory text, (c)(2)(i)(A), (c)(2)(i)(E), (c)(2)(i)(F),
(c)(2)(iii)(A), (d)(2), (d)(3), and (e), and by adding paragraph
(c)(2)(ii)(B) to read as follows:
Sec. 101.81 Health claims: Soluble fiber from certain foods and risk
of coronary heart disease (CHD).
(a) Relationship between diets that are low in saturated fat and
cholesterol and that include soluble fiber from certain foods and the
risk of CHD.
* * * * *
(3) Scientific evidence demonstrates that diets low in saturated
fat and cholesterol may reduce the risk of CHD. Other evidence
demonstrates that the addition of soluble fiber from certain foods to a
diet that is low in saturated fat and cholesterol may also help to
reduce the risk of CHD.
(b) Significance of the relationship between diets that are low in
saturated fat and cholesterol and that include soluble fiber from
certain foods and the risk of CHD.
* * * * *
(2) Intakes of saturated fat exceed recommended levels in the diets
of many people in the United States. One of the major public health
recommendations relative to CHD risk is to consume less than 10 percent
of calories from saturated fat and an average of 30 percent or less of
total calories from all fat. Recommended daily cholesterol intakes are
less than 300 mg per day. Scientific evidence demonstrates that diets
low in saturated fat and cholesterol are associated with lower blood
total and LDL-cholesterol levels. Soluble fiber from certain foods,
when included in a low saturated fat and cholesterol diet, also helps
to lower blood total and LDL-cholesterol levels.
(c) * * *
(2) * * *
(i) Nature of the claim. A health claim associating diets that are
low in saturated fat and cholesterol and that include soluble fiber
from certain foods with reduced risk of heart disease may be made on
the label or labeling of a food described in paragraph (c)(2)(iii) of
this section, provided that:
(A) The claim states that diets that are low in saturated fat and
cholesterol and that include soluble fiber from certain foods ''may``
or ''might`` reduce the risk of heart disease.
* * * * *
(E) The claim does not attribute any degree of risk reduction for
CHD to diets that are low in saturated fat and cholesterol and that
include soluble fiber from the eligible food sources from paragraph
(c)(2)(ii) of this section; and
(F) The claim does not imply that consumption of diets that are low
in saturated fat and cholesterol and that include soluble fiber from
the eligible food sources from paragraph (c)(2)(ii) of this section is
the only recognized means of achieving a reduced risk of CHD.
(ii) * * *
(B)(1) Psyllium husk from the dried seed coat (epidermis) of the
seed of Plantago (P.) ovata, known as blond psyllium or Indian
psyllium; P. indica; or P. psyllium. To qualify for this claim,
psyllium shall have a purity of no less than 95 percent, such that it
contains 3 percent or less protein, 4.5 percent or less of light
extraneous matter, and 0.5 percent or less of heavy extraneous matter,
but in no case may the combined extraneous matter exceed 4.9 percent,
as determined by U.S. Pharmacopeia (USP) methods described in USP's
''The National Formulary,`` USP 23, NF 18, p. 1341, (1995), which is
incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR
part 51. Copies may be obtained from the U.S. Pharmacopeial Convention,
Inc., 12601 Twinbrook Pkwy., Rockville, MD 20852, or may be examined at
the Center for Food Safety and Applied Nutrition's Library, 200 C St.
SW., rm. 3321, Washington, DC, or at the Office of the Federal
Register, 800 North Capitol St. NW., suite 700, Washington, DC;
(2) FDA will determine the amount of soluble fiber that is provided
by psyllium by using a modification of the Association of Official
Analytical Chemists' (AOAC's) method for soluble dietary fiber (991.43)
described by Lee et al., ''Determination of Soluble and Insoluble
Dietary Fiber in Psyllium-containing Cereal Products,`` Journal of the
AOAC International, 78(No. 3):724-729, 1995, which is incorporated by
reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies
may be obtained from the Association of Official Analytical Chemists
International, 481 North Frederick Ave., suite 500, Gaithersburg, MD
20877-2504, or may be examined at the Center for Food Safety and
Applied Nutrition's Library, 200 C St. SW., rm. 3321, Washington, DC,
or at the Office of the Federal Register, 800 North Capitol St. NW.,
suite 700, Washington, DC;
(iii) * * *
(A) The food product shall include:
(1) One or more of the whole oat foods from paragraph (c)(2)(ii)(A)
of this
[[Page 28244]]
section, and the whole oat foods shall contain at least 0.75 gram (g)
of soluble fiber per reference amount customarily consumed of the food
product; or
(2) Psyllium that complies with paragraph (c)(2)(ii)(B) of this
section, and the psyllium food shall contain at least 1.7 g of soluble
fiber per reference amount customarily consumed of the food product;
* * * * *
(d) * * *
(2) The claim may state that the relationship between intake of
diets that are low in saturated fat and cholesterol and that include
soluble fiber from the eligible food sources from paragraph (c)(2)(ii)
of this section and reduced risk of heart disease is through the
intermediate link of ''blood cholesterol`` or ''blood total- and LDL-
cholesterol;``
(3) The claim may include information from paragraphs (a) and (b)
of this section, which summarize the relationship between diets that
are low in saturated fat and cholesterol and that include soluble fiber
from certain foods and coronary heart disease and the significance of
the relationship;
* * * * *
(e) Model health claim. The following model health claims may be
used in food labeling to describe the relationship between diets that
are low in saturated fat and cholesterol and that include soluble fiber
from certain foods and reduced risk of heart disease:
(1) Soluble fiber from foods such as [name of soluble fiber source
from paragraph (c)(2)(ii) of this section and, if desired, the name of
the food product], as part of a diet low in saturated fat and
cholesterol, may reduce the risk of heart disease.
(2) Diets low in saturated fat and cholesterol that include soluble
fiber from [name of soluble fiber source from paragraph (c)(2)(ii) of
this section and, if desired, the name of the food product] may reduce
the risk of heart disease.
Dated: May 15, 1997.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 97-13379 Filed 5-21-97; 8:45 am]
BILLING CODE 4160-01-F
Note: The following table will not appear in the Code of Federal
Regulations.
Table 1.--Summary of Clinical Trials with Hypercholesterolemics: Psyllium and Coronary Heart Disease
----------------------------------------------------------------------------------------------------------------
Supplements
(Psyllium, Diet Intake Magnitude of
Study Duration Treatment Number of Placebo) of groups: Magnitude of Placebo
Subjects Soluble Fiber Sat fat % E; PSY Effect* Effect
g/d CHOL mg/d
----------------------------------------------------------------------------------------------------------------
Levin et Base: 8-wk Step 1; Tx: 16- PSY: 30 (26 10.2 g/d bulk Sat fat: PSY- CHOL: -13 mg/ CHOL: 0; LDL-
al. wk Step 1+supplement men) laxative, 6.7%; C- dL (5.6%) C -2.2%; HDL-
(Ref. 19) Pla: 28 (23 cellulose 6.3% LDL-C: -13 mg/ C:
men) PSY: CHOL: PSY- dL (8.6%)
166 mg; C- +6% (sig
7 g SF 135 mg from PSY)
Bell et Base: 12-wk Step 1; Tx: 8- PSY: 40 (20 10.2 g/d bulk Sat fat: PSY- CHOL: -9 mg/ CHOL: 0; LDL-
al. wk Step 1+supplement men) laxative, 8-10%; C- dL (4.2%) C -0.2%; HDL-
(Ref. 14) Pla: 35 (18 cellulose 7.7-8.6% LDL-C: -12 mg/ C no sig dif
men) PSY: CHOL: PSY- dL (7.7%) (grps)
168 mg; C-
7 g SF 206 mg
Davidson Base: 8-wk Step 1; Tx: 24- PSY 1 56 (31 3.4 g, 6.8 g, Sat fat: PSY- CHOL: -3% CHOL: +1.7%;
et al. wk Step 1 + PSY or men) 10.2 g/d; 7-8.6%; C- 7- (PSY 3) LDL-C: +3%
(Ref. 15) control food (3 servings/ PSY 2 40 (24 incorporated 8.6% LDL-C: -5% HDL-C: No sig
d) men) into foods: CHOL: PSY 1- (PSY 3) dif (grps)
PSY 3 43 (28 C foods: no 151 mg; PSY
men) PSY 2- 181; PSY
C 59 PSY 1: 3- 169C- 145
mg
2.3 g SF,
PSY 2:
.6 g;
PSY 3:
7 g
Everson Regular diet; 5-d Base; 2 20 men 15.3 g/d bulk Sat fat: PSY- CHOL: -14 mg/ CHOL: -1.9%;
et al. 40-d periods; 11-d laxative, 12%; C- 13.2 dL (-5%) LDL-C: -2.7%
(Ref. 16) washout; crossover cellulose % LDL-C: -15 mg/ HDL-C: No sig
PSY: CHOL: PSY- dL (8%) dif (grps)
296 mg; C-
10 g SF 274 mg
Jenkins Base: 2-mo Step 2; Tx: 2 1- 12 Ss (3m/9f) Mean intake: Sat fat: 4% CHOL: -16.6 HDL-C: No sig
et al. mo Step 2 metabolic 9.35 g/d PSY all grps mg/dL dif (grps)
(Ref. 30) diets, crossover, washout in cereal PSY: 36 mg; Tx
PSY: 6.8 g SF C: 29 mg difference:
CHOL PSY- 36 3.4%
mg; C-29 mg LDL-C: -9.3
mg/dL
Tx
difference:
5.1%
Stoy et 4-wk Step 1; Step 1 + 23 men Estimated Sat fat: PSY: CHOL: -10 mg/ HDL-C: No sig
al. (8x5x5 wks): Grp 1: PSY- 11.6 g/d PSY 5.1% (Grp 1) dL (4%) dif (grps)
(Ref. 23) Pla-PSY; Grp 2: Pla-PSY- from cereal: and 5.1% LDL-C: -11 mg/
Pla (Grp 2) dL (6%)
8 g SF; Wheat: 4.5%
Wheat (Grp 1) and
cereal: 5.0% (Grp 2)
CHOL: PSY 141-
3 g SF 165 mg
Wheat: 164 mg
(Grp 1), 117-
170 (Grp 2)
[[Page 28245]]
Stoy et 4-wk Step 1; Step 1 + 22 men Estimated Sat fat: PSY: CHOL: -10 mg/ HDL-C: No sig
al. (8x5x5 wks): Grp 1: PSY- 11.6 g/d PSY 4.8 (Grp 1) dL (4%) dif (grps)
(Ref. 24) Pla-PSY; Grp 2: Pla-PSY- from cereal: and 5.2% LDL-C: -11 mg/
Pla (Grp 2) dL (6%)
8 g SF; Wheat: 4.7%
Wheat (Grp 1) and
cereal: 5.6% (Grp 2)
CHOL: PSY 155-
3 g SF 163 mg
Wheat: 133 mg
(Grp 1), 169-
172 (Grp 2)
----------------------------------------------------------------------------------------------------------------
* Significant differences between treatment and placebo groups unless otherwise indicated.
Abbreviations Used in Table 1
C Control
CHOL Blood total cholesterol
d Day
E Energy
g Gram
grp Group
HDL-C High density lipoprotein cholesterol
LDL-C Low density lipoprotein cholesterol
m/f Number of males, number of females
mg/dL Milligrams per deciliter
mo Months
oz Ounces
Pla Placebo
Pro Protein
PSY Psyllium
Sat fat Saturated fat
SF Soluble fiber
Sig Dif Statistically significant difference
Step 1 30% kcals fat, 55% CHO, 15% Pro, <300 mg="" cholesterol="" tx="" treatment="" wk="" week=""> approximately
% Percent
[FR Doc. 97-13379 Filed 5-21- 97; 8:45 am]
BILLING CODE 4160-01-F
