[Federal Register Volume 68, Number 150 (Tuesday, August 5, 2003)]
[Rules and Regulations]
[Pages 46364-46402]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-19508]



[[Page 46363]]

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Part III





Department of Health and Human Services





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Food and Drug Administration



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21 CFR Part 172



Food Additives Permitted for Direct Addition to Food for Human 
Consumption; Olestra; Final Rules

  Federal Register / Vol. 68, No. 150 / Tuesday, August 5, 2003 / Rules 
and Regulations  

[[Page 46364]]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 172

[Docket No. 2000F-0792]


Food Additives Permitted for Direct Addition to Food for Human 
Consumption; Olestra

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the food 
additive regulations to remove the requirement for the label statement 
prescribed specifically for savory snack products that contain olestra. 
This action is in response to a petition filed by the Procter and 
Gamble Co.

DATES: The regulation is effective August 5, 2003. Submit written 
objections and requests for a hearing by September 4, 2003.

ADDRESSES: Submit written objections to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, rm. 1061, 5630 
Fishers Lane, Rockville, MD 20852. Submit electronic objections to 
http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Mary D. Ditto, Center for Food Safety 
and Applied Nutrition (HFS-255), Food and Drug Administration, 5100 
Paint Branch Pkwy., College Park, MD 20740-3835, 202-418-3102.

SUPPLEMENTARY INFORMATION: 

Table of Contents

I. Subject of Petition
II. Background
    A. Basis for Requiring the Label Statement--1996 Decision
    1. Legal Authority for the 1996 Label Statement
    2. GI Issues Associated With Olestra
    3. Nutritional Issues Associated With Olestra
    B. Opportunity for Comment and Consideration of New Data
    1. Request for Comments on Label Statement Required by the 1996 
Final Rule
    2. P&G's Commitment To Further Studies
    3. FDA's Commitment to Convene an FAC Meeting
    4. P&G's Petition To Remove the Requirement for the Label 
Statement
    5. Comments Received
III. Data and Information Since the 1996 Final Rule
    A. Introduction
    B. Surveys and Postmarket Passive Surveillance Regarding GI 
Effects
    1. Telephone Surveys Regarding GI Complaints
    a. P&G
    b. CSPI
    2. Postmarket Passive Surveillance by P&G
    3. Postmarket Surveillance Reports From CSPI
    4. Comments Regarding Consumer Reports
    C. Studies Regarding GI Effects
    1. Rechallenge Study
    2. Acute Consumption Study
    3. Home Consumption Study
    4. Stool Composition Study
    5. Comments Regarding the GI Studies
    D. A Study Regarding Nutritional Effects--Active Surveillance
    1. Active Surveillance Study by P&G
    2. Comments Regarding the Active Surveillance Study
    E. Consultations and Literature Review Regarding Nutritional 
Effects
    F. Consumer Perception Studies of the Label Statement
    1. 1996 Consumer Studies
    2. 1999 Consumer Studies
    G. 1998 FAC Discussion of the Label Statement
IV. FDA's Conclusions
    A. The Applicable Legal Standard
    B. FDA's Conclusions Regarding Gastrointestinal Effects
    1. Basis of the 1996 Final Rule--GI Effects
    a. Abdominal cramping
    b. Loose stools
    2. Data in the Current Petition--GI Effects
    a. Abdominal cramping
    b. Loose stools
    C. FDA's Conclusions Regarding Nutritional Effects
    1. Basis of the 1996 Final Rule--Nutritional Effects
    2. Data in the Current Petition--Nutritional Effects
V. Response to Comments on the Label
    A. Label Statement for GI Effects
    B. Label Statement for Nutritional Effects
    C. Labeling for Special Populations
    D. Label Statement in Its Entirety
    E. Data and Information Considered in this Rulemaking
    F. Safety of Olestra
    G. Allergenicity of Olestra or Olestra-Containing Foods
    H. Nutrition Labeling and Claims
    I. Appearance of the Label Statement
    J. Labeling for Single-Serving Packages
    K. 1995 and 1998 FAC Meetings
VI. Summary
VII. Environmental Impact
VIII. Inspection of Documents
IX. Objections
X. References

I. Subject of Petition

    In a notice in the Federal Register of March 3, 2000 (65 FR 11585-
11586), FDA announced that a food additive petition had been filed by 
the Procter & Gamble Co., 6071 Center Hill Ave., Cincinnati, OH 45224 
(P&G, the petitioner) proposing that the food additive regulations be 
amended in Sec.  172.867 Olestra (21 CFR 172.867) to remove the 
requirement for the label statement prescribed in Sec.  172.867(e).

II. Background

    In the Federal Register of January 30, 1996 (61 FR 3118, ``the 1996 
final rule'') FDA announced the approval of olestra for use as a fat 
substitute in prepackaged ready-to-eat savory snacks. Olestra is the 
common name for a mixture of substances formed by chemical combination 
of sucrose with six, seven, or eight fatty acids. The fatty acids, 
bound to sucrose by ester bonds, are derived from edible fats and oils.
    Olestra is essentially not absorbed or metabolized and passes 
unchanged through the gastrointestinal (GI) system (61 FR 3118 at 3125-
3127). Therefore, olestra has the potential to affect GI physiology and 
function. Additionally, because of olestra's physical properties, fat-
soluble nutrients present in olestra-containing foods \1\ or other 
foods in the GI tract at the same time as olestra can partition into 
olestra and pass through the GI tract without being absorbed by the 
body. Therefore, FDA required the addition of fat-soluble vitamins A, 
D, E, and K, to savory snacks containing olestra to compensate for any 
inhibition of absorption by olestra (Sec.  172.867(d)).
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    \1\ Olestra has only been approved for use as a fat substitute 
in savory snacks. Throughout this document, we refer to olestra-
containing foods to include those savory snacks made with olestra as 
well as other olestra-containing foods used in the preapproval 
studies for olestra.
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    At the time of the 1996 final rule, FDA concluded that, to avoid 
being misbranded within the meaning of sections 201(n) and 403(a)(1) of 
the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321(n) 
and 343(a)(1)), olestra-containing foods would need to bear a label 
statement to inform consumers about possible effects of olestra on the 
GI system. The label statement also would clarify that the added 
vitamins were present to compensate for any nutritional effects of 
olestra, rather than to provide enhanced nutritional value. Therefore, 
the 1996 final rule required that foods containing olestra be labeled 
with the following statement in a boxed format: ``THIS PRODUCT CONTAINS 
OLESTRA. Olestra may cause abdominal cramping and loose stools. Olestra 
inhibits the absorption of some vitamins and other nutrients. Vitamins 
A, D, E, and K have been added.'' (Sec.  172.867(e)(1)). FDA included 
the term ``other nutrients'' because any nutrient that is as lipophilic 
as these vitamins would also be affected, although there was no known 
basis for adding such nutrients back. The agency also required that the 
statement be made in a standardized format that specifies, among other 
things, type style and type size, and that

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the label statement be surrounded by a box to ensure proper prominence. 
This requirement was established under section 409(c)(3)(B) of the act 
(21 U.S.C. 348(c)(3)(B)), which prohibits approval of a food additive 
if the proposed use would result in misbranding of food (61 FR 3118 at 
3160). The legal authority and scientific basis that underlaid the 
requirement for this label statement are reviewed in detail in the next 
section of this document.

A. Basis for Requiring the Label Statement--1996 Decision

1. Legal Authority for the 1996 Label Statement
    Under section 403(a)(1) of the act, a food is deemed to be 
misbranded if its labeling is false or misleading in any particular. 
Section 201(n) of the act amplifies what is meant by ``misleading.'' 
Section 201(n) of the act states that in determining whether labeling 
is misleading, the agency shall take into account not only 
representations made or suggested about the product, but also the 
extent to which the labeling fails to reveal facts material in light of 
such representations or material with respect to consequences which may 
result from use under the conditions of use prescribed in the labeling 
or under such conditions of use as are customary or usual (see 21 CFR 
1.21). Thus, the omission of such material fact from the label or 
labeling of a food causes the product to be misbranded within the 
meaning of sections 201(n) and 403(a)(1) of the act.
2. GI Issues Associated With Olestra
    As noted, olestra is not digested or absorbed, and it passes 
through the GI tract intact. The petitioner conducted a number of 
studies to address issues of potential concern with respect to the 
effect of olestra as it passes through the GI tract (61 FR 3118 at 
3152-3159). For example, during studies designed primarily to assess 
potential effects of olestra on absorption of fat-soluble dietary 
components present in the gut at the same time, the petitioner also 
assessed the potential for olestra to elicit GI symptoms such as 
cramping, bloating, loose stools, and diarrhea-like symptoms by 
collecting reports from participants in the studies. In two human 
nutritional studies \2\ (88 and 100 subjects respectively), the entire 
diet of the subjects was controlled during the length of an 8-week 
study period. The studies were parallel, double-blind, and placebo-
controlled, with olestra dosages of 0 (placebo), 8, 20, and 32 grams 
per day (g/d).\3\ The diets were formulated so that the total 
digestible fat (triglyceride) content was the same for all treatment 
groups. Triglyceride was added into the diets in the form of butter, 
margarine, or vegetable oil to compensate for the amount of fat 
replaced by olestra in the olestra-containing foods. Olestra was added 
to various food items by substituting olestra for triglyceride in 
recipes or in cooking oils. Therefore, the total amount of lipid-like 
material (digestible triglyceride plus olestra) increased with 
increasing olestra dose. Each meal contained olestra or the 
corresponding placebo (triglyceride). Subjects were questioned daily 
about changes in their health, including GI symptoms. To facilitate 
collection of GI symptom data, a questionnaire provided a list of 
common GI symptoms along with general definitions of each and was 
completed by each subject to capture data about the type, severity, and 
duration of symptoms experienced. As noted in the 1996 final rule (61 
FR 3118 at 3152), the petitioner stated that the two 8-week studies 
were not intended to examine GI symptoms under real-life consumption 
conditions where snacks are not consumed every day with every meal and 
where people may moderate intake if they experience GI symptoms.
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    \2\ In evaluating olestra's nutritional effects, the petitioner 
conducted two 8-week clinical studies, the 8-week clinical dose 
response study (8-week DR), and the 8-week clinical vitamin 
restoration study (8-week VR)(61 FR 3118 at 3133-3134). In this 
document, when discussing the combined results of these studies, 
they will be called the two 8-week studies.
    \3\ By comparison, FDA concluded that the estimated lifetime-
averaged daily intake at the 90th percentile of olestra consumption 
would be 7.0 grams per person per day (g/p/d) (61 FR 3118 at 3124).
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    FDA's analysis of the data from the two 8-week studies (61 FR 3118 
at 3152-3154) showed that there was a dose-response effect for olestra 
with respect to two endpoints, reported diarrhea/loose stools and fecal 
urgency. Reporting of diarrhea was based on subjects' perception of 
diarrhea. FDA found no evidence that study subjects experiencing 
olestra-related symptoms described as ``diarrhea'' also experienced 
significant fluid or significant electrolyte loss. The effect of 
olestra on stool consistency is similar to that produced by liquid 
petrolatum, which softens fecal contents. FDA recognized that the 
effect observed was not diarrhea in the clinical sense, but used that 
term in the 1996 final rule, and is using that term here, because it is 
the term used in the study report. FDA also found that these GI 
symptoms cease soon after olestra is no longer consumed.
    The petitioner also conducted a study, the Fecal Parameters Study, 
designed to examine fecal composition of stools from subjects who 
reported diarrhea when consuming olestra (61 FR 3118 at 3155). The 
study consisted of two phases, a screening phase and a study phase. The 
screening phase was conducted to identify subjects who reported GI 
symptoms from olestra consumption. During the study phase, the 
identified subjects ate different amounts of olestra, and GI symptoms 
were recorded and fecal measurements were made. From the initial 
screening phase, eighteen subjects reported an increase in the 
frequency, severity, or duration of GI symptoms during the olestra 
period, relative to the placebo period. These 18 subjects were selected 
to take part in the study phase, and 15 completed the study. The study 
phase was a crossover, placebo-controlled, single-blind (subject) 
design with three treatment groups, 0, 10, and 20 g/d olestra. Each 
subject received each treatment for 7 days. The treatment periods were 
separated by 7-day washout periods. Subjects ate all treatment meals 
under supervision at the clinical site, and ate their habitual diets at 
home during the washout periods. Study subjects recorded GI symptoms 
daily. Total fecal collections were made the last 3 days of each 
treatment period. Daily stool collections were measured for wet weight, 
volume, and density, and the pooled three day samples were analyzed for 
water concentration, dry weight, olestra content, sodium (Na), 
potassium (K), chloride (Cl), total and individual bile salts, free 
fatty acids, triglycerides, and total lipids.
    Measurements of the concentration of stool water and electrolytes 
(Na, K, and Cl) suggested that these parameters did not differ in the 
stools of persons reporting ``diarrhea'' during the olestra 20 g/d 
period from those in the nondiarrheal stools (during the placebo 
period) of the same persons. However, it was not possible to analyze 
stool electrolyte values by individual stools or by individual days 
because the stools were pooled from the 3-day collection period, as is 
normally done when measuring fecal parameters. FDA noted that there 
appeared to be an increased weight of stools in those subjects 
reporting ``diarrhea'' when eating 20 g/d olestra that is not 
completely accounted for by the presence of olestra in the stools. FDA 
concluded that the results of this study indicated that there is no 
difference in stool composition (e.g., water and electrolyte content) 
when subjects consumed olestra versus placebo (61 FR 3118 at 3155).
    FDA found that the number of subjects in the Fecal Parameters Study

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who reported diarrhea increased with increasing dose of olestra (i.e., 
3 subjects (20 percent) in the placebo, 6 subjects (40 percent) who 
consumed 10 g of olestra, and 11 subjects (69 percent) who consumed 20 
g of olestra). In addition, both the mean number of reported diarrheal 
bowel movements per subject reporting any diarrhea, and the severity of 
the reported diarrhea, increased with increasing olestra consumption. 
Although there was an increase in the number of subjects reporting 
loose stools with increasing olestra dose, this increase was not 
statistically significant. FDA concluded that these results were 
qualitatively similar to the results of the 8-week studies.
    The agency concluded, based upon its evaluation of the data and 
information available at the time, that consumption of olestra causes 
GI effects such as loose stools, abdominal cramping, and diarrhea-like 
symptoms. Additionally, the agency concluded that while olestra caused 
these GI symptoms, there was no evidence that these effects represented 
adverse health consequences.
    At the time of approval, the agency did not have information about 
the potential GI effects from usual or customary consumption of olestra 
in savory snacks. Nonetheless, FDA considered it prudent to rely on the 
available data in deciding whether a label statement about olestra's 
potential effects on the GI tract was necessary. Olestra had the 
potential to be consumed in relatively large quantities by every 
segment of the U.S. population. Additionally, because olestra had never 
before been available in the marketplace, consumers had no experience 
with it and were not familiar with it or its potential to cause GI 
effects. The agency believed that providing consumers label information 
about olestra's GI effects would preclude unnecessary concerns about 
the origin of GI effects, were they to be observed, and might also 
prevent unnecessary or inappropriate medical treatment of those 
symptoms (61 FR 3118 at 3161). Based on the weight of the evidence 
about olestra's potential to cause GI effects, as well as the agency's 
belief that consumers lacked familiarity with olestra and its potential 
to cause such effects, FDA concluded at the time of olestra's approval 
that the relationship between GI symptoms and consumption of foods 
containing olestra is a fact that is material in light of the 
consequences of consuming olestra, and therefore a label statement was 
required.
3. Nutritional Issues Associated With Olestra
    FDA concluded that olestra inhibits the absorption of the fat-
soluble components of the diet when these components are present in the 
GI tract simultaneously with olestra (61 FR 3118 at 3132-3147). Such 
components include the fat-soluble vitamins A, D, E, and K, and the 
lipophilic carotenoids. Based on the data from the nutritional studies, 
FDA concluded that addition of the four fat-soluble vitamins (A, D, E, 
K) to foods containing olestra would compensate for any decreased 
absorption due to the action of olestra, thus ensuring that consumption 
of an olestra-containing food would not alter the amount of vitamin 
available for absorption (61 FR 3118 at 3144-3147). The amounts of the 
vitamins to be provided are prescribed to ensure safe use (Sec.  
172.867(d)). As required under section 403(i) of the act, these 
vitamins are declared in the ingredient listing.
    The added vitamins were not to be considered in determining 
nutrient content of the food for the nutritional label or for any 
nutrient claims, expressed or implied. This is because the added 
vitamins simply compensate for the transient impaired absorption of 
vitamins A, D, E, and K, i.e., they are added to ensure no change 
(neither increase nor decrease) in vitamin availability. Thus, the 
vitamins added to olestra do not contribute significant amounts of 
these nutrients to the diet (61 FR 3118 at 3161).
    Labeling may be considered misleading not only if it fails to 
reveal facts that are material in light of consequences that may result 
from use of a food, but also if the labeling fails to reveal facts that 
are material in light of representations made. Therefore, to set the 
context for why vitamins A, D, E, and K were added, FDA required a 
label statement providing information both that vitamins A, D, E, and K 
had been added and that olestra inhibits the absorption of vitamins. 
Because FDA believed that consumers who see vitamins A, D, E, and K in 
the ingredient listing might incorrectly believe that the food was 
fortified with these vitamins, the agency required an explanatory 
statement on the label of olestra-containing foods to inform consumers 
that olestra-containing foods were not an enhanced source of vitamins 
A, D, E, and K. The statement indicated that olestra inhibits the 
absorption of vitamins and other nutrients to explain why they were 
added. FDA included the term ``other nutrients'' because any nutrient 
that is as lipophilic as these vitamins would also be affected, 
although FDA concluded that there was no basis for adding back 
nutrients other than vitamins A, D, E, and K. In this way, FDA sought 
to make clear to consumers the reason for the presence of vitamins A, 
D, E, and K in the ingredient listing.
    Carotenoids are fat-soluble components in the diet, the majority of 
which are derived from fruits and vegetables. Data from the 
petitioner's two 8-week studies demonstrated that consumption of 
olestra inhibits absorption of carotenoids as measured by a decrease in 
serum carotenoid levels (61 FR 3118 at 3147-3149). Co-consumption of 
olestra and a carotenoid-containing food allows the greatest 
interaction between olestra and the carotenoid, thereby maximizing the 
potential for interfering with absorption of the carotenoid from the GI 
tract.
    Beta-carotene is a provitamin A carotenoid that is a dietary source 
of vitamin A; provitamin A carotenoids are converted in the body into 
vitamin A. At the time of the 1996 final rule, FDA concluded that 
supplementing olestra-containing foods with vitamin A would compensate 
for olestra's effects on the provitamin A function of carotenoids.
    In evaluating whether there is a scientific basis to require the 
addition of any carotenoids to olestra-containing foods, FDA consulted 
with scientists at the National Cancer Institute of the National 
Institutes of Health (NIH) and the National Eye Institute (NEI) of the 
NIH (61 FR 3118 at 3148-3149), and the agency's Food Advisory Committee 
(FAC) (61 FR 3118 at 3121). At the 1995 FAC meeting on olestra, experts 
with a range of views discussed whether carotenoids themselves have 
beneficial health effects, or whether it is some other substance in 
fruits and vegetables that provides the claimed health effects, in 
which case the carotenoids are serving solely as markers for fruit and 
vegetable consumption. Five different conferences or reviewing groups 
preceding the 1995 FAC meeting had examined the relationship between 
carotenoids and disease. All of these groups had concluded that there 
was insufficient evidence to recommend consumption of carotenoids, 
except to encourage the consumption of fruits and vegetables (61 FR 
3118 at 3148). Although epidemiological studies showed an association 
between diets rich in fruits and vegetables (including those that 
contain carotenoids) and decreased cancer risk, there was no direct 
evidence that carotenoids themselves were responsible for or 
contributed in a significant way to that protective benefit. Therefore, 
at the time of the approval of olestra, the agency

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concluded that the available data did not establish any identifiable 
nutritional or prophylactic benefits for carotenoids, either 
individually or collectively, aside from the provitamin A function (61 
FR 3118 at 3147-3149).
    Thus, FDA found no scientific basis for requiring the addition of 
any carotenoid to olestra-containing foods. The agency also found that 
the actual magnitude of olestra's effects on carotenoid absorption was 
likely to be within the range of the normal variation of such 
absorption due to diet and bioavailability, providing additional 
assurance that the effect of olestra on the absorption of carotenoids 
did not raise concern. Accordingly, FDA concluded that there was no 
basis for requiring a statement about carotenoids on the label of 
olestra-containing food.

B. Opportunity for Comment and Consideration of New Data

1. Request for Comments on the Label Statement Required by the 1996 
Final Rule
    Because section 409 of the act prohibits, among other things, 
approval of a food additive if doing so would cause misbranding, the 
agency concluded that the olestra label statement should be imposed as 
a requirement as part of the food additive petition process (Sec.  
172.867(e)). The agency acknowledged, however, that the specific 
wording had not been tested or subject to an opportunity for comment. 
Thus, the agency requested comments on the label statement from 
interested persons on such issues as the need for labeling, the 
adequacy of its content, and the agency's current word choices (61 FR 
3118 at 3160).
    After the publication of the 1996 final rule, the agency received 
timely comments on the label statement,\4\ as well as objections to the 
1996 final rule.\5\
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    \4\ The comments received by April 1, 1996, included the results 
of P&G's consumer focus group studies on the label statement. Frito-
Lay also submitted consumer perception studies on the olestra label 
statement. These studies are discussed in section III.F.1 of this 
document. The agency continued to receive comments on the label 
statement after April 1, 1996. In this document, FDA addresses 
comments received on the label statement regardless of whether the 
comments were received by April 1, 1996.
    \5\ Timely objections were to be filed by February 29, 1996. 
FDA's response to these objections and requests for hearing is 
published elsewhere in this issue of the Federal Register.
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2. P&G's Commitment To Further Studies
    In a letter to the agency dated January 24, 1996, the petitioner 
stated its intention to conduct focus group testing of the required 
olestra label statement, to establish a postmarket surveillance system, 
to conduct additional studies of olestra exposure (both amounts 
consumed and patterns of consumption), and to conduct additional 
studies regarding the effects of olestra consumption (61 FR 3118 at 
3160 and 3168). FDA responded that P&G was to conduct the studies it 
had identified in its letter to FDA, consistent with the timetables 
identified in that letter (61 FR 3118 at 3168).
    P&G did carry out the surveillance and studies outlined in its 
letter of commitment, and performed additional studies not mentioned in 
the January 1996 letter. After the publication of the 1996 final rule, 
P&G carried out its commitment to establish a system of passive 
surveillance to collect spontaneous reports of possible effects that 
consumers associated with the consumption of olestra-containing snacks. 
This system included establishing an outside panel of medical experts 
to review reports, followup on reports of serious illness, and provide 
FDA information about reports received.
    P&G also carried out its commitment to conduct studies on the 
exposure and effects of olestra. The active surveillance program that 
P&G sponsored was designed to examine the impact of olestra consumption 
on endpoints such as serum concentrations of carotenoids and vitamins, 
olestra consumption patterns (including frequency and amounts), and GI 
symptoms.
    These data and information were presented to the FAC in June 1998, 
and were eventually incorporated into the petition that is the subject 
of this rulemaking.
3. FDA's Commitment To Convene an FAC Meeting
    In the 1996 final rule, FDA committed to review and evaluate any 
new data and information bearing on the safety of olestra and to 
present such information to the agency's FAC within 30 months of the 
approval of the use of olestra in savory snacks (61 FR 3118 at 3168-
3169; Sec.  172.867(f)).
    FDA convened a meeting of its FAC within 30 months of the approval 
of the use of olestra in savory snacks. At an open public meeting, held 
June 15-17, 1998, new data and information concerning olestra, obtained 
since the 1996 approval were presented (Ref. 1). These new data, which 
comprise the majority of material that P&G subsequently submitted in 
its petition, are discussed in section III of this document. FDA, P&G, 
the Center for Science in the Public Interest (CSPI), and other 
interested members of the public made presentations to the Committee. 
After presentation of the new data, the FAC discussed the label 
statement specified in Sec.  172.867(e). The complete set of 
transcripts of the June 1998 FAC meeting (``the transcript'' or 
``transcript'') is publicly available through FDA's Division of Dockets 
Management and through FDA's Internet site.\6\
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    \6\ The Internet site is located at http://www.fda.gov/ohrms/dockets/ac/cfsan98t.htm#Food Advisory Committee (choose June 15, 16, 
and 17).
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4. P&G's Petition To Remove the Requirement for the Label Statement
    P&G submitted a food additive petition, dated December 1, 1999, to 
amend the food additive regulations in Sec.  172.867 Olestra by 
removing the requirement for the label statement prescribed in Sec.  
172.867(e). This petition incorporated the studies and information that 
were performed after the publication of the 1996 final rule. As noted, 
much of that material was discussed by the FAC in 1998.
5. Comments Received
    FDA received approximately 80 letters, each containing one or more 
comments, on the olestra label statement.\7\ \8\ Some of the comments 
were submitted in response to FDA's request in the 1996 final rule for 
comments on the olestra label statement. Other comments were submitted 
in response to the January 24, 1996, announcement of the approval of 
olestra for use in savory snacks. Because all of these comments 
addressed P&G's original petition, which was granted in 1996, in this 
document FDA refers to these comments as comments ``to the 1996 final 
rule.'' Comments were also submitted in response to publication in the 
Federal Register of the filing notice for the current petition (65 FR 
11585, March 3, 2000); in this document, FDA refers to these comments 
as comments ``to the current petition.''
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    \7\ FDA notes that one of the objections submitted by CSPI 
concerns the label statement required by the 1996 final rule.
    \8\ Although not part of the petition being considered in the 
current rulemaking, FDA reviewed comments regarding labeling that 
were addressed to the 1998 FAC. These comments raised no substantive 
issue that was not already considered as part of the current food 
additive petition.
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    Comments were submitted by P&G, Frito-Lay, Inc. (Frito-Lay), and 
other members of the food industry, as well as from individual 
consumers, consumer organizations, academia, trade associations, and a 
member of Congress. Several comments were filed by CSPI. Several 
parties, including Frito-Lay and

[[Page 46368]]

CSPI, submitted comments to both the 1996 final rule and the current 
petition.
    Although section 409 of the act establishes no comment period for 
food additive petitions, and the agency generally does not solicit 
comments in notices announcing the filing of a food additive petition, 
it is FDA's practice to consider any relevant comments submitted prior 
to the agency's decision on a petition.\9\ In this document, FDA 
separately discusses data from telephone surveys and passive 
surveillance regarding GI effects, new studies regarding GI effects, 
and active surveillance and other information regarding nutritional 
effects of olestra. As part of its discussion of these areas, FDA 
describes and responds to comments relevant to the topic. FDA discusses 
and responds to comments on other topics (such as the wording of the 
label statement, the prominence and placement of the label statement, 
and the need for a label statement) in a separate section (see section 
V of this document). In responding to the submitted comments, FDA has 
considered all of the data and information available in the record that 
bear on the olestra label statement, including the data and information 
in the 1996 final rule as well as the new information in the current 
petition.
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    \9\ See discussion of comments in the filing notice for this 
petition (65 FR 11585-11586, March 3, 2000).
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III. Data and Information Since the 1996 Final Rule

A. Introduction

    Olestra-containing snacks were introduced into test markets in 
April 1996, and national marketing began in February 1998. P&G 
established a system of passive surveillance to collect reports of 
possible effects that consumers associated with eating olestra-
containing snacks. This surveillance system was in place when test 
marketing began. P&G has submitted reports to the agency, as well as 
analyses of such reports. P&G also established its program for active 
surveillance to monitor, among other things, possible nutritional 
impacts of olestra consumption.
    P&G conducted studies concerning possible GI effects from consuming 
olestra-containing snacks in ``real-life'' situations. Specifically, 
P&G conducted four controlled studies concerning possible GI effects in 
humans and submitted reports about those studies to FDA.\10\ The four 
controlled studies are described as follows:
---------------------------------------------------------------------------

    \10\ A copy of the petition submitted by P&G, as well as copies 
of the studies, surveys, and other supporting materials listed here, 
can be found at the Division of Dockets Management, Docket No. 00F-
0792.
---------------------------------------------------------------------------

    [sbull] An Acute Consumption Study,
    [sbull] A Six-Week Consumption Facilitated Ad Lib Study (also 
called the Home Consumption Study),
    [sbull] A Rechallenge Study, and
    [sbull] A Stool Composition Study.
    In the current petition, P&G also submitted the following data and 
information:
    [sbull] Reports and analyses of data collected through consumer 
focus group and perception studies,
    [sbull] Surveys regarding GI symptoms,
    [sbull] Updated literature reviews on carotenoids and disease, and
    [sbull] A report and analysis of the first year of data collected 
in an Active Surveillance Study.
    CSPI also submitted reports from individuals who attributed an 
effect to the consumption of an olestra-containing food (Docket No. 
87F-0179). In some cases, CSPI obtained medical records from consumers 
and forwarded them to FDA for analysis.
    Below, FDA describes in detail the studies and information 
submitted in support of this petition, comments to the 1996 final rule 
that discuss the labeling of olestra-containing foods, comments to the 
current petition, and other relevant information.

B. Surveys and Postmarket Passive Surveillance Regarding GI Effects

1. Telephone Surveys Regarding GI Complaints
    a. P&G. P&G sponsored two telephone surveys to investigate the 
frequency and severity of GI complaints, to investigate the frequency 
of consumption of foods that consumers believe cause GI symptoms, and 
to determine knowledge about reported GI symptoms from olestra-
containing foods. Both of these surveys were performed before olestra-
containing foods were available for sale in those markets. The first 
survey was done in February 1997 in Indiana (in Marion County, where 
Indianapolis is located), which was later a test-market for olestra-
containing foods. This survey also served as a pilot study for the 
second survey, which was a national survey of the U.S. population 
completed in September 1997. National marketing of olestra-containing 
foods began in February 1998.
    The petitioner acknowledged limitations in the design of the first 
survey completed in Indiana. For example, because the first survey was 
also the pilot study, the study instrument had not yet been 
validated.\11\ Also, the sample size was small and not shown to be 
representative of the general population surveyed. Despite these 
limitations, the petitioner concluded from the survey that GI symptoms 
were very common among the adult respondents polled. Asked about the 
previous three month period, respondents reported most frequently the 
GI symptoms of gas (34.6 percent), diarrhea (33.2 percent), and 
abdominal cramps (25.8 percent). Of those respondents who experienced 
one or more GI symptoms, 14 percent reported seeking medical attention 
because of the symptom. More than half of those who experienced a GI 
symptom said it was of moderate to severe intensity. The other result 
noted by the petitioner in this study was that there are a number of 
common foods (e.g., beans, onions, spicy foods) that respondents said 
caused them to have GI symptoms, but more than 80 percent of these 
respondents said they continued to eat these foods. Approximately half 
of the respondents had heard of olestra and among that group, 18 to 28 
percent associated olestra with a GI symptom such as abdominal cramping 
or diarrhea.
---------------------------------------------------------------------------

    \11\ Data obtained from the first survey was used to validate 
the study instrument for use in the second survey.
---------------------------------------------------------------------------

    The second survey was a larger, national survey that was designed 
with a reliability check, and a portion of the survey was designed to 
be a truly random sample of respondents. In this survey, 40.5 percent 
of respondents reported having one or more GI symptoms in the previous 
month. Of those respondents reporting a GI symptom, 21.8 percent had 
abdominal pain or discomfort, and 26.9 percent reported diarrhea or 
loose stools. More than 65 percent of respondents rated each of their 
symptoms as moderate to severe in intensity, and 14 percent consulted 
physicians about their symptoms. When asked about specific foods, 
respondents reported having GI symptoms after eating foods such as 
beans (22 percent) or spicy foods (34.4 percent). Despite symptoms, 
approximately 80 percent continued to consume these foods. The 
petitioner also found that women were more likely than men to report GI 
symptoms, and that abdominal pain, discomfort, and bloating were more 
commonly reported by women. There was little difference between males 
and females for reports of diarrhea. More than half the respondents in 
this study had heard of olestra, and of those, a varying number 
associated olestra with different GI

[[Page 46369]]

symptoms (diarrhea (33 percent), loose stools (4 percent), cramps (11 
percent), other GI problems (23 percent)).
    FDA notes that in both these surveys, the percent of individuals 
reporting a GI symptom was high. FDA also notes that while the great 
majority of respondents in both surveys indicated that they consumed 
foods that caused them GI symptoms, the survey did not obtain 
information about the severity of these symptoms (Ref. 2).
    b. CSPI. In 1996, CSPI commissioned a telephone survey in cities 
where olestra-containing foods were test marketed (Cedar Rapids, IA, 
Eau Claire, WI, and Grand Junction, CO), and submitted a report of the 
results to FDA.\12\ The purpose of CSPI's survey was to determine how 
many people in the test market had tried olestra-containing snacks, and 
of those who had eaten olestra-containing snacks, how many had 
experienced GI symptoms. A random digit dialing sampling system was 
used, until a total of 506 telephone interviews were conducted in June 
and July 1996. CSPI said that 27 percent of individuals surveyed had 
tried the newly marketed olestra-containing chips, and of those, 20 
percent reported experiencing GI symptoms characterized by CSPI as an 
adverse GI effect. Respondents characterized these events as mild (58 
percent), moderate (23 percent), or severe (9 percent). CSPI also found 
that the majority of respondents (78 percent) had seen negative reports 
in the press about olestra, although only 28 percent said they were 
concerned about these possible effects. Based on this telephone survey, 
CSPI predicted that a large number of adverse events would be caused by 
the national marketing of olestra-containing foods. CSPI performed a 
separate survey of the original respondents who had not eaten olestra-
containing chips but ate other chips to assess the frequency of GI 
events associated with consumption of conventional savory snacks and 
found that only 0.5 percent associated an adverse GI effect with eating 
a triglyceride savory snack.
---------------------------------------------------------------------------

    \12\ CSPI submitted this report to Docket No. 87F-0179.
---------------------------------------------------------------------------

    CSPI commissioned a second survey, which was conducted in April and 
May 1997 in the Indianapolis area where olestra-containing foods were 
test-marketed. The purpose of the survey was to ascertain the 
consumption of olestra-containing foods and possible rate of adverse 
effects. CSPI submitted a report of the results to FDA.\13\ CSPI 
reported that the majority of respondents said they had eaten savory 
snacks in the past 8 weeks (68.8 percent), and that a smaller portion 
of respondents (32.7 percent) said they had eaten olestra-containing 
foods. CSPI said that when respondents were asked whether they had 
eaten a specific brand of chips that contain olestra, they said yes, 
but when asked whether they had eaten olestra, these consumers 
responded that they had not eaten olestra. Of the group of respondents 
who had eaten an olestra-containing food, 8.3 percent reported 
experiencing what was characterized as an adverse effect after eating 
the olestra-containing food.
---------------------------------------------------------------------------

    \13\ CSPI submitted this report to the Docket No. 87F-0179.
---------------------------------------------------------------------------

    In its review of the data and information submitted by CSPI, FDA 
found that the studies provided information about the prevalence of use 
of olestra-containing foods, awareness of GI symptoms associated with 
olestra, and sources of information that consumers were using to learn 
about GI symptoms associated with olestra. FDA disagreed, however, that 
these studies could provide information about the cause of these GI 
symptoms. FDA found that the study design was inadequate to determine 
the cause of GI symptoms. Additionally, it is known from food-borne 
illness outbreaks that attribution biases can influence consumers and 
lead to the erroneous attribution of symptoms to a particular food. 
CSPI's survey does not allow for the evaluation of erroneous 
attribution of GI symptoms to consumption of olestra-containing chips, 
i.e., other plausible causes for illness reports were not considered 
(Ref. 3).
2. Postmarket Passive Surveillance by P&G
    P&G established a system of passive surveillance to collect 
consumer reports associated with the consumption of olestra-containing 
foods. Passive surveillance refers to the collecting of spontaneous, 
voluntary reports about a product. In its petition, P&G presents an 
overview of both the utility and limitations of data obtained from 
spontaneous, postmarket consumer reports. P&G characterized postmarket 
passive surveillance as a means of identifying and characterizing 
potential issues, including safety issues, once a product has entered 
the marketplace and been utilized by the population at large. The 
population experience with a product will be much broader than that 
derived during premarket testing because the number of individuals 
participating in premarket testing is necessarily limited. A reporting 
rate may be calculated based on the total amount of product sold and 
the number of reports received. P&G notes, however, that there are a 
number of limitations with passive surveillance reporting. For example, 
these data do not lend themselves to assessment of causality because of 
the lack of controlled conditions and various confounding factors, such 
as a high background incidence of reported GI effects. Voluntary 
reporting, such as that obtained in P&G's passive surveillance system, 
is also subject to a number of biases including the level of attention 
the subject is receiving in the news media. Because reporting is 
voluntary and subject to interpretation, and because the total number 
of ``exposures'' can only be estimated, a true incidence rate cannot be 
calculated from passive surveillance.
    Reports to P&G under its passive surveillance program for olestra 
were, for the most part, collected via calls made by consumers to a 
toll-free telephone number displayed on olestra-containing foods. Such 
calls were taken directly by P&G via its own toll-free telephone 
number. Calls were also forwarded to P&G by other snack food 
manufacturers (specifically, Frito-Lay). In some cases, information 
from such calls (but not the calls themselves) was forwarded to P&G by 
other snack manufacturers. Information was collected from callers as to 
the product used, specific product code information (where available), 
amount consumed, the nature of the complaint, symptom onset and 
duration, recurrence, characteristics and treatment, concomitant 
medications, and physician or other health professional involvement. 
Where physician contact was involved, or a medically significant event 
was reported, the petitioner attempted to obtain more detailed 
information including release of medical records for evaluation.
    Consumer reports were reviewed by trained medical affairs staff at 
P&G. Additionally, the petitioner established a committee (Olestra 
Postmarketing Surveillance Committee) of medical experts outside of P&G 
whose membership included specialists in GI disease (both adult and 
pediatric GI), epidemiology, and pharmacology to review the reports 
received, and to make recommendations about the implications, if any, 
of these reports on the safety of olestra. The petitioner submitted 
reports to FDA of complaints associated with olestra consumption 
beginning in April 1996 with the test marketing of snacks made with 
olestra.
    The petitioner reported that there were peaks in the number of 
reports received after the test marketing and

[[Page 46370]]

national introduction of olestra-containing foods. The petitioner found 
that while the absolute number of reports increased when olestra-
containing foods were first introduced into test markets, the reporting 
rate (reports per amount of product sold) declined over time. The 
petitioner also found that over time the absolute number of reports 
declined and eventually reached a plateau. The greatest number of 
reports the petitioner received over a four month period was 4,951 in 
1998 at the national introduction of olestra-containing snacks. The 
petitioner stated in its initial reports on passive surveillance that 
it is common to receive calls and complaints for products. At the start 
of national marketing the reporting rate was one report for 
approximately 100,000 servings sold, and 2 years later the reporting 
rate was one report for approximately 1 million servings sold.
    The petitioner analyzed the data from its passive surveillance 
efforts and found no trend toward increased symptoms with increased 
consumption; no trend towards increased severity with increased 
consumption; and no difference in severity by age group or gender. The 
petitioner's Olestra Postmarketing Surveillance Committee reviewed 
reports using an algorithm developed to assess the likelihood that an 
effect was caused by olestra. Using this algorithm, P&G's committee 
concluded that many reports were not likely to be related to olestra 
and no serious reports could be attributed to olestra (Docket No. 00F-
0792, submission dated March 3, 2000). Based on the nature of the 
complaints received, the petitioner designed subsequent studies to 
address, in part, issues arising from consumers' anecdotal reports 
after eating olestra-containing foods.
    In the 1996 final rule, FDA determined that the use of olestra was 
safe based on results from the preapproval safety studies. FDA stated 
in the 1996 final rule (61 FR 3118 at 3168) that P&G's plans to 
continue to study the consumption and effects of olestra were both 
prudent and responsible. FDA expected, based on results of the 
preapproval studies, that some reports concerning GI upset, such as 
loose stools and abdominal cramping, would be collected through a 
system of passive surveillance. FDA also considered that postmarket 
passive surveillance had the potential to detect low frequency and 
unexpected events because postmarket passive surveillance involves the 
entire population that consumes a product.
    FDA reviewed the reports of effects attributed to olestra and found 
that the majority of reports received concern GI effects such as loose 
stools and abdominal cramping. Other symptoms were reported at lower 
frequencies.
    FDA recognizes that passive surveillance data such as those 
collected by P&G have utility but are limited in that they do not allow 
for the determination of a causal association between the product 
consumed (i.e., olestra-containing foods) and effects reported. Such 
reports can, however, lead to hypothesis generation about why specific 
effects are occurring. This may then result in the development of 
studies used to test these hypotheses (Ref. 4).
    FDA reviewed reports of effects associated with ingestion of 
olestra that led consumers to seek medical attention. Where possible, 
the agency reviewed medical records that were obtained directly from 
individuals who reported the effect or that were obtained through P&G 
and CSPI (Refs. 5 and 6). At the 1998 FAC meeting, FDA presented its 
analysis of the medical reports received up to that time. Among the 
reports discussed was a case where a consumer had undergone an 
appendectomy and associated this with consuming an olestra-containing 
food. The pathology diagnosis at the hospital noted that there were 
minimal inflammatory changes. FDA obtained a medical release from the 
patient in order to examine the pathology slides from the appendectomy, 
which were read independently by four FDA pathologists, all of whom 
confirmed the presence of inflammatory cells throughout the wall of the 
appendix meriting a diagnosis of acute appendicitis.\14\ In many other 
of the medical records reviewed, physicians attributed patient symptoms 
to an etiology other than olestra, or did not provide an etiology. 
There were cases where physicians did attribute symptoms to olestra, 
but the limitations of passive surveillance make it difficult, if not 
impossible, to draw definitive conclusions about causality based on the 
review of individual medical records.
---------------------------------------------------------------------------

    \14\ Transcript, vol. 1, pp. 271-276.
---------------------------------------------------------------------------

3. Postmarket Surveillance Reports From CSPI
    CSPI has periodically submitted to FDA reports of effects allegedly 
associated with the consumption of olestra (Docket No. 87F-0179). The 
complaints were gathered initially in test markets by calls to an 
advertised toll-free telephone line, and gathered subsequently through 
CSPI's Internet site.
    FDA analyzed the reports from CSPI and compared the information and 
analysis to the information and analysis of the reports submitted to 
FDA by P&G. FDA noted that the reports received by CSPI were very 
similar in nature, type of complaint, and amount consumed as the 
reports by P&G.\15\ As discussed previously, passive surveillance has 
limited utility in determining causality.
---------------------------------------------------------------------------

    \15\ Transcript, vol. 1, pp. 258-270.
---------------------------------------------------------------------------

4. Comments Regarding Consumer Reports
    FDA received comments about reports of effects that consumers 
attributed to olestra. FDA considered these comments and responds in 
the following section of this document.
    (Comment 1) One comment from an individual consumer to the current 
petition reported that a family member who had Addison's disease 
suffered gastric cramps and diarrhea, laid down, went into an 
Addisonian crisis, and died after consuming olestra-containing potato 
chips. The comment did not provide any further information regarding 
the death mentioned. CSPI forwarded to the agency the medical record of 
an Addison's disease patient who had reportedly consumed olestra-
containing potato chips prior to death. The patient who died was 
diagnosed as having Addison's disease (adrenocortical insufficiency) 
and hypothyroidism in 1989. FDA believes, based on several factors, 
that the comment and medical record provided by CSPI refer to the same 
person.
    FDA reviewed the medical record forwarded by CSPI. This patient 
collapsed suddenly after experiencing a bout of gastroenteritis, and 
reportedly consumed olestra-containing chips prior to the bout of 
gastroenteritis. An autopsy showed that the adrenal glands could not be 
identified and noted a finding of Hashimoto's thyroiditis. The medical 
record did not provide any information regarding the gastroenteritis 
experienced prior to death.\16\ Due to the lack of information 
contained in the medical record, the agency was unable to determine 
whether the ingestion of olestra had any role in this patient's illness 
or death (Ref. 5).\17\
---------------------------------------------------------------------------

    \16\ The Certificate of Death lists acute cardiorespiratory 
arrest as the immediate cause of death with autoimmune 
adrenocortical deficiency syndrome as the underlying cause leading 
to the immediate cause of death. Other significant conditions 
contributing to death but not resulting in the underlying cause 
include mitral valve prolapse and Hashimoto's thyroiditis.
    \17\ FDA investigated the death mentioned in the comment. As 
part of the investigation, FDA spoke with the patient's spouse and 
the patient's co-workers about the events leading up to the 
patient's death.

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

[[Page 46371]]

    (Comment 2) A comment from CSPI to the current petition asserted 
that FDA has never conducted indepth investigations (beyond reviewing 
the medical records of a few individuals) of any of the anecdotal 
reports, including those reports involving rectal bleeding, 
hospitalization, and death. The comment further asserted that the 
agency has ignored all of the anecdotal reports and has said that there 
is no proof that any of the reports were due to olestra. The comment 
also stated that in some reports, a patient's physician attributed his/
her symptoms to olestra. The comment also quoted FDA review memoranda 
(Refs. 6 and 7) stating that olestra may have been responsible for some 
of the effects reported.
    FDA does not agree that it has ignored anecdotal reports. Nor does 
it agree that it must conduct further investigation of the anecdotal 
reports. FDA regularly reviews the reports forwarded to the agency by 
P&G and CSPI. The reports are analyzed and summarized using criteria 
such as sex, age, symptoms reported, duration of symptoms, and amount 
of olestra-containing food consumed. The agency also reviews any 
medical records forwarded with the reports. CSPI provided no evidence 
to support its allegation that anecdotal reports have been ignored. Nor 
has CSPI provided any reason to suspect that serious adverse health 
effects could have been caused by olestra. The agency will continue to 
monitor reports as they are forwarded to the agency.
    As stated in the memoranda cited by the comment, some of the 
effects reported may have been caused by olestra. These reports were 
collected using passive surveillance. As noted previously, passive 
surveillance is useful in that it can lead to hypothesis generation 
about why specific effects are occurring. These hypotheses can then be 
tested in controlled clinical trials. For example, the reports received 
from consumers attributing their symptoms to olestra served as a basis 
for some of the hypotheses tested in the petitioner's most recent 
controlled clinical studies. However, while passive surveillance data 
have utility, such data are limited in that they do not allow for the 
determination of a causal association between the product consumed and 
effects reported. Thus, based on the passive surveillance data alone, 
it is not possible to determine whether the effects reported were 
caused by consumption of an olestra-containing food.
    The agency has reviewed all of the medical records that it has 
received from CSPI and P&G about consumers who saw a physician for an 
effect attributed to the consumption of an olestra-containing food. In 
fact, FDA has conducted an investigation into the death mentioned in 
the previous comment. FDA has also obtained and examined the pathology 
slides of a patient who had undergone an appendectomy that the patient 
associated with consumption of an olestra-containing food. The agency 
has not found sufficient evidence to conclude that olestra is likely to 
have caused the symptoms that led the consumers to see a physician.\18\
---------------------------------------------------------------------------

    \18\ Ref. 5 and Transcript, vol. 1, pp. 271-276.
---------------------------------------------------------------------------

    (Comment 3) A comment from CSPI to the current petition stated that 
letters and electronic mail messages sent to P&G describing GI symptoms 
have not been included in reports that P&G submitted to the agency; 
therefore, the agency has not received all of the symptom-related 
reports. The comment recommended that the agency investigate whether it 
had received all reports.
    FDA recognizes that not every report from a consumer will provide 
enough information for FDA to determine whether an effect was possibly 
related to olestra and that some judgement is needed in compiling data. 
In light of this limitation, the agency recognizes that P&G may not 
forward all reports it receives, such as those reports containing 
incomplete information, to the agency. While this may mean that less 
than 100 percent of reports are collected, the agency has no reason to 
believe that the complaints not forwarded to the agency constitute a 
unique data set or raise an issue not previously considered. Indeed, 
the reports gathered and forwarded independently to the agency by P&G 
and CSPI are consistent in terms of the nature of the complaints and 
the amounts of olestra consumed. CSPI's comment provides no specific 
information that would lead the agency to conclude that it has not 
received an accurate and representative sample of the effects reported 
to P&G or that such reports raise an issue not already considered. 
Thus, the agency finds that there is no basis for concluding that it 
should obtain and evaluate each and every report that P&G receives.
    (Comment 4) A comment from CSPI to the current petition stated that 
the agency should obtain and disclose to the public the number of 
consumers (without identifying any particular individuals) who 
attributed their symptoms to olestra and reached an out-of-court 
settlement with the petitioner. The comment also asked for the number 
of consumers who, after attributing their symptoms to olestra, received 
or were offered reimbursement for their medical expenses. The comment 
requested that the agency consider this information in its rulemaking.
    FDA does not agree that it should obtain and disclose to the public 
the number of consumers who attributed their symptoms to olestra and 
reached an out-of-court settlement with the petitioner. Importantly, 
the comment does not demonstrate the relevance of the requested 
information to the question at issue: i.e., whether FDA should continue 
to require special labeling for olestra-containing foods. Moreover, 
settlement of lawsuits may be reached for a variety of reasons, 
including improved public relations or avoidance of unnecessary 
conflict, and do not address any factual issues regarding whether 
olestra is capable of causing the effects claimed.

C. Studies Regarding GI Effects

1. Rechallenge Study
    The petitioner submitted a report of a study designed to test 
whether individuals who complained of a GI effect after consuming 
olestra-containing snacks would have the same experience with 
subsequent exposure (Refs. 8 and 9). This test was designed to show 
whether the GI effect is consistently associated with consumption of 
the olestra-containing snack. The petitioner's study was a randomized, 
double-blind, placebo-controlled, four-period, within-subject crossover 
study. Subjects were recruited from consumers who had voluntarily 
called the snack manufacturer and reported GI symptoms associated with 
consumption of olestra-containing snacks. Each subject made four visits 
to the study site, at least 1 week apart, and was provided with 2 
ounces (oz) of either potato chips containing olestra (olestra chips) 
or potato chips containing conventional triglyceride \19\ (triglyceride 
chips). At each visit, subjects were to consume as much as they could 
of the 2 oz serving. Each participant was randomly assigned to receive 
olestra chips at two visits and triglyceride chips at two visits. 
Participants were contacted after each visit and asked whether they had

[[Page 46372]]

experienced any GI symptoms within the week after eating the potato 
chip product.
---------------------------------------------------------------------------

    \19\ In the various reports submitted by the petitioner, the 
terms triglyceride, full-fat, regular, and conventional were all 
used to describe the oil used in savory snacks. These terms mean the 
same thing. For consistency in this document, we use the word 
triglyceride.
---------------------------------------------------------------------------

    The study was completed with 98 participants, the majority of whom 
had initially called to report that they had experienced diarrhea, 
loose stools, and/or abdominal cramping (61 percent, 16 percent, and 64 
percent respectively). Approximately 48 percent of the participants 
described the symptoms that prompted their original call as severe. For 
nearly three-quarters of the participants, the amount of olestra chips 
consumed in the study was comparable to, or greater than, the amount 
associated with their initial call.
    The petitioner found that during the study there were no 
significant differences following consumption of olestra chips, 
compared with consumption of triglyceride chips, in the frequencies of 
abdominal cramping (12 percent with olestra, 9 percent with 
triglyceride), diarrhea or loose stools (11 percent with olestra, 15 
percent with triglyceride), gas (7 percent with olestra, 5 percent with 
triglyceride), or any other GI symptom (28 percent with olestra, 26 
percent with triglyceride). Overall symptom severity ratings for all 
subjects were similar after consumption of olestra and triglyceride 
chips. The petitioner concluded that this study provided evidence that 
an episode that was initially reported to be an olestra-related effect 
was in all likelihood not olestra-related, and that there was no 
evidence of a population or subpopulation with a sensitivity to 
olestra. The petitioner suggested that these results indicate that 
initial calls made to the toll-free telephone line may reflect false 
attribution of symptoms to products made with olestra.
    FDA found this study was adequately representative of the 
population who called the postmarketing surveillance system in terms of 
severity of initial symptoms and amount of olestra reportedly consumed 
prior to the initial symptom episode. FDA noted that while 98 
participants were enrolled in the study, only 92 completed all 4 
visits. The six dropouts were unrelated to olestra-related effects. 
Based on an analysis of the data in the study, FDA concluded that under 
the conditions of the study (two exposures of up to 2 oz of olestra-
containing chips separated by at least a week), subjects eating 
olestra-containing chips were no more likely to report having had loose 
stools, abdominal cramps, or any other GI symptom compared to subjects 
eating an equivalent amount of triglyceride chips (Refs. 10 and 11).
2. Acute Consumption Study
    P&G sponsored \20\ a study to determine whether there was a 
difference in the nature or frequency of GI symptoms experienced by 
subjects eating olestra chips compared to those eating triglyceride 
chips, ad libitum on a single eating occasion (Ref. 12). The study was 
a randomized, placebo-controlled, double-blind study in which 1,092 
adults and teenagers who were provided with a 13 oz bag of potato chips 
(either olestra chips or triglyceride chips) in a plain, unlabeled 
white bag, consumed as many chips as they desired while viewing a 
movie. Participants were also provided a 32-oz soft drink of their 
choice. Participants were told prior to the test that they might 
experience temporary dry mouth, thirstiness, or digestive symptoms 
(such as gas, cramping, or loose stools), as they might with salty or 
high fiber foods.
---------------------------------------------------------------------------

    \20\ The principal investigator for the study was Dr. L. 
Cheskin, Dept. of Gastroenterology, Johns Hopkins School of 
Medicine.
---------------------------------------------------------------------------

    Participants were instructed to be seated in the theater at least 
one seat apart from other participants, to eat and drink as much or as 
little of their chips and beverage as they desired, and not to share 
with anyone else. The theaters were monitored by several study staff 
during the movies. At the conclusion of the movie, participants clipped 
their bags of chips shut; noted the approximate amount of beverage 
consumed; and completed a brief questionnaire about product acceptance, 
satiety, and sensory attributes. Participants turned in the completed 
questionnaires and bags with uneaten chips and were given a toll-free 
telephone number to call if they had any questions or problems. Bags of 
chips were subsequently weighed to determine the amount consumed by 
each subject.
    Trained telephone interviewers contacted study participants and 
administered a recall questionnaire to collect information on any 
effect experienced since the movie. All subjects were specifically 
asked if they had experienced any GI symptoms during or since the 
movie, and to specify those symptoms including the severity and timing 
of any such symptoms. The study protocol specified that participants be 
contacted within 2 to 4 days of viewing the movie. The petitioner 
reported that 85 percent were contacted within 2 to 4 days and a total 
of 97 percent were contacted within a week of viewing the movie.
    The petitioner reported that the median consumption of olestra 
chips was approximately 2.1 oz (approximately 16 g of olestra) \21\ 
compared to about 2.7 oz of triglyceride chips. Overall chip 
consumption was similar across age groups, but males generally consumed 
more chips than females (median of 2.8 versus 2.1 oz, p<0.01). The 
overall palatability of the triglyceride chips was rated slightly 
higher than the olestra chips, with a mean score of 6.4 versus 5.6 on a 
9-point preference scale (p<0.01). Regarding satiety, there were no 
significant differences between the groups as indicated by mean satiety 
scores of 5.9 versus 5.7 for triglyceride chips and olestra chips, 
respectively, on a 9-point scale, with 9 being ``extremely full'' 
(p=0.07). Nor were any differences seen in beverage consumption, choice 
of beverage, or time since last meal prior to the movie between the two 
groups.
---------------------------------------------------------------------------

    \21\ In 1996, FDA estimated the probable life-time averaged 
intake of olestra at the 90th percentile to be 7.0 g/p/d. To 
evaluate subchronic conditions, FDA estimated that a ``high'' acute 
consumer of olestra (everyday for 12 weeks) would consume 20 g/p/d, 
equivalent to eating a 2 oz bag of potato chips every day, and the 
99th-percentile single-day intake of olestra for the group consuming 
the highest level of savory snacks to be 45 g/d (61 FR 3118 at 
3124).
---------------------------------------------------------------------------

    The petitioner attributed the lower chip consumption in the olestra 
group to the slightly lower preference for olestra chips reported by 
study participants. The petitioner stated, however, that the median 
consumption (2 oz) was more than a typical single-serving snack size 
bag of chips, and that approximately 100 participants ate more than 4 
oz of olestra chips (approximately 32 g of olestra).
    The petitioner reported that the proportion of subjects who 
reported GI symptoms after consuming olestra chips was not different 
from that after consuming triglyceride chips (15.8 percent and 17.6 
percent respectively). There were no differences between the olestra 
and triglyceride groups in the frequencies for 14 different self-
reported GI symptoms (gas, diarrhea, pain, cramping, upset stomach, 
loose stools, nausea, bloating, indigestion, aftertaste, eructation, 
constipation, vomiting, bloody stool), overall symptom severity for any 
GI event, nor time to onset or duration of symptoms. The petitioner 
also reported that consumption levels did not correlate with the rate 
of symptom reporting in either the olestra or triglyceride group.
    The petitioner planned to have 1,400 participants in the study and 
anticipated symptom reporting to be 10 percent for the triglyceride 
group and 15 percent for the olestra group. Using these assumptions, 
the study would provide 80 percent power for detecting

[[Page 46373]]

a 5 percent difference in the proportions of symptoms between the 
olestra and triglyceride groups. The final number of participants to 
complete the study was 1,092,\22\ which was fewer than planned. The 
rate of symptom reporting in the triglyceride group was 17.6 percent, 
which was higher than planned. Given the actual number of participants, 
and the actual rate of reports of symptoms in the triglyceride control 
group, FDA found that the study had an 80 percent chance of detecting a 
7 percent difference between the test groups (p=0.05) (Ref. 13).
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    \22\ Of the 1,742 individuals originally enrolled for the study, 
1,123 kept their appointments. Thirty-one individuals could not be 
contacted for followup, leaving a total of 1,092 evaluable subjects.
---------------------------------------------------------------------------

    FDA observed that 962 participants completed a post-movie interview 
within the 2 to 4 days goal of the study. Of the remaining 130 
participants who were contacted, 124 participants were contacted in 5 
to 10 days, 3 on the day of the movie, 1 within a day, and 2 within 23 
days. FDA noted that P&G included data from these 130 participants in 
its analysis to enhance the sensitivity of its analysis.
    FDA noted that in both the olestra and triglyceride groups, the 
most frequently reported GI symptoms were abdominal pain, diarrhea, and 
flatulence. These symptoms are also the symptoms most commonly reported 
to P&G's passive surveillance program. FDA agrees with the petitioner 
that in this study, there was no difference in the rate or severity 
reported for loose stools or abdominal cramps between subjects who ate 
olestra-containing chips and subjects eating triglyceride chips. FDA 
examined the percent of subjects reporting at different levels of chip 
consumption and found that reports of diarrhea increased for both the 
olestra and triglyceride groups with increasing consumption of chips, 
but there was no difference in the rate of reporting between the groups 
(Refs. 10 and 13).
3. Home Consumption Study
    The Home Consumption Study \23\ was designed to measure, under 
market use conditions, the effect of eating chips made with olestra on 
GI symptoms in adults and children over an extended period of time 
(Ref. 14). This double-blind placebo-controlled trial represented 1,138 
households (3,181 individuals, ages 2 to 89) randomly assigned to 
either the olestra group or the control group. To be enrolled, at least 
half the members of the household had to have eaten corn or potato 
chips at least four times in the previous month and all members of the 
household had to be willing to participate in the 6-week long study. A 
contact for each household was identified and was required to return to 
the study site once a week for 6 consecutive weeks. During each visit, 
the contact could choose from a selection of potato chips and tortilla 
chip products labeled as containing either olestra or triglyceride. The 
selection of snacks used in the study were products available in the 
marketplace presented in typical packaging. To encourage snack 
consumption, up to eight bags of chips (varying in weight from 5.5 to 9 
oz) could be selected each week. For the households in the olestra 
group, the olestra-labeled packages contained olestra chips, but for 
the control group, the olestra-labeled packages contained triglyceride 
chips. For both groups, the triglyceride-labeled packages contained 
triglyceride chips. All olestra-labeled products displayed the olestra 
label statement.
---------------------------------------------------------------------------

    \23\ Dr. R. Sandler, Professor of Medicine, University of North 
Carolina, Chapel Hill, was the principal investigator for this 
study.
---------------------------------------------------------------------------

    At each weekly visit, the contact would also provide daily records 
kept by each member of the household regarding GI symptoms. The 
household contact assisted and/or completed the form for children. The 
record consisted of a check list of eight specific GI symptoms \24\ as 
well as a field to write in any other symptoms. On each day a GI 
symptom was recorded, the subject was to rate the effect of those 
symptoms on daily activity using a scale ranging from ``noticed but did 
not affect'' to ``missed all day at work/school.'' Medication use and 
physician visits were also to be recorded.
---------------------------------------------------------------------------

    \24\ The list of GI symptoms include the following descriptions: 
(1) Heartburn or indigestion, (2) nausea or queasiness, (3) 
vomiting, (4) gas, (5) bloating, (6) abdominal cramping or pains, 
(7) more frequent bowel movements, and (8) looser stool.
---------------------------------------------------------------------------

    There were 1,620 subjects from 568 households in the olestra group 
and 1,561 subjects from 570 households in the control group. The groups 
were similar with respect to age, sex, and race. Subjects ate chips 
frequently throughout the study. The median number of days on which a 
subject consumed an olestra-labeled chip was 20 days of a possible 42 
days for the olestra group and 21 of a possible 42 days for the control 
group. The length of the study and the large number of individuals per 
group resulted in a collective period of more than 30,000 ``eating'' 
days, making it possible to detect small differences in the reporting 
of GI symptoms. The median total amount of olestra-labeled chips eaten 
over the course of the study by the olestra group (25.2 oz) was 
slightly less than that eaten in the control group (27.6 oz). During 
the 42-day study, subjects whose consumption was in the top 10 percent 
of the olestra group ate more than 59 oz of chips, while in the control 
group, the top 10 percent of the group ate more than 70 oz of chips. 
The petitioner presented data to show that the rates of olestra 
consumption achieved were beyond customary snacking by comparing the 
intake of olestra at the 90th percentile of consumption in this study 
(13.3 g/d) to Market Research Corp. of America (MRCA) preapproval 
estimates (6.4 g/d), and to data collected regarding ``real-world'' 
olestra consumption in the Active Surveillance Study (2.1 g/d). The 
petitioner concluded that the rates of consumption achieved in this 
study for both the olestra and triglyceride groups were higher than 
usual snack consumption.
    The petitioner reported that for its original planned analysis for 
the study, which examined the percentage of eating days where GI 
symptoms were reported within 2 days, olestra-containing chips resulted 
in an increase (p<0.05) in the GI symptoms of more frequent bowel 
movements, loose stools, and gas. There was no increase in reports of 
abdominal cramping or any of the other individual or total GI symptoms. 
The petitioner decided that this analysis could not be clearly 
interpreted because olestra labeled chips were eaten on numerous days 
of the study and therefore a particular GI event would be associated 
with 2 or 3 eating days.
    The petitioner presented data from an analysis that compared the 
occurrence and frequency of GI symptoms between the olestra and control 
groups. The primary response variable was the percentage of individuals 
reporting a GI event. For all subjects who consumed olestra-labeled 
products, the petitioner found that there was no difference in the 
total percentage of subjects reporting a GI symptom between the olestra 
and control groups. Of the eight GI symptoms evaluated, the only 
difference was an increased number of reports of nausea for the control 
group. For those subjects who reported a GI event, the number of 
symptom days was also compared. When the petitioner examined the data 
by days on which subjects reported symptoms, there was a small increase 
in the olestra group in the number of days when more frequent bowel 
movements were reported (3.7 days for olestra compared to 2.8 days for 
controls; p=0.04). The petitioner calculated that this increase was 
about one symptom day out of the 42 days of the study. The petitioner 
reported that

[[Page 46374]]

subjects' self assessments showed little or no impact of GI symptoms on 
subjects' daily life, and there was no increase in the percentage of 
reported severe impacts in the olestra group compared to the control 
group.
    The petitioner also examined whether there were differences in the 
incidence of reported GI symptoms among the different age groups. The 
petitioner reported that there were no significant differences in total 
or specific GI symptoms between the olestra and triglyceride groups for 
children (2 to 12 years; n=885), teens (13 to 17 years; n=227), or the 
elderly (65 to 89 years; n=402), even among the highest consumers. This 
analysis showed that for adults (18 to 64 years; n=1667), there was an 
increased percentage in reporting the GI symptom gas in the olestra 
group compared to the control group. There was also an increase in the 
number of GI symptom days, and an increase in the number of more 
frequent bowel movement symptom days, among adult subjects eating 
olestra of approximately one symptom day out of the 42 days of the 
study.
    Among adult females in the olestra group, compared to adult females 
in the control group, there was an increase of approximately one 
symptom day out of 42 days of the study with regard to more frequent 
bowel movements, gas, and any GI symptom. The only difference regarding 
reports of abdominal cramping was an increase in the control compared 
to the olestra group for adult males.
    The petitioner concluded, based on the subjects' self assessments, 
that none of these reported increases in the number of symptom days 
were meaningful because there was no impact on subjects' daily 
activities. Based on its comparison of the percent of subjects who 
reported one or more GI events during the course of the study, P&G 
concluded that there were no meaningful or serious GI effects 
associated with eating olestra-containing chips.
    At the end of the 6-week study, P&G asked participants which kind 
of chips they thought they were eating from the olestra-labeled bags. 
P&G reported that the percentage of subjects reporting GI symptoms was 
greater (approximately 50 percent) in those who believed they were 
eating chips made with olestra compared to those who thought they were 
eating triglyceride chips. This was true regardless of whether the 
participant was actually eating olestra or triglyceride chips.
    FDA employed a number of statistical approaches to best address the 
different questions to be answered by the study, and while such 
differing approaches may yield different answers, this varied approach 
provides a more complete picture of the study results. FDA analyzed 
both the temporal relationship between consumption and symptoms, and 
summation data for the study (Refs. 15 and 16).
    Examination of temporal data is important for evaluating an 
association between olestra intake and GI symptoms. Such an analysis is 
also important because in a study of this length, subjects can modify 
their eating behavior based on their experience with a product. FDA 
found that subjects in both the olestra and triglyceride groups 
modified their intake of chips as a result of experiencing more 
frequent bowel movements. FDA was able to conclude that consumers 
modify their behavior based on their experience with olestra chips by 
examining the amount of chips consumed the day before, the day of, and 
the day after a report of more frequent bowel movements. Chip 
consumption decreased after experiencing more frequent bowel movements, 
although consumption of chips did not cease.
    In order to understand the temporal relationship between olestra 
consumption and GI symptoms, FDA examined the frequency of GI symptoms 
for numerous different patterns of olestra consumption over a period of 
several days.\25\ In all these analyses, FDA found that for men, 
olestra consumption resulted in an increase in any GI symptom, gas, and 
more frequent bowel movements, and a decrease in nausea. For women, 
olestra consumption resulted in an increase in any GI symptom, gas, 
looser stools, and more frequent bowel movements. On the day that chips 
were eaten, the difference in the percentage of occasions that more 
frequent bowel movements were reported for the olestra chips compared 
to the triglyceride chips was 1.6 percent for males and 1.2 percent for 
females. These effects were seen on days of consumption of olestra 
chips but not on subsequent days on which olestra-containing chips were 
not eaten. When olestra chips were consumed on consecutive days there 
was some cumulative effect for the reports of these GI symptoms. This 
was particularly true for males. For example, the difference in the 
percentage of occasions that a report was made in the category ``any GI 
symptom'' for the olestra chips compared to the triglyceride chips 
increased from 0.9 percent on the first day to 1.7 percent on the 
second day, to 2.6 percent on the third consecutive day that chips were 
eaten and a complaint was recorded. There was also a trend for more 
frequent and recent consumption of olestra to result in a GI symptom. 
While increasing consumption of olestra and triglyceride chips both 
resulted in more symptoms, the effect of olestra was greater compared 
to triglyceride chips at all doses.
---------------------------------------------------------------------------

    \25\ These included determining the percent of occasions for 
which GI symptoms occurred on the same day and the following 2 days 
of eating an olestra-labeled chip; comparing the frequency of 
occurrence of GI symptoms on days that olestra-labeled chips were 
eaten to days that chips were not eaten to determine a ``same day of 
eating effect''; determining the percent of days on which GI 
symptoms were reported for all non-eating days in order to evaluate 
possible delayed or continuing effects of olestra; comparing the 
percent of days on which GI symptoms were reported to the number of 
consecutive days eating olestra-labeled chips in order to examine 
possible cumulative effects; for various GI symptoms analyzing the 
pattern of consumption of olestra-labeled chips for the days prior 
to the GI symptom in order to examine how the most recent day of 
eating and the frequency of eating is related to the GI symptom; for 
various GI symptoms, determining the amounts of olestra-labeled 
chips consumed on the day the GI symptom occurred (Ref. 16).
---------------------------------------------------------------------------

    In examining the effect of olestra consumption on different age 
groups, FDA found that GI symptoms were primarily seen in the 18 to 64 
age group. There were no olestra-related effects in the groups over 65 
years or younger than 18 years.
    In a separate statistical analysis, FDA focused on the sum total of 
symptom days and consumption of olestra-labeled chips over the course 
of the 42-day study (summation data). FDA analyzed the data for each GI 
symptom for both the entire study population, and for a population 
divided based on age and gender.
    In the statistical analysis of the sum total of symptom days over 
the course of the 42-day study, FDA first examined the relationship 
between the reporting of particular GI symptoms and the consumption of 
olestra-containing foods by comparing the olestra group and the 
triglyceride group. FDA found that for all study subjects (males and 
females) over the course of the 42 day study, there was an increase of 
0.28 more frequent bowel movement symptom days in the olestra group 
compared to the triglyceride group. FDA then examined the relationship 
between the reporting of particular GI symptoms and the consumption of 
olestra-containing foods by analyzing the olestra group and the 
triglyceride group separately by gender. FDA found for females in the 
olestra group, there was an increase in ``any GI symptom'' of 0.5 mean 
symptom days compared to the females in the triglyceride control. It 
was also observed that for females in the olestra group, there was an 
increase of 0.3 symptom days in more frequent bowel

[[Page 46375]]

movements over the course of the 42 day study compared to females in 
the triglyceride group. For males in the olestra group, the analysis 
showed an increase of 0.24 more symptom days for more frequent bowel 
movements compared to males in the triglyceride group.
    FDA then examined the relationship between the amount of product 
consumed and symptoms reported for all study subjects (males and 
females), and found there were associations between olestra consumption 
and reports of ``any GI symptom'' (p=0.03), loose stools (p=0.006), and 
more frequent bowel movements (p=0.002). No such associations were 
observed between the consumption of the control chips (triglyceride 
chips labeled as olestra) and any measured symptom. When analyzed 
separately by gender, both sexes showed trends for an association 
between the consumption of olestra and loose stools (males p=0.001, 
females p=0.018), and more frequent bowel movements (males p=0.001, 
females p=0.042), but only males also showed a trend for an association 
between the consumption of olestra and ``any GI symptom'' (p=0.001).
    FDA examined the relationship between the consumption of olestra-
containing foods and reports of abdominal cramping. FDA found no 
difference in the frequency of reported abdominal cramping between the 
olestra group and the triglyceride group. FDA analyzed the olestra and 
triglyceride groups separately by gender for reports of abdominal 
cramping and found no difference between males or females in the 
olestra group as compared to the triglyceride group. FDA agrees with 
the petitioner that there was no observed difference in the incidence 
or association of reported abdominal cramps between the olestra group 
and the triglyceride group (Ref. 10).
4. Stool Composition Study
    The Stool Composition Study was sponsored \26\ by the petitioner as 
a followup to the preapproval Fecal Parameters Study (discussed 
previously in section II.A.2 of this document). The study was designed 
to establish whether consumption of olestra-containing foods is 
associated with changes in clinical measures of diarrhea (water and 
electrolyte loss), effects which may be harmful, or stool consistency 
alone, which may result from adding bulk to the stool and which is not 
harmful. In addition, the study was designed to determine the 
relationship between objective measures of clinical diarrhea (e.g., 
stool water output and bowel movement (BM) frequency) and subjective 
reports of ``diarrhea'' from study subjects. The effects of olestra 
were compared to a placebo, triglyceride chips, and to sorbitol, an 
osmotically active sugar alcohol that was chosen as a positive control 
to ensure that the study methodology was adequately sensitive to detect 
increases in stool water output.
---------------------------------------------------------------------------

    \26\ The GI consultant to the study was Dr. R. Gianella, 
University of Cincinnati.
---------------------------------------------------------------------------

    The study was a single-site, randomized, double-blind, placebo-
controlled parallel clinical trial. Sixty-six subjects, ages 18 to 74, 
were housed on a metabolic ward for 12 days and consumed meals ad 
libitum. The meals conformed to the American Heart Association Step I 
diet guidelines (no more than 30 percent of calories from fat). 
Beverages were available ad libitum. All study subjects had to consume 
5 oz of potato chips eaten as two afternoon snacks. A serving of potato 
chips was either olestra (test) or triglyceride (placebo). All subjects 
were also required to consume 1.5 oz of candy made either with sorbitol 
(test) or sucrose (placebo) as a morning snack. The first two days 
(study days 1 and 2) were a lead-in period during which subjects were 
acclimated to the living conditions and the diet, and consumed placebo 
snacks (triglyceride potato chips and sucrose candies). Stool samples 
were not collected during the lead-in period. The next 4 days (study 
days 3 to 6) comprised the baseline period, in which subjects continued 
to consume placebo snacks, and all stool samples, BM ratings, and GI 
symptoms were collected. For the final 6 days (study days 7 to 12), 
subjects consumed snacks according to their randomly assigned treatment 
group, and all stool samples, bowel movement ratings, and GI symptom 
reports were collected. There were two olestra test groups (20 g and 40 
g olestra) and two control groups (positive control of 40 g sorbitol 
and placebo). The placebo group consumed two servings of placebo 
(triglyceride) potato chips and placebo (sucrose) candy. The positive 
control group consumed two servings of placebo potato chips and test 
candy (40 g sorbitol). The 20 g olestra test group consumed one serving 
of test potato chips (olestra), one serving of placebo potato chips, 
and placebo candy. The 40 g olestra group consumed two servings of test 
chips and placebo candy.
    The petitioner noted that in the study the doses of olestra were 
threefold to sixfold more than the estimated daily intake, and 10 to 20 
times more than the observed intake at the 90th percentile level in the 
Active Surveillance Study (see section III.D.1 of this document). The 
high dose, 40 g/d, was higher than the highest dose used in the 
preapproval nutrition studies (32 g/d) described previously in section 
II.A.3 of this document, in which the high dose group experienced an 
increase in GI symptoms, specifically in reported diarrhea/loose 
stools. In that preapproval study, FDA concluded that the reported 
diarrhea was not diarrhea in the medical sense because there was no 
evidence of subjects experiencing significant fluid or electrolyte loss 
(hemoconcentration, electrolyte imbalance; 61 FR 3118 at 3152-3154).
    The petitioner concluded that with regard to the critical 
parameters that are medically relevant in defining diarrhea, the 
objective measures showed that olestra did not meaningfully change 
either the total stool output or stool water output, while sorbitol 
produced large effects on both parameters. Compared to baseline, mean 
stool water output increased 9 g/d and 37 g/d for the 20 and the 40 g/d 
olestra groups respectively, and 325 g/d for the 40 g/d sorbitol group. 
Stool water output decreased 28 g/d for placebo. The measured mean 
stool water content for the sorbitol group was nearly 10 times greater 
than the group consuming the highest level of olestra and the number of 
watery BMs was 140 in the sorbitol group, one in the 40 g/d olestra 
group, none in the 20 g/d, and one in placebo. While sorbitol 
significantly increased the severity of abdominal cramping compared to 
placebo, olestra did not. The petitioner found that olestra consumption 
did not result in any clinically meaningful increases in objective 
measures of diarrhea, namely, total stool output, bowel movement 
frequency, and stool water and electrolyte output. The mean number of 
BMs for the olestra 40 g/d group was increased compared to placebo but 
was not increased compared to the olestra 20 g/d group. Subject reports 
of ``watery, difficult to control diarrhea'' did not necessarily 
correlate with measured viscosity of the stool. Olestra did increase 
stool weight in proportion to the amount eaten, and daily consumption 
of olestra gradually softened stool in a dose-responsive manner. The 
sponsor found that there was increased reporting of ``diarrhea'' in the 
olestra treatment groups during the treatment phase without an increase 
in total water output outside the normal range, i.e., the range 
observed during the baseline period and in the placebo group.
    P&G concluded, based upon the study results, that the consumption 
of olestra

[[Page 46376]]

does not cause diarrhea, but simply adds bulk and softening to the 
stool.
    FDA reviewed the data from this study and agrees with the 
petitioner's analysis, although some of the agency's analytical 
strategies differed from those of the sponsor (Ref. 17). FDA concludes 
that both comparisons of the mean after treatment and of changes from 
baseline showed dose responsive increases in stool characteristics 
(total output, water output, consistency, frequency and increases in 
water content) that were not clinically significant (Ref. 18).
    Using a 7-point scale to rate consistency of bowel movements (1 = 
watery, diarrhea; 4 = normal; 7 = hard, constipation), subjective 
ratings of stool consistency showed that subjects who ate 40 g/d 
olestra perceived their stools to be looser (mean rating 2.4) compared 
to those who ate 20 g/d olestra (mean rating 3.1). By comparison, 
placebo subjects had a mean score of 3.9 whereas those subjects in the 
40 g/d sorbitol group had a mean score of 1.5 (mean scores determined 
for days subjects consumed snacks according to their randomly assigned 
treatment group). When stool consistency was measured by peak force 
value for extrusion, both olestra groups had a lower mean stool 
consistency than placebo and the 40 g/d olestra group was lower than 
the 20 g/d group. These dose responsive findings seen among subjects 
eating olestra resulted from gradual stool softening effects observed 
after several consecutive days of olestra consumption. Although 
subjects characterized these viscosity changes as ``diarrhea,'' the 
changes were not associated with an increase in stool water.
    FDA examined the percentage of symptom days for cramping and found 
that although the 40 g/d olestra group reported an increased incidence 
of abdominal cramping compared to those in the 20 g/d olestra group 
(35.8 percent compared to 9.8 percent), this difference did not rise to 
statistical significance. The percentage of subjects reporting 
abdominal cramping in the 20 g/d olestra group appeared to decrease 
when compared to baseline or placebo (9.8 percent compared to 20.5 
percent or 18.3 percent). The 40 g/d sorbitol group had the highest 
percentage (69.8 percent) of reports of cramping. Subjects rated 
symptom severity on a scale of 0 to 5, with 0 representing none and 5 
extreme. The severity of cramps reported by subjects in the olestra 40 
g/d group was less severe than that reported by subjects in the 40 g/d 
sorbitol group (0.72 compared to 2.3). No significant olestra effects 
were found for GI symptom severity, although one individual in the 20 
g/d olestra group reported severe urgency at a rating higher than any 
other report in any of the other groups (Refs. 10 and 18).
5. Comments Regarding the GI Studies
    FDA received comments about the new GI studies. FDA considered 
these comments and responds in the following paragraphs. Comments 
regarding the label statement for GI effects will be discussed in 
section V of this document.
    (Comment 5) A comment from CSPI to the current petition criticized 
the Rechallenge Study. The comment stated that the study subjects were 
not screened for sensitivity to olestra, as was done in the preapproval 
Fecal Parameters Study. The comment also asserted that the Rechallenge 
Study contained a strong likelihood of bias because only 10 percent of 
those contacted agreed to participate in the rechallenge and those that 
did participate consumed olestra on only 2 days, at least 1 week apart, 
which reduced the sensitivity of the study. CSPI asserted that the 
Rechallenge Study also assumed that those sensitive to olestra would 
respond to it 100 percent of the time. The comment contended that those 
experiencing adverse reactions may only do so under certain 
circumstances, not 100 percent of the time.
    FDA does not agree that the selection of study subjects biased the 
Rechallenge Study nor does CSPI provide such evidence. FDA has 
determined that the subjects who participated in the Rechallenge Study 
were adequately representative of those persons who contacted the 
postmarketing surveillance system in terms of severity of initial 
symptoms and amount of olestra reportedly consumed prior to the initial 
symptom episode (Ref. 11). Further, CSPI provided no basis for its 
assertion that additional subject screening is necessary to accomplish 
the objectives of the Rechallenge Study.
    CSPI states that the sensitivity of the Rechallenge Study was 
reduced because participants consumed olestra on only 2 days, at least 
1 week apart. The conditions of the study were designed to be similar 
to the conditions under which the subjects originally reported effects 
that they attributed to consuming an olestra-containing snack. FDA 
found that for nearly three-quarters of the subjects, the amount of 
olestra consumed in the study was comparable to, or greater than, the 
amount associated with their initial symptom episode (Ref. 11). In 
addition, more than three-quarters of the subjects reported that their 
initial symptom episode occurred after a single eating occasion. 
Therefore, subjects were challenged with 2 oz of olestra chips on two 
occasions separated by a week, providing a dose and number of exposures 
comparable to, or greater than, those associated with many of the 
subjects' initial symptom episodes.
    CSPI's comment did not reference where FDA or the petitioner 
assumed that those sensitive to olestra would respond to it 100 percent 
of the time, nor is FDA aware of anyone who has put forth such a 
position. Indeed, FDA agrees that even if an individual experiences a 
reaction to olestra, that individual may not experience such reaction 
after every exposure. The Rechallenge Study shows that subjects exposed 
to olestra containing-chips were no more likely to report GI symptoms 
than when exposed to an equal amount of triglyceride chips. Thus, the 
study subjects' reactions to olestra containing-chips are not so 
frequent that they can be distinguished from their reactions to regular 
chips under the conditions of the test.
    (Comment 6) A comment from CSPI to the current petition criticized 
the Acute Consumption Study. CSPI's comment relies on its published 
letter \27\ commenting on a published study (Ref 12.) that reports data 
from the Acute Consumption Study. CSPI stated that the study may have 
failed to detect the true incidence of GI effects due to a lack of 
statistical power or inadequate controls. For example, with the 
incidence of ``any GI event'' of about 15 percent, 550 subjects in each 
group would have provided only about a 50 percent probability of 
detecting a 5 percent actual increase in the treatment group. Along the 
same lines, diarrhea and loose stools were increased less than 1 
percent in the olestra group compared to baseline levels of 2.6 percent 
and 1.1 percent, respectively. The comment asserted that maintaining 80 
percent power to detect a 1 percent increase over a 2 percent baseline 
requires about 4,000 subjects per group. The comment also contends that 
the darkened movie theater may potentially cause exposure 
misclassification (some ``olestra eaters'' may have eaten few or none 
of their chips; some ``non-olestra eaters'' may have eaten friends' 
olestra chips). The comment also stated that it took up to 10 days 
after consumption to assess symptoms. CSPI also pointed out that non-
olestra eaters consumed one-third more chips than the olestra eaters.
---------------------------------------------------------------------------

    \27\ CSPI's published letter was included in the comment as an 
attachment (Ref. 19).
---------------------------------------------------------------------------

    The criticism by CSPI of the Acute Consumption Study does not 
negate the

[[Page 46377]]

conclusion that FDA reached in its analysis of the study. The Acute 
Consumption Study was conducted to provide information relevant to 
whether olestra-containing foods should bear a label statement that 
informs consumers about the potential GI effects associated with 
olestra. FDA points out that the Acute Consumption Study was only one 
of several studies under consideration in this petition, and that the 
agency's decision on the petition is based on the totality of evidence 
in the record.
    While the petitioner's Acute Consumption Study did not achieve the 
statistical power that P&G originally desired (80 percent power to 
detect a 5 percent difference between treatment groups), the study 
still provides meaningful information concerning the effect of olestra-
containing foods on the GI system. FDA's scientific review determined 
that the study does have 80 percent power to detect a 7 percent 
difference between treatment groups (Ref. 13). The study showed that 
there was no difference in the rate or severity of loose stools or 
abdominal cramps between subjects who ate olestra-containing chips 
compared to those who ate triglyceride-containing chips.
    The comment provides no evidence that the darkened theater or the 
method used to collect symptom data affected the outcome of the study. 
As discussed previously, the study protocol was designed to minimize 
the possibility of inaccurate measurements or subjects' sharing of 
chips. For example, study participants were instructed to be seated in 
the theater at least one seat away from other participants and not to 
share their chips or beverage with anyone else. The theaters were also 
monitored by several staff during the movie.
    Similarly, the comment did not explain the effect on the study 
results, if any, from the 10-day period used to assess symptoms. After 
the movie, trained telephone interviewers contacted study participants 
and administered a recall questionnaire to collect information on any 
effects experienced since the movie. The study protocol specified that 
participants be contacted within 2 to 4 days of viewing the movie. The 
petitioner reported that 85 percent of study subjects (962 of the 
1,092) were contacted within 2 to 4 days of viewing the movie, an 
additional 124 subjects were contacted in 5 to 10 days.\28\
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    \28\ Of the remaining subjects, three were contacted on the day 
of the movie, one within a day, and two within 23 days (Ref. 13).
---------------------------------------------------------------------------

    FDA agrees that the median chip consumption for the control group 
was greater than that for the olestra group. As discussed previously, 
the Acute Consumption Study was designed to be an ad libitum study, 
allowing the investigators to examine the effects of customary or usual 
consumption. As an ad libitum study, it is possible that one group of 
subjects may consume more chips than the other. For example, the median 
consumption of chips made with olestra was 2.1 oz compared to 2.7 oz 
for chips made with conventional triglycerides. CSPI did not explain 
how the fact that one group of subjects ate more chips than the other 
affects the conclusions drawn from this study regarding the need for 
special labeling.
    (Comment 7) A comment from CSPI to the current petition criticized 
the Home Consumption Study. CSPI's comment relies on its published 
letter \29\ commenting on a published study that reports data from the 
Home Consumption Study (Ref. 14). The comment raises five issues: (1) 
The comment stated that some of the data relating to the highest decile 
of olestra consumers were overlooked; (2) the comment argued that it is 
important to focus on the small number of heavier consumers because 
most subjects ate relatively few olestra-containing chips; (3) the 
comment stated that in the highest decile of olestra consumers the 
incidence of more frequent bowel movements and loose stools was twice 
that of controls; (4) the comment stated that olestra consumers in the 
highest decile had symptoms on 18 percent of person-days, compared to 
12 percent of person-days in the control group (table 4 in Ref. 14); 
and (5) the comment pointed out that olestra consumers missed some or 
all of their activities on 0.4 percent of days, compared to 0.2 percent 
in the control group.
---------------------------------------------------------------------------

    \29\ CSPI's published letter was included in its comment as an 
attachment (Ref. 20).
---------------------------------------------------------------------------

    Prior to publication of the article concerning the Home Consumption 
Study (Ref. 14), FDA conducted its own indepth analysis of the raw data 
from the Home Consumption Study (Refs. 15 and 16) and described this 
analysis at the 1998 FAC meeting in which CSPI participated. FDA's 
analysis included an estimate of the extra symptom-days experienced by 
subjects in both the 90th and 95th percentile of olestra-containing 
chip consumption (Ref. 15). Subjects at the 90th percentile ate 64 oz 
of olestra-containing chips over the course of the study while those at 
the 95th percentile ate 83 oz of olestra-containing chips over the 
course of the study. Although CSPI alleges that the subjects in the 
study ate relatively few olestra-containing foods, the petitioner 
presented data to show that, in fact, the rates of olestra consumption 
achieved in the study were beyond usual snack consumption.
    As part of the Home Consumption Study, the investigators considered 
the effect of GI symptoms on subjects' daily activities. In its 
comment, CSPI points out that olestra consumers missed some or all of 
their activities on 0.4 percent of days, compared to 0.2 percent in the 
control group, implying that this is significant. FDA disagrees.
    CSPI does not explain how it calculated the percentage of days on 
which subjects missed some or all of their activities, nor does CSPI 
provide statistical analyses to assess whether these differences 
occurred by random chance (e.g., illness unrelated to olestra). FDA was 
able to replicate the numbers that CSPI presented and performed tests 
of statistical significance on the data. The actual number of days on 
which subjects in the highest decile missed some or all of their 
activities is very small (9 of 2,226 days in the olestra group versus 5 
of 2,646 days in the control group). Five subjects in the olestra group 
and four subjects in the control group missed some or all activities at 
least 1 day. The number of subjects missing activities and the number 
of days missed by these subjects are comparable for the olestra and 
control groups, except for one subject in the olestra group who missed 
some or all activities on 4 days (Ref. 21).\30\ From these data, it 
cannot be concluded that for the highest decile of consumers olestra 
consumption resulted in an increase in days in which consumers missed 
some or all activities. FDA believes that the Home Consumption Study, 
designed to examine the effects of ``real life'' olestra consumption, 
provides useful information relevant to the labeling of olestra-
containing foods. CSPI does not show how their analysis would change 
FDA's conclusions.
---------------------------------------------------------------------------

    \30\ Sophisticated statistical models are impractical for such a 
small number of cases. However, a Fisher's Exact test showed that 
the proportion of subjects in the olestra group who missed some or 
all activity at least 1 day was not significantly different (p-value 
of 0.73) from the proportion of subjects in the control group who 
missed some or all activity at least 1 day.
---------------------------------------------------------------------------

    (Comment 8) A comment from CSPI to the current petition criticized 
the petitioner's Stool Composition Study. The comment stated that this 
study does not negate and should not supersede the two preapproval 8-
week studies or the preapproval Fecal Parameters Study. In its comment, 
CSPI cites a 1995 FDA memorandum discussing the Fecal Parameters Study 
(Ref. 22) and asserts that the memorandum says that several

[[Page 46378]]

subjects in the study experienced high rates of water loss through 
their stool. The comment also stated that the definition of diarrhea 
used in the Stool Composition Study was too narrow and is not 
consistent with the definition used by the Centers for Disease Control 
and Prevention (CDC; three or more loose stools in a 24 hour period). 
The comment asserted that self-reporting is usually considered 
sufficient to conclude that people experience diarrhea regardless of 
demonstrated loss of electrolytes.
    In contrast to the Acute Consumption Study, the Home Consumption 
Study, and the Rechallenge Study, the Stool Composition Study was 
designed to extend the understanding of olestra's effect on stool 
characteristics that would potentially represent a safety concern. For 
this reason, the Stool Composition Study was conducted under conditions 
most likely to elicit GI effects. The highest dose of olestra provided 
in the Stool Composition Study (40 g/d) was greater than the 32 g/d 
used in the preapproval 8-week studies which was shown to cause an 
increase in GI symptoms (specifically in reported diarrhea/loose 
stools) and was twice as high as the highest dose given in the 
preapproval Fecal Parameters Study (20 g/d). Additionally, subjects' 
stool samples were collected for all 6 days of the treatment period in 
the Stool Composition Study, compared to only three days of the 7-day 
treatment periods in the Fecal Parameters Study. The Stool Composition 
Study does not negate the preapproval studies, but the results of the 
preapproval studies must be considered in light of those from the Stool 
Composition Study.
    The results of the Stool Composition Study show that olestra 
consumption does not result in any clinically meaningful increases in 
the objective measures of diarrhea. Importantly, the Stool Composition 
Study assessed the effects of olestra consumption using objective 
parameters such as total stool output, bowel movement frequency,\31\ 
and stool water and electrolyte output rather than a subject's 
subjective assessment of whether he or she experienced diarrhea. The 
use of objective measures of diarrhea is necessary to assess whether 
the ``diarrhea'' experienced by study subjects represents a safety 
concern.
---------------------------------------------------------------------------

    \31\ FDA notes that the mean bowel movement frequencies in the 
olestra-consuming groups were less than three bowel movements per 
day. The mean bowel movement frequencies were 1.6 +/- 0.2 BM/d (mean 
+/- standard error) in the 20 g/d olestra group and 2.0 +/- 0.2 BM/d 
(mean +/- standard error) in the 40 g/d olestra group (Ref. 18).
---------------------------------------------------------------------------

    FDA was concerned with the potential for olestra to cause diarrhea 
because diarrhea of medical significance is associated with excessive 
water loss and electrolyte loss, which may raise safety concerns. The 
Fecal Parameters Study memorandum cited by the comment states that the 
stool water concentration of subjects who reported having diarrhea 
during the olestra 20 g/d period did not differ from that of their 
nondiarrheal stools during the placebo period. The memorandum also 
states that although the percent of water in the stools may not have 
differed, it is possible that absolute water loss was greater in 
subjects reporting olestra-associated diarrhea because of the greater 
mass (weight) of stool passed. FDA concluded in the 1996 final rule 
that the loose stools experienced in the preapproval clinical studies 
were not diarrhea in the medical sense because they were not associated 
with loss of water or electrolytes (61 FR 3118 at 3159). The agency 
also stated that even those subjects in the 8-week studies who 
experienced loose stools or diarrhea continuously for several weeks 
during olestra consumption did not show any evidence of fluid loss such 
as hemoconcentration or electrolyte imbalance. Thus, the agency 
determined that olestra-related GI effects were not adverse health 
effects (61 FR 3159). The results of the Stool Composition Study 
confirm the agency's 1996 decision that the GI effects resulting from 
olestra consumption do not represent adverse health effects, regardless 
of the terminology (diarrhea or otherwise) used to describe these 
effects.

D. A Study Regarding Nutritional Effects--Active Surveillance

    As discussed previously in section II of this document, olestra is 
neither digested nor absorbed, and as such, passes intact through the 
digestive tract where it can interact with fat-soluble dietary 
components present in the gut at the same time. Fat-soluble nutrients 
and components tend to partition or dissolve into the olestra, thereby 
reducing the absorption efficiency of these substances (61 FR 3118 at 
3144-3149). Olestra does not interfere with the absorption of macro-
nutrients (protein, carbohydrates, and fats) or water-soluble nutrients 
(61 FR 3118 at 3149-3152). The clinical studies conducted in support of 
the 1996 final rule examining the effect of olestra on fat-soluble 
components of the diet were performed under conditions that maximized 
the interaction of olestra with these dietary components, i.e., olestra 
was incorporated into foods eaten at every meal. These studies were not 
designed to examine effects from the usual or customary consumption of 
savory snacks made with olestra (see section II.A.3 of this document).
    To compensate for the effect of olestra on the absorption of the 
fat-soluble vitamins A, D, E, and K, FDA required that these vitamins 
be added to olestra-containing foods. The level of addition was chosen 
to ensure that there would be neither a reduction in the absorption of 
fat-soluble vitamins from the diet, nor an increase in vitamin levels 
due to the presence of the added vitamins in the olestra-containing 
foods (see section II.A.3 of this document). Although FDA noted that 
olestra interferes with the absorption of carotenoids, FDA found no 
scientific basis for requiring the addition of any carotenoid to 
olestra-containing foods (61 FR 3118 at 3147-3149).
    As outlined by the petitioner in its January 24, 1996, letter to 
the agency, P&G established a program of active surveillance. A report 
of this surveillance with results and analysis from the first year at 
the sentinel site was submitted to the agency on April 15, 1998. 
Additionally, the agency has continued to review and evaluate new data 
and information that bear on the safe use of olestra, such as new data 
and information on the health significance of carotenoids.
1. Active Surveillance Study by P&G
    The petitioner provided funding to investigators at the Fred 
Hutchinson Cancer Research Center in Seattle, WA, to design and 
implement a multi-year, Active Surveillance Study to monitor patterns 
of use of olestra-containing savory snack products and to collect blood 
samples to measure nutrient status (Ref. 23). The study had three 
specific goals: (1) To monitor adoption and patterns of use of olestra-
containing savory snack products in representative samples of the U.S. 
population; (2) to assess the association between the introduction of 
olestra-containing savory snacks and serum concentrations of 
carotenoids and fat-soluble vitamins in representative cross-sectional 
samples of the U.S. population; and (3) to assess the long-term 
association between consumption of olestra-containing savory snacks and 
serum concentrations of carotenoids and fat-soluble vitamins among a 
cohort of olestra consumers.
    The study has three components corresponding to the three specific 
aims. The first component, called the population cross-section, was a 
telephone survey used to monitor the prevalence and patterns of 
olestra-containing savory snack consumption,

[[Page 46379]]

fruit and vegetable consumption, and triglyceride savory snack food 
consumption by consumers. Demographic information was collected as 
well. A telephone survey was conducted in each of the study sites 
before olestra-containing snacks were marketed. Subsequent yearly 
surveys were completed after olestra-containing snacks were introduced 
to the market.
    A random sample of participants in each telephone cross-section 
sample was recruited into the second component, a clinical cross-
section. The clinical cross-section was an investigation of the 
relationships among nutrient intake, olestra consumption, and serum 
nutrients. Study participants visited a clinic to provide further 
information, including dietary information, medical histories, and 
blood samples. Followup telephone interviews included questions about 
usual fruit, vegetable, and snack food use during the previous month, a 
24-hour dietary recall to measure co-consumption of fruits and 
vegetables with savory snacks, health symptoms and status, and a short 
household food inventory.
    Within the clinical cross-section, information on olestra intake 
was used to select olestra users from non-users to be recruited into 
the third component of the Active Surveillance Study, i.e., the 
clinical cohort study. The clinical cohort study was an investigation 
of the relationships among nutrient intake, olestra consumption, and 
changes in serum nutrients over time. Participants in the clinical 
cohort are a subset of those people who participated in the Year 0 
clinical cross-section and were monitored annually over the course of 
the Active Surveillance Study. The clinical cohort was designed to have 
an over-representation of consumers of olestra-containing snack food. 
The design for the clinic visit and the information gathered is the 
same as for the clinical cross-section.
    The study was conducted in four U.S. cities. As of the publication 
of this document, data are available only from the sentinel site, 
Marion County, IN, where test marketing began in 1997.\32\ The study 
began one year later in the other cities, because national marketing of 
olestra-containing foods in those areas began later.
---------------------------------------------------------------------------

    \32\ The other three cities in the Active Surveillance Study 
were Baltimore, MD, San Diego, CA, and Minneapolis, MN.
---------------------------------------------------------------------------

    The first component of the active surveillance is the population 
cross-section. A random-digit-dial telephone survey of Marion County, 
IN, residents was completed before olestra-containing foods were 
marketed in that area (February 1997). This survey (Year 0) included 
1,962 adults, aged 18 years and over. The second telephone survey was 
completed after olestra-containing foods were introduced to the local 
market (between August 1997 and January 1998). This survey (Year 1) 
included 1,525 adults, aged 18 years and over. Based on the Year 1 
data, which are weighted to be representative of the Marion County 
population, 15.5 percent of adults reported eating olestra-containing 
snacks one or more times per month with the median frequency being 
three times per month. Ninety percent of adults reported eating one or 
more servings of fruits and vegetables per day, thus providing a basis 
for assessment of any effects on dietary carotenoid absorption. Intake 
of fruits and vegetables and intake of total snacks did not change in 
the population cross-section between Year 0 and Year 1. Olestra-
containing snack food introduction was not associated with an overall 
increase in savory snack consumption or with a decrease in fruit and 
vegetable intakes. There was a modest decrease in consumption of 
reduced- and non-fat savory snacks at Year 1 compared to Year 0.
    Blood sera from study subjects, in both the cross-sectional and 
clinical cohorts, were analyzed for vitamins A, D, E, and K, total 
cholesterol, high density lipoprotein (HDL) and triglycerides, and the 
six major carotenoids that represent more than 90 percent of the 
circulating carotenoids (alpha and beta carotene, lycopene, lutein, 
zeaxanthin, and beta-cryptoxanthin). The study investigators then 
compared these serum measures based on olestra intake. Four olestra 
consumption groups were defined: (1) None; (2) low (less than 0.4 g/d 
of olestra, which is less than the 60th percentile of consumption); (3) 
medium (between 0.4 and 2.0 g/d of olestra, which is between the 60th 
and 90th percentiles of consumption); and (4) high (greater than 2 g/d, 
which is greater than the 90th percentile of consumption).
    Results from the cross-sectional study comparing 1,252 subjects in 
year 0, and 1,164 subjects in year 1, show that with increasing olestra 
intake, there were significant trends for an increase in vitamin K 
levels (p = 0.013) and a decrease in serum cholesterol (p = <0.05). 
There were no significant differences or trends found for other 
vitamins or for total carotenoid or individual carotenoids that could 
be associated with olestra consumption.
    For the clinical cohort (477 study participants), the sponsor 
reported that for the entire cohort from year 0 to year 1, there was a 
decrease in mean serum concentrations of total carotenoids, as well as 
in concentrations of retinol, 25-OH vitamin D, lycopene, lutein, and 
zeaxanthin, and an increase in beta-cryptoxanthin. Tests of association 
between olestra consumption and changes in serum concentrations of fat-
soluble vitamins and carotenoids were based on regression models that 
included variables to characterize the four levels of olestra 
consumption. However, these changes were not related to the amount of 
olestra consumed. A trend was observed for increased vitamin K, but the 
change did not reach statistical significance (p = 0.087). There were 
no changes observed for the other vitamins.
    The petitioner cautioned that the results discussed previously 
reflect data from only the first year that olestra products were 
marketed, and that data were available from only a single site. With 
these caveats, the petitioner reached the tentative conclusion that it 
appeared that the consumption of olestra-containing foods in the 
marketplace had little, if any, effect on the status of fat-soluble 
vitamins and nutrients as measured by serum concentration.
    FDA notes that survey results show that the co-consumption of 
savory snacks (made with or without olestra) with a fruit or vegetable 
was relatively rare. Overall, less than 15 percent of total carotenoids 
were consumed with any savory snack. Olestra's effect on the absorption 
of fat-soluble carotenoids is greatest when co-consumed with the source 
of the carotenoid. Interference with absorption of carotenoids 
diminishes and then disappears as the time between eating an olestra-
containing food and a carotenoid-containing product increases.\33\
---------------------------------------------------------------------------

    \33\ The precise length of time olestra interferes with 
absorption varies with the dose of olestra, and also varies somewhat 
from individual to individual, as GI transit time is variable among 
individuals (61 FR 3118 at 3144).
---------------------------------------------------------------------------

    In the clinical cross-sectional sample, 217 of 947 individuals 
reported eating at least one olestra-containing food in the previous 
month with a median intake of 8.1 g of olestra per month. The 90th 
percentile consumption level was 64 g of olestra per month. Of the 402 
clinical cohort participants who were considered consumers of olestra, 
only 139 reported eating any olestra-containing foods in the previous 
month. The median frequency of eating olestra-containing foods for this 
group of consumers was 1.01 times per month with a median intake of 
11.9 g of olestra per month. The 90th percentile

[[Page 46380]]

frequency of eating olestra-containing foods was six times per month 
with a 90th percentile intake total of 70.6 g of olestra per month.
    FDA notes the infrequent and small olestra ingestion reported in 
the study. These reports are drawn from participants' ``real-life'' use 
of snacks made with olestra. FDA evaluated whether there were changes 
in serum levels of carotenoids and fat-soluble vitamins from year 0 to 
year 1 in the clinical cohort. FDA also evaluated whether olestra 
consumption was associated with changes in serum carotenoid status and 
fat-soluble vitamins. FDA noted the various changes in serum measures 
(a drop in total serum carotenoids as well as in concentrations of 
vitamins A and D, lycopene, lutein, zeaxanthin, and an increase in 
beta-cryptoxanthin) seen in the clinical cohort group from year 0 to 
year 1. FDA also noted that there is a lack of association in the 
clinical cohort between olestra ingestion and any nutrient changes, and 
therefore, the changes are unlikely to be caused by olestra consumption 
(Ref. 24).
2. Comments Regarding the Active Surveillance Study
    FDA received comments about the Active Surveillance Study. FDA 
considered these comments and responds in the following paragraphs.
    (Comment 9) Comments from CSPI and academia to the current petition 
asserted that P&G's Active Surveillance Study showing that olestra 
consumption produced no change in carotenoid levels provides little 
useful data because the subjects consumed only small amounts of 
olestra. CSPI stated that study subjects consumed no more than 2 g of 
olestra/day (approximately one-fourth to one-fifth of a serving of an 
olestra-containing snack per day) and only about 15 percent of adults 
in the study ate at least one olestra-containing snack per month. The 
comment from academia stated that any assumption about the effects of 
olestra on blood carotenoid levels should be based on the strong 
likelihood that at least some individuals will consume 1 to 4 oz of 
olestra-containing potato chips on a daily basis, the effects of which 
are addressed in the preapproval studies.
    The Active Surveillance Study is only one piece of information in 
the current petition. It was designed to assess the effects of olestra 
consumption on serum carotenoids and fat-soluble vitamins under 
customary or usual consumption conditions. As such, it complements the 
preapproval studies, which were conducted using consumption scenarios 
designed to assess the safety of olestra's effects on serum carotenoids 
and fat-soluble vitamins. The highest dose of olestra consumed in the 
preapproval studies was 32 g/d, which is equivalent to eating 
approximately 4 oz of olestra-containing chips; in contrast to the 
Active Surveillance Study, in the preapproval studies olestra was 
consumed in a variety of foods for which it is not approved for use. 
FDA noted in the 1996 final rule that it was likely that olestra's 
effects on carotenoid absorption would be substantially less than those 
observed in the 8-week studies (61 FR 3118 at 3149). Under the 
conditions of the 8-week studies, which were designed to assess safety, 
FDA found supplementing olestra with vitamin A to compensate for the 
provitamin A function of beta-carotene addressed the possible safety 
concerns about carotenoid loss in olestra-containing foods. The 
comments provide no evidence to contradict FDA's 1996 conclusions.
    FDA agrees that P&G's active surveillance did not identify high 
levels of olestra consumption. Importantly, however, the levels of 
olestra consumption identified in P&G's Active Surveillance Study 
provide information about customary or usual consumption which is 
relevant to the labeling issue raised by this petition.

E. Consultations and Literature Review Regarding Nutritional Effects

    FDA considered data and information that became available after the 
1996 decision in assessing whether the scientific understanding of the 
possible human health benefits of carotenoids has changed since FDA's 
1996 decision, and whether new information should be reflected in the 
label statement.
    The petitioner conducted a literature review of all peer reviewed 
articles published between January 1996 (when the 1996 final rule was 
published) and May 1998, just prior to the FAC meeting, concerning 
possible health effects of carotenoids. This review included more than 
200 references to carotenoids and their possible role in human health 
(Refs. 25 and 26). The petitioner's conclusion was that the reviewed 
data did not establish that consumption of carotenoids confers 
protection from disease.
    FDA considered data and information discussed at the 1998 FAC 
meeting. The petitioner presented its review of the scientific 
literature on carotenoids and human health. The petitioner sponsored a 
study that was presented to the FAC that found no significant 
association between macular pigment density with olestra intake. The 
researchers testified that the relationship between the carotenoid-rich 
macular pigment and the disease process was yet to be understood.\34\
---------------------------------------------------------------------------

    \34\ Transcript, vol. 2, pp. 197, 201, 210.
---------------------------------------------------------------------------

    At the FAC, the petitioner called upon Dr. Gilbert Omenn \35\ to 
present results from intervention studies with beta-carotene.\36\ These 
studies indicated that there was an association between beta-carotene 
intake and increased risk for lung cancer within the study groups.
---------------------------------------------------------------------------

    \35\ At the time Dr. Omenn was Executive VP Medical Affairs and 
CEO, University of Michigan Health System and was a principal 
investigator for the CARET study.
    \36\ Transcript, vol. 2, pp. 154-160.
---------------------------------------------------------------------------

    During the open public hearing portion of the FAC meeting, a number 
of individuals that the petitioner invited as experts spoke about the 
potential role carotenoids play in human health and expressed the view 
that carotenoids do not explain the cancer preventive effect of fruits 
and vegetables.\37\
---------------------------------------------------------------------------

    \37\ Transcript, vol. 2, pp. 32-34, 42-44.
---------------------------------------------------------------------------

    At the FAC meeting, CSPI, and the individuals they called upon as 
experts, asserted that a consensus had been developing among the 
scientific community that carotenoids are likely to reduce the risk of 
certain chronic diseases. For example, Dr. Graham Colditz of Harvard 
Medical School said that a low intake of carotenoids is associated with 
an increased risk of cardiovascular disease and certain cancers.\38\
---------------------------------------------------------------------------

    \38\ Transcript, vol. 2, pp. 233-247.
---------------------------------------------------------------------------

    Most members of the FAC expressed the view that epidemiological 
data show a decreased risk for certain chronic diseases and cancer with 
increased intake of fruits and vegetables. The increased intake of 
fruits and vegetables is associated with an increased serum level of 
carotenoids (which are a component of fruits and vegetables), but it is 
yet to be determined what, if any, specific role carotenoids play, and 
at what level they may be required in the diet.\39\
---------------------------------------------------------------------------

    \39\ Transcript, vol. 3, pp. 102-174.
---------------------------------------------------------------------------

    The Panel on Dietary Antioxidants and Related Compounds, Food and 
Nutrition Board, Institute of Medicine (IOM), National Academy of 
Sciences (NAS) published a report in 2000 (Ref. 27). The panel that 
produced the report considered dietary antioxidants and other compounds 
to assess the required daily intakes for these nutrients. The NAS panel 
noted that there is a considerable body of research relating blood 
levels of carotenoids with a lower risk for some chronic diseases. 
However, the NAS panel concluded that this evidence did not support a 
requirement for carotenoid intake because the observed effects may be 
due

[[Page 46381]]

to other factors related to fruit and vegetable intake. Intervention 
studies designed to test whether carotenoids (specifically beta-
carotene) had any direct protective benefits for health did not show 
any benefit compared to the control (placebo supplement), and indicated 
that there was an increased incidence in disease (lung cancer) for 
certain at-risk sub-populations (smokers). The panel did not propose 
establishing a dietary reference intake (DRI) for beta-carotene or any 
other carotenoid (Ref. 27).
    FDA considered the NAS report on carotenoids and concluded that the 
evidence concerning carotenoids and the conclusions that could be drawn 
from the evidence about carotenoids and human health had not 
substantially changed since the 1996 decision. FDA acknowledges that 
investigations are continuing on carotenoids to better understand 
biochemical mechanisms and genetic controls of these substances, and 
what, if any, role carotenoids have in human health (Ref. 28).
    In the fall of 2000, FDA consulted with the NEI for an update as to 
whether there had been a change in the understanding of the science 
regarding lipophilic carotenoids and eye health since FDA last 
consulted with NEI on this question prior to the 1996 final rule (Ref. 
29). The NEI said that no specific vitamin or carotenoid had been 
established as protective against macular degeneration (Ref. 30). The 
NEI also said that the ongoing ``Age-Related Eye Disease Study'' 
(AREDS) includes a randomized clinical trial of an antioxidant 
combination (beta-carotene, Vitamins C and E) or zinc that is 
evaluating the effect of these nutrients on macular degeneration and 
cataracts.\40\ Other investigations continue to explore the hypothesis 
that oxidative damage to the retina increases the risk of macular 
degeneration and that antioxidant nutrients and carotenoid pigments 
concentrated in the macula may protect against this damage (Ref. 30).
---------------------------------------------------------------------------

    \40\ Since FDA's consultation with the NEI in the fall of 2000, 
the ongoing AREDS study published a report of a randomized clinical 
trial of an antioxidant combination (beta-carotene, Vitamins C and 
E) or zinc evaluating the effect of these nutrients on macular 
degeneration and cataracts (Ref. 31). Results of the study showed 
that a combination of antioxidants (vitamin C, vitamin E, beta 
carotene) and zinc reduced the probability for the development of 
advanced age-related macular degeneration (AMD) in study subjects 
who were at high risk for developing AMD. The groups given only 
antioxidants, or only zinc, did not show this reduction in rates of 
at least moderate visual acuity loss.
---------------------------------------------------------------------------

F. Consumer Perception Studies of the Label Statement

    P&G and Frito-Lay submitted data from studies designed to test 
consumer understanding of the label statement required by the 1996 
final rule as comments to that final rule. Additional reports of 
testing, conducted after the original comment period for the label 
statement closed on April 1, 1996 (61 FR 3118 at 3160), were also 
submitted to the agency. These reports are discussed in the following 
paragraphs.
1. 1996 Consumer Studies
    On April 1, 1996, P&G submitted consumer studies conducted on the 
label statement required on olestra-containing foods. These studies 
were completed before olestra-containing foods were available in the 
marketplace. The petitioner did both qualitative (focus group) and 
quantitative (mall intercept, detailed questionnaire) testing. The 
objective of the qualitative research was to determine how consumers 
comprehended the required label statement and to develop potentially 
more informative label statement(s) for use in subsequent quantitative 
research. The objective of the quantitative research was to understand 
how the required label statement and alternative label statements 
communicate to consumers, to understand issues raised by the various 
label statements, and to understand how the label statements affect 
consumers' understanding of olestra-containing snack foods.
    In the qualitative research, three focus group sessions were 
conducted in each of three cities (total of nine focus group sessions) 
among adults or teens. Participants saw a realistic product package and 
several possible versions of the olestra label statement, and were told 
that a version of these statements might appear on product packages. 
Participants discussed their impressions of the product and the various 
label statements in their own words. The group went through each label 
statement line by line.
    In the quantitative research, a detailed questionnaire was 
presented to 1,726 respondents, adults and teens, recruited at shopping 
malls at 40 different sites around the country. Respondents were 
randomly assigned to a group to assess one of four conditions for 
wording or presentation of the label statement. Respondents were shown 
the assigned information statement on a realistic product package that 
included a nutrition facts panel, ingredient list, and other product 
information. They then answered questions about the product, the 
information statement, and the effects of olestra.
    The petitioner concluded from these studies that the required label 
statement did not communicate clear and understandable messages to 
consumers. The petitioner found that most participants in the studies 
were confused by label statements about both the GI effects and the 
nutrient effects.
    The petitioner asserted that the data demonstrate that consumers, 
after reading the ``vitamins added'' portion of the required label 
statement, are left with the impression that eating olestra-containing 
foods will change their vitamin status. After reading the nutrient 
statements, some participants inappropriately concluded that olestra is 
not safe based on presumed vitamin effects. The petitioner stated that 
the qualitative research indicated that when participants understood 
that there are no net consequences on vitamins A, D, E, and K, the 
participants questioned the need for any statement or were suspicious 
of the statement. The petitioner stated that this study shows that 
consumers find the concept of nutritional effects and compensatory 
addition difficult to comprehend without extensive amounts of 
information. The petitioner concluded from the results of the 
quantitative studies that a simple label statement indicating that the 
vitamins in the ingredient statement do not provide a nutritionally 
significant source best communicates to consumers the fact that there 
would be no effect on their status of vitamins A, D, E, and K.
    Also, the petitioner concluded that the term, ``other nutrients,'' 
appears to provide no meaningful information to consumers. The 
petitioner reported that a majority of participants concluded that 
there were no effects on other nutrients regardless of whether the 
label statement cited effects on ``other nutrients.'' For those 
participants who did notice the message, they incorrectly concluded 
that a variety of nutrients, some known not to be affected by olestra 
(for example, vitamins C and B) were, in fact, being affected.
    The petitioner stated that results from the focus group study on 
the GI portion of the label statement showed that the currently 
required label statement may cause consumers to incorrectly attribute 
GI symptoms to the consumption of olestra, including GI symptoms that 
olestra does not cause and GI symptoms that are not listed on the label 
statement. The petitioner said that the research supports the 
conclusion that the label statement may cause consumers to wrongly 
attribute symptoms because participants

[[Page 46382]]

interpreted the label statement in the context of their experience with 
other foods that are not labeled. Because there are other foods that 
cause GI symptoms but are not labeled (e.g., psyllium,\41\ wheat fiber, 
and beans), consumers infer from the olestra label statement that 
olestra's effects must be worse. The petitioner characterized a typical 
participant reaction during the focus group testing to be, ``If it's 
like my other experiences, then why does it have this label?''
---------------------------------------------------------------------------

    \41\ FDA assumes that the term ``psyllium'' refers to the 
soluble fiber component of the psyllium husk that is the subject of 
the agency's regulation in part 101 (21 CFR part 101) authorizing a 
health claim for soluble fiber from certain foods and coronary heart 
disease (Sec.  101.81). FDA considers both ``psyllium seed husk'' 
and ``psyllium husk'' to be common or usual names for this 
substance, but uses the term ``psyllium'' where it was used by the 
petitioner or comments.
---------------------------------------------------------------------------

    The petitioner found that a label statement with an explanation of 
why olestra might cause GI effects (``Because olestra is not digested, 
it may cause intestinal discomfort or a laxative effect.'') added 
significantly to participant understanding. When specific symptoms were 
mentioned, such as ``loose stools'' and ``abdominal cramping,'' more 
participants responded that they would expect those GI symptoms, 
compared to panelists who viewed statements that did not mention 
specific symptoms. The petitioner also found that general GI symptom 
terms, such as ``laxative effect'' and ``intestinal discomfort'' 
communicate the same expectations in GI changes as the specific terms 
for other GI symptoms, especially for the range of symptoms related to 
stool changes.
    The petitioner also investigated consumer reaction to the boxed 
configuration of the label statement, and concluded that statements not 
boxed had less connotation of harm.
    Frito-Lay, an interested party and producer of olestra-containing 
snack foods, also submitted to the agency results from consumer studies 
on the label statement conducted prior to marketing of olestra-
containing foods (sent as comments to Docket No. 87F-0179, dated March 
28, 1996, and March 29, 1996). The purpose of these studies was to test 
the effect and communication value of the required label statement and 
alternative statements developed by Frito-Lay. The same type of 
methodology described above for the quantitative assay was used to 
obtain responses from 1,183 individuals from 5 sites around the 
country. Respondents were shown a label statement and then asked, based 
on this label statement, whether they believed that products containing 
olestra were safe. Frito-Lay said that in response to all the tested 
label statements, including the required statement, most respondents 
were uncertain as to the safety of olestra (66 to 71 percent), or 
thought it unsafe (14 to 19 percent). Because none of the label 
statements Frito-Lay tested eliminated consumer misconception about 
safety (including a label statement declaring that olestra has been 
found safe for consumption by the FDA), Frito-Lay concluded that there 
should be no special label statement. Additionally, Frito-Lay found 
that 63 to 65 percent of respondents believed that some people would 
experience GI discomfort. About half of these respondents said that 
they would delay going to a doctor if they ate a product containing 
olestra and then experienced GI discomfort for which they would 
normally seek medical attention. Additionally, a majority of the 
respondents (68 to 71 percent) believed that olestra would decrease the 
level of vitamins A, D, E, and K in their bodies, and a majority 
believed that other nutrients are affected by olestra.
    FDA reviewed the consumer perception studies submitted in 1996 by 
P&G and Frito-Lay (Ref. 32). FDA noted that the studies were an attempt 
to evaluate what the olestra label statement communicated to consumers 
regarding several issues. These issues include the following subjects: 
(1) The safety of olestra; (2) whether the portion of the label 
statement about GI effects communicates reasonable expectations about 
the severity, frequency and duration of potential symptoms, and whether 
alternate wording or presentations communicate more effectively; and 
(3) whether the portion of the label statement about the potential 
nutrient absorption effects of olestra effectively communicates the 
reason for the addition of vitamins A, D, E, and K, as well as the 
scope and potential severity of the consequences of eating olestra, and 
whether alternate wording or presentations communicate more 
effectively.
    FDA found the mall intercept studies to be adequate in methodology 
and sample size to differentiate between the communication 
effectiveness of the statements tested, including such changes as 
alternate wordings, or separation of portions of the label statement. 
For example, in part of Frito-Lay's quantitative study, participants 
were asked about the safety of olestra before, as well as after, 
viewing the test label statement. This use of a question before viewing 
the label statement serves to measure the impact of the label statement 
on participants' opinions or whether that opinion was established prior 
to viewing the label statement. However, the studies were limited to 
some extent by the choice and wording of questions. For example, P&G's 
quantitative study did not include, as a control, a ``no information'' 
statement, so the communication value of simply having a statement on 
the product package cannot be evaluated.
    Regarding the safety of olestra, FDA found that the results of the 
consumer perception studies conducted by the petitioner and by Frito-
Lay show that the label statement is misunderstood by respondents and 
thought to be a warning about possible health consequences of olestra 
consumption. FDA notes that Frito-Lay's data demonstrate that there was 
an increase in the level of concern about the safety of olestra after 
participants read a label statement. Specific wordings or presentations 
contributed little to the level of expressed concern. Only when a label 
statement included wording that FDA has found olestra to be safe for 
consumption was some of the concern alleviated. FDA also noted that 
when participants were given the opportunity to respond to the question 
of whether olestra is safe by opting for ``uncertain,'' a majority 
chose this response to every label statement examined. When response 
options were limited to yes or no, the majority chose ``no'' (i.e., not 
safe).
    Regarding GI symptoms, FDA concluded that there was no indication 
from these studies that consumer expectations about the severity, 
frequency, or duration of GI symptoms was influenced by specific 
wording or qualifications on effects or by whether there were any 
directions about when to contact a physician. There also was no 
indication from these studies that consumers' expectations about the GI 
symptoms were influenced by whether the nutrient portion of the label 
statement was present. Participants tended to use the same words used 
in the label statement to describe potential symptoms (i.e., loose 
stools, abdominal cramping), but alternate words to describe certain GI 
effects (loose stools, more frequent bowel movements, diarrhea) were 
all understood to mean the same thing. When asked what proportion of 
the population might experience symptoms, modifiers had little effect 
on respondents' answers.
    Regarding the nutrient absorption portion of the label statement, 
FDA found that the results of the 1996 consumer perception studies show 
that the current label statement is not effective in explaining the 
rationale for and quantitative consequences of adding the four fat-
soluble vitamins to

[[Page 46383]]

olestra-containing foods. Respondents' knowledge about olestra's 
ability to interfere with the absorption of fat-soluble components of 
the diet was not tested directly, so it is not possible to assess the 
role that prior knowledge has in respondents' interpretation of the 
label statement.
    The studies demonstrate that consumers do not understand that the 
addition of the vitamins was intended to produce no net effect in the 
body. The studies also show that respondents tended to believe that the 
statement about the inhibition of absorption applied to many other 
nutrients, including those on which olestra has no effect.
    Without the absorption statement, somewhat fewer respondents 
believed that vitamin A, D, E, and K levels would be changed by 
consuming olestra, but fewer respondents were also aware that olestra 
reduced the absorption of these vitamins. Even without an absorption 
statement, substantial fractions of respondents believed that consuming 
olestra-containing foods would change both fat-soluble and fat-
insoluble vitamin levels, presumably because of prior beliefs about 
olestra. Variations on the wording of the portion of the label 
statement regarding vitamin absorption and addition made consumers more 
aware of the vitamin absorption effect of olestra, but none remedied 
the miscommunication.
    FDA concludes, based on this work, that neither the current label 
statement nor the alternative label statements tested on product 
packaging clearly communicate to consumers the effect of olestra on 
vitamin absorption. Without more detailed information or familiarity 
with olestra, consumers drew inappropriate inferences about the scope 
and magnitude of the additive's effect on vitamin absorption.
2. 1999 Consumer Studies
    In 1998 and 1999, the petitioner conducted quantitative consumer 
research using a detailed questionnaire, and submitted the study to the 
agency on April 22, 1999 (Docket No. 00F-0792). The petitioner's stated 
purpose for this study was to obtain quantitative data on consumer 
perceptions of the required label statement. Participants were asked to 
respond to a series of questions regarding safety and GI effects after 
reading the required label statement.
    The petitioner reported that 61 percent of participants thought 
that the products bearing the required label statement were unsafe.\42\ 
The same percentage believed that the label statement was the 
government's way of telling them that the product was unsafe. A 
majority viewed the label statement as a warning, and not as an 
information statement. After reading the label statement, 83 percent of 
respondents believed that they could experience symptoms after eating a 
handful of chips, and approximately a quarter of these respondents 
would attribute extremely serious symptoms to olestra (severe diarrhea 
lasting several days, bloody stools, or vomiting lasting up to several 
days). The petitioner noted that extensive clinical data on olestra 
show that the additive does not cause such symptoms. The petitioner 
concluded from the results of this study that the label statement is 
misleading and conveys messages to consumers that are not consistent 
with the total body of clinical data on olestra or with FDA's intention 
in requiring the label statement.
---------------------------------------------------------------------------

    \42\ By comparison, in the 1996 survey 45 percent of 
respondents, after viewing the required label statement, considered 
products containing olestra to be unsafe (Ref. 33).
---------------------------------------------------------------------------

    P&G also sought to assess consumer perceptions about the current 
and alternative label statements. Twenty alternative label statements 
were tested and rated on a scale of 1 to 9 for the degree of safety 
perceived from the label statement (1 is ``not at all safe,'' 9 is 
``very safe''). For the GI portion of the label statement, P&G reported 
that respondents' perception of the degree of safety of olestra-
containing foods after viewing the alternative GI statements ranged 
from 3.8 to 6.8. Alternative GI statements that provided a familiar 
frame of reference (comparison to beans, or onions for example), or 
that stated that GI symptoms were not a likely consequence, resulted in 
a greater perception of safety than those statements that provided 
generalized GI symptom data or context to qualify or describe GI 
symptoms. In this study, P&G found that the statements that elicited 
the lowest perception of safety were statements that specified GI 
symptoms, including those that are in the current label statement. For 
the nutrient portion of the label statement, P&G reported that more 
than 80 percent of study participants who read an ingredient 
declaration statement in which the vitamins A, D, E, and K were marked 
with an asterisk and accompanied with an explanatory phrase (``not a 
nutritionally significant source'') and that no longer had the phrase 
``other nutrients,'' believed that levels of vitamins A, D, E, and K 
and other nutrients would not change after eating olestra-containing 
foods.
    P&G also conducted research by a national tracking survey to 
measure consumer awareness of olestra and to determine whether 
consumers had concerns about olestra's potential GI effects (Docket No. 
00F-0792). Survey results were obtained between January 1998 (just 
prior to the start of national marketing of olestra-containing foods) 
and May 1999. P&G reported that the results of the tracking survey 
showed that population awareness of olestra-containing foods increased 
substantially during this period (from 38 percent to well over 70 
percent). The study also showed that respondents who were familiar with 
olestra-containing foods were quite concerned about possible GI 
effects. The percentage of ``aware'' consumers who were at least 
somewhat concerned about GI effects averaged 74 percent at the 
beginning of the tracking survey, and 70 percent after national 
marketing of olestra-containing food was fully underway.
    Frito-Lay also conducted new studies on consumer perceptions of the 
olestra label statement to determine whether that statement was still 
capable of influencing consumer perception, as it did in 1996 (FAP 
0A4708, exhibit 7 and August 13, 1999, Docket No. 00F-0792). Because 
the 1996 perception study was conducted shortly after FDA's approval of 
olestra but before availability of olestra in any product on the 
market, no participant in the 1996 study had eaten a product made with 
olestra. Frito-Lay therefore considers that the 1996 study showed the 
effect of the label statement on a ``naive'' population. Since the 1996 
study, Frito-Lay points to numerous significant events involving 
olestra, including the nationwide availability of Frito-Lay products 
made with olestra, the FAC meeting held by FDA in 1998, and many 
national and local news stories about olestra. The new testing of the 
label statement was conducted with the protocol used in Frito-Lay's 
1996 studies.
    Frito-Lay reported that in its 1999 study, before seeing the 
required label statement, 64 percent of respondents were uncertain 
about safety, but only 6 percent said products made with olestra were 
unsafe. After viewing the label statement, the number of respondents 
who thought olestra products were unsafe more than doubled. No one who 
originally thought olestra products were unsafe changed their opinion 
after viewing the label statement. Frito-Lay presented results showing 
that only 24 percent of study participants concluded that products made 
with olestra do not affect the levels of vitamins in the body,

[[Page 46384]]

and an approximately equal distribution of participants concluded that 
olestra did or did not affect the absorption of other nutrients.
    Frito-Lay concluded from these studies that the olestra label 
statement did influence consumer perception, much like it did in 1996. 
Frito-Lay also concluded that consumers still did not understand the 
various parts of the label statement and viewed it incorrectly as a 
warning.
    FDA reviewed the consumer perception studies of the label statement 
submitted by P&G and Frito-Lay in 1999 and found them to be similar to 
the 1996 studies in methodology and types of questions asked (Ref. 33). 
This set of studies concentrated on the GI portion of the required 
label statement and perceptions of safety about products made with 
olestra. As with the 1996 studies, the studies were limited by choice 
and wording of questions and did not include, as a control, a ``no 
information'' statement. FDA notes that it is difficult, without 
careful controls, to distinguish whether a label statement 
miscommunicates information, is ignored, or is ineffective. Another 
important limitation to this study is the lack of measurement of 
initial attitudes toward olestra. Testing of initial attitudes and 
preconceptions is needed in order to identify the direction of the 
label statement's effect (i.e., whether the consumer is more accurately 
informed or not informed).
    FDA concludes that P&G's tracking study showed that consumers 
became more aware of olestra-containing snack foods as products were 
introduced nationally, and that increasing awareness was accompanied by 
concern about possible GI effects caused by these products. However, 
FDA also concludes that the tracking survey does not establish the role 
(if any) the required label statement plays in consumers' association 
of olestra-containing foods and GI effects. It cannot be determined 
from this study whether the rise in product awareness and association 
with GI effects was due to news reports, advertisements, promotions, or 
reading the label statement.
    FDA concluded that the 1998 and 1999 studies reinforced conclusions 
from the 1996 studies and support several new conclusions. The new 
conclusions include the following scenarios: (1) Consumers became more 
concerned about the safety of olestra-containing products between 1996 
and 1998, prior to the introduction of olestra-containing food into 
national distribution; (2) consumers familiar with olestra-containing 
snack food (Olean brand name) are very likely to make an association 
between olestra and possible GI effects; and (3) consumers newly 
introduced to olestra-containing products by the introduction of Olean 
brand products into local stores and the accompanying advertising and 
promotion are just as likely to make the association between olestra 
and GI effects as those who already knew about Olean products.
    FDA notes that the 1998 study gave respondents a choice of ``I 
don't know'' about safety. Given this option, 45 to 49 percent of 
participants in the 1998 study chose the response ``I don't know'' when 
asked about safety, and only 10 to 13 percent of participants in the 
1998 study chose the response ``unsafe.'' In contrast, in the 1996 
survey, when participants did not have an option to choose ``I don't 
know'' when asked about safety, 38 to 61 percent of participants chose 
the response ``unsafe.''

G. 1998 FAC Discussion of the Label Statement

    The FAC discussed the required label statement on the last day of 
the 3-day meeting (June 17, 1998), after new data and information 
concerning possible GI and nutritional effects were presented and 
discussed. The FAC was to consider whether, in light of the new data 
and information concerning the consumption of olestra, the label of 
olestra-containing products should be changed in any way. The FAC was 
also asked to consider what factual information, if any, regarding the 
consequences of consuming olestra-containing products should be 
disclosed on the product label. FDA began the session by discussing the 
scope of the agency's authority, under the act, regarding labeling. The 
sponsor (P&G) made presentations to the FAC, followed by Frito-Lay, and 
CSPI. The FAC asked questions at the end of each presentation. 
Following this portion of the meeting, each FAC member was polled 
regarding the label statement.
    Polling the individual members of the FAC about whether the label 
statement should be changed revealed a wide variation in opinions on 
the labeling issue.\43\ A majority of members, however, did agree that 
the label statement should be modified in some way in order to make its 
messages more clear to the consumer. Several members stated that some 
labeling information about olestra was needed, based in part on their 
view that olestra-containing foods were still relatively new products 
and that consumers were not entirely familiar with these products. Some 
members of the FAC suggested there be a sunset clause on the label 
statement because after consumers became familiar with olestra, there 
would no longer be a need for a label statement.
---------------------------------------------------------------------------

    \43\ Transcript, vol. 3, pp. 101-174.
---------------------------------------------------------------------------

    Members made various suggestions for different wordings of the 
label statement to clarify to consumers the likelihood that olestra 
would cause GI effects and the nature of those effects. Other members 
expressed concern that consumers might confuse olestra's effect with 
more serious GI symptoms. Some members of the FAC concluded that 
olestra's GI effects did not warrant a special label statement, 
especially because consumers might mistakenly attribute more serious GI 
symptoms to the olestra. Other members thought a label statement should 
include information to tell the consumer to seek medical attention if 
symptoms persist. Several members said they believed that the current 
data did not support keeping the portion of the label statement on 
abdominal cramps.
    A majority of the members of the FAC specifically agreed that the 
portion of the label statement regarding ``vitamins added'' should be 
removed and replaced with an asterisk following the vitamins in the 
ingredient listing and a footnote indicating that the added vitamins 
are not a nutritionally significant source or not nutritionally 
available. Both P&G and CSPI agreed that this approach was an 
acceptable and effective way to explain that the presence of the 
vitamins in the ingredient listing is not meant to imply that these 
foods are a source of these vitamins.\44\
---------------------------------------------------------------------------

    \44\ Transcript, vol. 3, pp. 92-93.
---------------------------------------------------------------------------

    A majority of members of the FAC agreed that there is no basis, at 
this time, for adding back any carotenoid, and that the role 
carotenoids play, if any, in human health is not yet understood. 
Members did say that the sponsor and the agency should be aware of the 
evolving understanding of the health effects of carotenoids, and 
consider that information and its bearing on the use of olestra. Some 
members expressed reservations about not having any statement on the 
label about olestra's potential to interfere with the absorption of 
fat-soluble nutrients such as carotenoids, and suggested that the 
statement about ``other nutrients,'' might be clarified by changing the 
phrase to ``nutrients found in fruits and vegetables.''

IV. FDA's Conclusions

A. The Applicable Legal Standard

    Under section 409(c)(3) of the act, a food additive shall not be 
approved if

[[Page 46385]]

such approval would result in the misbranding of a food containing the 
food additive. Misbranding includes labeling that is misleading because 
it fails to reveal facts material with respect to consequences 
resulting from use of the additive under ``customary or usual'' 
conditions (sections 201(n) and 403(a)(1) of the act). Thus, the data 
and information of principal relevance to evaluating whether olestra 
must bear a label that discloses, for example, the possible GI effects 
of olestra, are those that evaluate the additive's effects when eaten 
at levels, and in patterns of consumption, that are customary or 
usual.\45\ As the preceding discussion reflects, FDA has considered all 
of the evidence in the record and has considered the preapproval 
studies in light of the postapproval investigations reflecting 
customary or usual patterns of consumption.
---------------------------------------------------------------------------

    \45\ This would be in contrast to the preapproval studies which 
were designed to assess safety.
    In addition, it is critical to recognize that the issue 
presented by this petition is not whether olestra is safe for use in 
savory snacks; that issue was addressed in the 1996 final rule. 
Instead, the question before the agency is what labeling, if any, 
must be required for foods containing olestra to ensure that they 
are not misbranded (section 403(a)(1) of the act). Accordingly, the 
act's ``reasonable certainty of no harm'' safety standard in Sec.  
170.3(i) (21 CFR 170.3(i)), does not apply here.
---------------------------------------------------------------------------

    FDA does not ordinarily require special labeling on a food that may 
have consequences of consumption (such as GI effects) when the 
available information shows that consumers are aware that such food 
cause the effects. Psyllium husk is an example of an ingredient that 
may cause GI effects. Consumers are aware of these potential effects 
because psyllium husk has been used as a laxative. However, FDA's 
health claim regulation for psyllium husk does not require a label 
disclosing these effects (Sec.  101.81). In those situations in which 
consumers understand the possible consequences of consuming a 
particular food, information describing those consequences is not new 
information for consumers and thus, such disclosure would not be 
material within the meaning of section 201(n) of the act. Thus, 
information about consumer knowledge of olestra and its potential to 
cause effects (such as GI effects) is relevant to determining whether 
labeling is required to prevent misbranding of olestra-containing food.

B. FDA's Conclusions Regarding Gastrointestinal Effects

1. Basis of the 1996 Final Rule--GI Effects
    a. Abdominal cramping. In 1996, the agency concluded that olestra 
had the potential to cause abdominal cramping. FDA's conclusion was 
based primarily on two 8-week studies designed to assess olestra's 
safety in terms of its potential nutritional effects. These 8-week 
studies maximized participants' exposure to olestra in order to 
maximize the additive's possible nutritional effects. Although FDA 
estimated an intake of 20 g/d for the ``high'' acute consumer of 
olestra (every day for 12 weeks) (61 FR 3118 at 3124), the highest dose 
used in these studies (32 g/d) well exceeded this estimate. In 
addition, in these preapproval studies, olestra was incorporated into 
savory snacks as well as a variety of foods for which it is not 
approved for use, and these foods were eaten at every meal for 56 
consecutive days. Finally, diets in these studies contained all the 
ambient levels of fat with no adjustment for the olestra added to the 
diet. As such, the 8-week studies were not designed to address the 
effects of customary consumption of olestra-containing snack foods. 
Based on the information available in 1996, the agency found that there 
were no safety concerns with the use of olestra in savory snacks.
    Although FDA determined in 1996 that the 8-week studies did not 
reflect conditions of use that are usual or customary for the 
consumption of savory snacks, there were no other data or information 
available reflecting the usual or customary use of olestra-containing 
snack foods. Thus, FDA concluded that it would be prudent to rely on 
the available data that indicated that under some circumstances olestra 
had the potential to cause abdominal cramps. Because snack foods 
containing olestra were new, the agency further concluded that 
consumers would not know to associate abdominal cramps with these 
foods. Accordingly, FDA required that products containing olestra bear 
a label statement indicating that olestra may cause abdominal cramps. 
The agency imposed the requirement for this label statement because it 
concluded that consumers were not familiar with the newly approved food 
additive, olestra, and a label statement would allow consumers to 
associate GI symptoms they might experience with olestra and preclude 
unnecessary concern about such effects (61 FR 3118 at 3161).
    b. Loose stools. In 1996, the agency also concluded that olestra 
had the potential to cause the GI effect ``loose stools.'' \46\ The 
studies on which this conclusion was based are the same studies 
discussed above on abdominal cramps, i.e., the two 8-week studies. 
These studies were designed to measure the potential nutritional 
effects from consumption of olestra-containing foods, and were not 
designed to address potential GI effects from usual or customary 
consumption of olestra-containing savory snacks. Nevertheless, in the 
absence of more specific data, FDA relied on the data from the 8-week 
studies, which the agency concluded showed that at high doses, olestra 
increased the potential for loose stools. Accordingly, FDA required a 
label statement about the potential of olestra consumption to cause 
loose stools (61 FR 3118 at 3153). FDA believed that information on the 
label would enable consumers to associate olestra with any GI effects 
and preclude any unnecessary concerns about the origin of such effects. 
FDA evaluated the data available in 1996 and concluded that a label 
statement telling consumers that olestra may cause loose stools was 
necessary so that olestra-containing food products would not be 
misbranded within the meaning of section 201(n) of the act. In 
addition, FDA required the label statement about loose stools because 
at the time of the final rule, consumers were familiar neither with 
olestra itself, nor its potential to cause GI symptoms such as loose 
stools.
---------------------------------------------------------------------------

    \46\ As noted previously, FDA concluded in 1996 that these 
effects are not adverse health effects.
---------------------------------------------------------------------------

2. Data in the Current Petition--GI Effects
    Three issues are relevant to determining whether the required 
statement concerning olestra's potential to cause loose stools and 
abdominal cramping should be modified: The additional data on olestra's 
association with these effects under customary or usual conditions of 
use; research concerning consumer understanding of this portion of the 
required label statement; and the evidence regarding the status of 
consumer knowledge of olestra and its potential to cause such 
effects.\47\
---------------------------------------------------------------------------

    \47\ The agency also reviewed data from the petitioner's Stool 
Composition Study, which address the safety of olestra (i.e., do the 
loose stools that olestra may cause constitute diarrhea that would 
be harmful from a health risk standpoint?). As noted, in 1996, FDA 
concluded that olestra was safe for use in savory snacks, 
specifically determining that loose stools caused by consumption of 
the additive were not ``harm'' within the meaning of the applicable 
safety standard (section 409(c) of the act; Sec.  170.3(i)). The 
results of the Stool Composition Study confirm that olestra does not 
cause diarrhea but simply adds bulk and softens the stool.

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

[[Page 46386]]

    a. Abdominal cramping. In 1996, when FDA required the label of 
foods containing olestra to list the GI symptom ``abdominal cramping,'' 
it did so on the basis of data generated under conditions that were not 
customary or usual for savory snack use (see section 201(n) of the 
act). Since then, FDA has received and reviewed new data and 
information designed to evaluate olestra's effects under the customary 
or usual conditions of use for savory snacks. These new data provide no 
evidence of an increased frequency of abdominal cramps due to the 
ingestion of olestra in savory snacks. This lack of association is 
consistently found in several well designed, double-blind, placebo-
controlled studies.
    Specifically, the Home Consumption Study was conducted under 
circumstances that more closely reflect the usual and customary 
conditions of use for savory snacks. As noted, in this study, there was 
no evidence of an increase in reported abdominal cramping among 
subjects who ate olestra-containing foods compared to those who ate 
triglyceride-containing foods. Importantly, the Home Consumption Study 
had sufficient power to detect differences in the frequency of reported 
GI effects between the olestra and the triglyceride consuming groups, 
but such an effect was not found for abdominal cramping. Likewise, 
results from the Acute Consumption Study showed no difference in the 
rate or severity of abdominal cramps for the group consuming olestra 
compared to the group consuming triglyceride. Although CSPI has raised 
questions about the power of the Acute Consumption Study, the agency 
believes that the results of that study provide meaningful information 
that corroborates the findings of the more powerful Home Consumption 
Study. In addition, these results are confirmed by the Rechallenge 
Study. That investigation used a population of consumers who had 
previously reported a GI effect that they associated with eating an 
olestra-containing snack; in their initial symptom episode, the 
majority claimed to have experienced abdominal cramps. As noted 
previously, in the Rechallenge Study, there was no difference in the 
frequency of reports of abdominal cramps after eating olestra-
containing chips when compared to triglyceride-containing chips. 
Finally, the results of the Stool Composition Study are consistent with 
outcomes of the foregoing three studies. In this study, although there 
was an increase in the percentage of symptom days for abdominal 
cramping, with increasing olestra dose, the difference was not 
significant. Accordingly, FDA concludes that consumers of olestra are 
no more likely to report abdominal cramping than are consumers of 
triglyceride chips under normal use conditions.\48\
---------------------------------------------------------------------------

    \48\ FDA reviewed a number of reports from passive surveillance 
of olestra consumers. As noted in the previous discussion, passive 
surveillance cannot establish cause and effect, although such 
information may be useful in supporting hypothesis generation. FDA 
has not relied upon information from the passive surveillance in 
reaching its conclusions about the current label statement.
---------------------------------------------------------------------------

    FDA has also evaluated information about whether the current 
olestra label statement communicates effectively to consumers (see 
section III.F of this document). In general, evidence from consumer 
perception studies shows that after reading the required label 
statement, a majority of consumer participants did not correctly 
understand the nature, severity, or frequency of possible GI effects as 
a result of consumption of an olestra-containing snack. Although FDA's 
purpose in requiring the label was to provide information to consumers, 
most of those surveyed viewed the label statement as a warning and thus 
drew inaccurate conclusions about olestra's safety. Accordingly, FDA 
concludes that the required label statement is not an effective means 
of communicating accurate information to olestra consumers.
    The new data and information that the agency has received since the 
1996 final rule provide no evidence of an increased frequency of 
abdominal cramps when olestra-containing foods are consumed under the 
customary or usual conditions of use for savory snacks (see section 
201(n) of the act). As discussed previously, this lack of association 
is consistently found in several well designed, double-blind, placebo-
controlled studies. Accordingly, FDA finds that there is no scientific 
basis to support a statement on the label of foods containing olestra 
that olestra consumption may cause ``abdominal cramping.''
    b. Loose stools. As noted, prior to the approval of the use of 
olestra for savory snacks and their subsequent marketing, consumers had 
little knowledge of, and no experience with, olestra. Since the 1996 
decision, the agency has received additional data about olestra and the 
nature and frequency of loose stools; these new data better reflect the 
conditions of use that are customary or usual for savory snacks. FDA 
has found that olestra may increase the frequency of loose stools and 
bowel movements but that the magnitude of the increase is minor and the 
severity and impact of these effects on daily activity are not 
different from other foods that may cause an effect such as loose 
stools. In addition, the record before the agency shows that consumers 
are now familiar with olestra's potential to cause loose stools.
    In particular, the Home Consumption Study found that consumers of 
olestra-containing chips experienced a small but measurable increase in 
more frequent bowel movements and loose stools compared to those who 
ate triglyceride-containing chips. Because of the number of subjects 
enrolled (3,181), and the length of time for the study (42 days), the 
study was able to detect small differences in the frequency of 
symptoms. Importantly, the absolute incidence of these reports was low, 
especially relative to the background rate of reported symptoms. 
Analysis of the reported incidence of severity did not show any 
difference between the olestra and triglyceride groups. The study 
showed no increase in the use of medications or physician visits 
associated with olestra consumption. FDA's analysis of the study showed 
that consumers who reported a GI event moderated their consumption of 
chips. Assessments by participants of a symptom's effect on the ability 
to carry out normal activities showed little if any impact on the daily 
life of subjects. There was no increase in the percentages of reported 
severe impairment in performing daily activities in the olestra group 
compared to the control group. There was no evidence that these effects 
(loose stools, more frequent bowel movements) were more severe or had 
any different impact on consumers' daily activities than those 
associated with similar foods made with fat.
    Results from the Acute Consumption Study and the Rechallenge Study 
are consistent with the results from the Home Consumption Study. 
Specifically, the Rechallenge Study showed that under the conditions of 
the study, the incidence of reports of diarrhea or loose stools after 
exposure to olestra or to triglyceride chips did not differ. The 
incidence of diarrhea was 6 percent for the olestra group, 8 percent 
for the triglyceride group; the incidence of reports of loose stools 
was 5 percent for the olestra group, 7 percent for the triglyceride 
group. Subjects who had previously reported a GI effect (including 
loose stools and abdominal cramps) after consuming olestra were no more 
likely to report GI symptoms after eating olestra chips than those 
eating

[[Page 46387]]

triglyceride chips. Similarly, the Acute Consumption Study showed no 
difference in the frequency, nature, or severity of GI complaints 
(including loose stools) between the placebo (triglyceride) and olestra 
groups after a single, ad libitum eating occasion.
    At the time olestra was initially approved and first marketed, 
consumers had limited awareness of olestra and its potential to cause 
GI effects. In contrast, evidence gathered in the postapproval consumer 
perception studies and the tracking survey show that there is currently 
a high degree of awareness among the public about olestra, including a 
high degree of awareness of olestra's potential to cause GI effects. 
Results from a postapproval tracking survey show that consumers became 
more aware of olestra as products were introduced nationally.
    FDA does not have evidence to draw conclusions about the role 
played by the label statement in creating consumer awareness about 
olestra's potential to cause GI symptoms. However, as with other 
products that may cause GI effects but are not so labeled, awareness of 
the potential to cause GI effects is maintained in the population based 
on common knowledge and consumer experience. Consumers are accustomed 
to regulating their diets based on this knowledge and experience. FDA 
has no reason to conclude that the case for olestra-containing foods 
would be different.
    As previously noted, FDA has evaluated consumer perception studies 
conducted with the olestra label statement and has concluded that while 
FDA's purpose in requiring the label was to provide information to 
consumers, a significant number of consumers perceive the label 
statement as a warning about possible health consequences of olestra 
consumption and consider olestra-containing foods to be unsafe.\49\ 
This is contrary to FDA's determination that olestra is safe for use in 
savory snacks. Thus, the agency believes that the current label does 
not accurately communicate information to consumers about olestra's 
potential to cause loose stools.
---------------------------------------------------------------------------

    \49\ In fact, these studies show that many consumers attribute 
certain serious GI effects to olestra, even though there is no 
evidence of olestra's potential to cause such effects.
---------------------------------------------------------------------------

    Since the 1996 final rule, additional data about olestra and the 
nature and frequency of loose stools have become available. This 
information does not supersede the previous information, but rather, 
extends FDA's understanding of olestra under customary conditions of 
use and its potential to cause loose stools. FDA has found that olestra 
may increase the frequency of loose stools but the frequency of the 
increase is minor. FDA also has found that the severity and impact of 
this effect on daily activity are not different from other foods that 
may cause an effect such as loose stools.
    In addition, the administrative record before the agency shows that 
consumers are now familiar with olestra's potential to cause loose 
stools. FDA believes that because there is currently an awareness among 
consumers about possible GI effects of olestra, and because the 
potential effects from customary or usual consumption of olestra-
containing snacks are relatively insignificant, a label statement 
concerning loose stools for olestra-containing savory snacks is no 
longer needed to ensure that the product is not misbranded (sections 
201(n) and 403(a)(1) of the act).

C. FDA's Conclusions Regarding Nutritional Effects

1. Basis of the 1996 Final Rule--Nutritional Effects
    At the time of the 1996 final rule, FDA found that because olestra 
is a fat-like material that is not digested or absorbed, it may 
interfere with the absorption of fat-soluble components of the diet, 
including the fat-soluble vitamins A, D, E, and K. The agency had 
evaluated studies performed in humans and animals (61 FR 3118 at 3132-
3252), and considered the available information concerning nutritional 
requirements for various fat-soluble components of the diet. FDA 
concluded that the addition of vitamins A, D, E, and K (Sec.  
172.867(d)), to foods containing olestra would compensate for any 
inhibition of absorption of fat-soluble nutrients by olestra. The 
amount of vitamins added was intended to have no net effect (neither 
increase nor decrease) on vitamin status of olestra consumers. The 
agency required that the level of added vitamins be adequate to 
compensate for olestra's effects on absorption even if the olestra and 
fat-soluble vitamin are present in the gut simultaneously. 
Additionally, the agency set the amount of vitamins so that if there is 
no fat-soluble vitamin present in the gut with olestra, the level of 
added vitamin would not pose any safety concerns.
    The added vitamins A, D, E, and K are required to be declared in 
the ingredient listing (section 403(i)of the act). In 1996, FDA 
concluded that this mandatory listing of vitamins A, D, E, and K could 
mislead consumers by implying that the food would provide significant 
amounts of these vitamins (61 FR 3118 at 3161). Thus, FDA required a 
label statement to explain why these vitamins were added and why the 
food should not be considered fortified, so that olestra-containing 
food would not be misbranded (sections 201(n) and 403(a)(1) of the 
act).
    FDA required that the label include the statement ``Olestra 
inhibits the absorption of some vitamins and other nutrients. Vitamins 
A, D, E, and K have been added.'' FDA did not require a specific 
statement about carotenoids or any other fat-soluble components of the 
diet because such a statement could have falsely implied that their 
decreased absorption was known to be of significance.
2. Data in the Current Petition--Nutritional Effects
    Three issues are relevant to determining whether the required 
statement as to olestra's effects on nutrient absorption should be 
modified: The additional data on absorption of the added vitamins A, D, 
E, and K obtained since the 1996 final rule; the current understanding 
of the nutritional importance of carotenoids and olestra's effect on 
their absorption; and the research evaluating consumer understanding of 
this portion of the required label statement.
    As to the added vitamins A, D, E, and K, early data from the Active 
Surveillance Study confirm that, as the agency intended, there is no 
dietarily significant net loss or gain of vitamins A, D, E, and K due 
to the consumption of olestra-containing foods.\50\
---------------------------------------------------------------------------

    \50\ There was some indication from the Active Surveillance 
Study cross-sectional data of a small increase in vitamin K levels 
in the highest olestra consumers.
---------------------------------------------------------------------------

    The early data from the Active Surveillance Study also provide 
important information regarding olestra and carotenoids. First, these 
data show that consumption levels of olestra-containing foods are below 
FDA's original estimates and further, that co-consumption of any savory 
snack with a carotenoid-containing food is relatively rare. Second, 
although there are changes in serum measures of certain carotenoids, 
these changes are unlikely to be the result of consumption of olestra-
containing foods because the clinical cohort data reflect no 
association between the amount of olestra consumed and the changes in 
serum levels of carotenoids.
    As noted, FDA has considered the recent scientific literature 
pertaining to carotenoids and human health and concluded that the 
decreased risk of cancer is associated with increased

[[Page 46388]]

consumption of fruit and vegetables generally and that at the present 
time no specific role of carotenoids (other than the provitamin A 
function) has been identified.\51\ The agency's conclusions are 
consistent with the recent NAS report (Ref. 27) that determined that 
there is no basis at present for setting dietary requirements for any 
carotenoid. Similarly, this conclusion is consistent with the results 
of recent intervention studies, which show no benefit from treatment 
with carotenoids over control.\52,\ \53\
---------------------------------------------------------------------------

    \51\ The FAC reached the same conclusion in June 1998.
    \52\ This is true with respect to the NIH/NEI AREDS study, which 
showed no specific vitamin or carotenoid was protective of macular 
degeneration.
    \53\ Indeed, in at least one subpopulation (smokers), treatment 
with carotenoids was associated with an increased risk.
---------------------------------------------------------------------------

    FDA acknowledges that research is continuing and that the 
scientific community's understanding of the role of carotenoids in 
human health may evolve as new data emerge. The agency will review new 
information about the role of carotenoids in human health relevant to 
olestra use in savory snacks, and if necessary, take appropriate 
action. At this time, however, FDA concludes that no direct evidence 
demonstrates that the association between the consumption of diets high 
in fruits and vegetables and a decreased risk of cancer is due to any 
single carotenoid or group of carotenoids. Accordingly, FDA has 
determined that there continues to be no basis to require any label 
statement about olestra's effects on carotenoids or any other fat-
soluble nutrient.
    As discussed previously, FDA has also evaluated information about 
the effectiveness of the current olestra label statement to communicate 
about olestra's potential nutritional effects to consumers. In general, 
the evidence from consumer perception studies shows that after reading 
the required label statement, a majority of consumer participants did 
not correctly understand olestra's effect on the absorption of fat-
soluble nutrients or why vitamins A, D, E, and K would be added to 
olestra-containing foods. Accordingly, FDA concludes that the required 
label statement is not an effective means of communicating to olestra 
consumers.
    Although the currently required label statement may be 
misinterpreted by consumers, FDA still believes that because the 
presence of the added vitamins must be disclosed as ingredients of 
olestra-containing foods (Sec.  101.4(a)(1)), consumers may be misled 
and believe that such snacks are fortified with the added vitamins. 
Therefore, in order for olestra-containing foods not to be misbranded, 
the agency has determined that a statement about the presence of 
vitamins A, D, E, and K should be required. Accordingly, this final 
rule requires that the label of foods containing olestra use an 
asterisk following each of the added vitamins in the ingredient 
statement which would refer to a statement, ``Dietarily 
insignificant.'' Such a statement directly addresses the presence of 
the vitamins in the ingredient statement and closely links the message 
to the particular vitamin affected.\54\ This format and configuration 
are familiar to consumers because such a configuration has been used 
previously in the nutrition facts panel. Likewise, as noted, the 
required wording, ``dietarily insignificant,'' is similar to wording 
used in other label statements, and thus, is familiar to consumers 
(Sec. Sec.  101.60(c)(1)(ii), 101.61(b)(1)(ii), and 101.62(b)(1)(ii)).
---------------------------------------------------------------------------

    \54\ This asterisk format is supported by P&G, CSPI, and a 
majority of the FAC members present at the 1998 FAC meeting.
---------------------------------------------------------------------------

    FDA further concludes that there is no need for a contextual 
statement about olestra's effect on the absorption of the vitamins in 
order to avoid misbranding of olestra-containing foods. Indeed, 
information from consumer perception studies shows that the 1996 
required label's contextual statement about ``some vitamins and other 
nutrients'' actually tends to mislead consumers and that contextual 
information is not necessary to understand that olestra-containing 
foods do not contribute significant amounts of vitamins A, D, E, and K 
to the diet. In addition, although olestra may affect the absorption of 
other fat-soluble components of the diet, such as carotenoids, there is 
no known basis for adding back carotenoids or nutrients other than 
vitamins A, D, E, and K to olestra-containing food. Finally, there is 
no representation made on the label about ``other nutrients'' that 
would require a specific statement about such nutrients. For these 
reasons, this final rule eliminates the requirement that the label for 
foods containing olestra include the sentence ``Olestra inhibits the 
absorption of some vitamins and other nutrients.''
    In sum, having considered all of the evidence of record, FDA has 
determined that the olestra regulation, Sec.  172.867, should be 
revised to require that vitamins A, D, E, and K listed in the 
ingredient statement be labeled with an asterisk (appearing as a 
superscript) following the listing of each of these vitamins, and that 
the asterisk reference the phrase, ``Dietarily insignificant,'' which 
shall appear immediately following the ingredient statement.

V. Response to Comments on the Label

    In this section, FDA responds to comments not previously addressed 
in this document. FDA considered these comments and responds in this 
section of the document.

A. Label Statement for GI Effects

    (Comment 10) In comments to both the 1996 final rule and the 
current petition, Frito-Lay recommended that the statement about the GI 
effects of olestra be eliminated. Frito-Lay based its recommendation on 
the results of studies, such as the petitioner's postapproval studies, 
showing that consumption of snack foods made with olestra produces no 
meaningful GI effects. Frito-Lay also cited a consumer perception study 
suggesting that consumers may attribute GI effects to olestra when 
their symptoms are caused by a more serious condition requiring medical 
attention. In that study, 58 percent of consumers said they would delay 
medical attention if GI changes occurred after eating products bearing 
the olestra label statement. A comment from P&G to the 1996 final rule 
argued that the label statement is inconsistent with data from the 
postapproval studies and has the potential to mislead consumers. P&G 
objected to the suggestion at the 1998 meeting of the FAC that the GI 
effects statement be amended and subject to a sunset clause, rather 
than dropped entirely, by arguing that discontinuing the GI effects 
portion of the label statement would be more consistent with the 
existing data and prevailing legal precedent.
    In contrast, several comments to the 1996 final rule specifically 
stated that a GI effects statement was warranted but provided no 
factual evidence or rationale for their recommendation.
    FDA agrees that the requirement for a label statement about 
olestra's potential to cause GI effects should be eliminated. As noted 
previously, P&G's postapproval studies show that customary or usual 
consumption of olestra in savory snacks causes only minor GI effects, 
and that the public is now aware of olestra's potential to cause GI 
effects. Therefore, the agency has no basis to require a label 
statement regarding olestra's potential to cause GI effects.
    (Comment 11) A comment from CSPI to the current petition stated 
that instead of eliminating the label statement about GI effects, the 
statement should be amended to indicate that GI effects may occur in a 
``small percentage

[[Page 46389]]

of consumers.'' CSPI asserted that consumers need information on GI 
effects so that they can learn to associate olestra with possible 
symptoms and can avoid olestra in the future if such symptoms occur. 
CSPI also asserted that olestra's GI effects are material consequences 
that may result from customary consumption and that the label statement 
would be misleading without a statement about GI effects. CSPI asserts 
that P&G's two 8-week studies, together with a clinical study published 
in the British Journal of Nutrition \55\ (Ref. 34), show an association 
between consumption of olestra (in the case of P&G) or sucrose 
polyester (in the case of the study published in the British Journal of 
Nutrition) and GI symptoms. CSPI also stated that the postmarketing 
studies provide some reassurance that no more than a small percentage 
of consumers experience GI symptoms.
---------------------------------------------------------------------------

    \55\ FDA notes that this study was a double-blind, placebo-
controlled, randomized, cross-over trial in which subjects consumed 
20 to 40 g sucrose polyester or triacylglycerol per day. Each 
treatment was administered for three months. The study included 
measurements of the effect of each treatment on GI symptoms and 
plasma carotenoid concentrations. The article does not state whether 
the sucrose polyester used meets the specifications for olestra. 
Sucrose polyester was incorporated into chips, beefburgers, meat 
pies, sausages, sausage rolls, fruit pies, milk, margarine, salad 
cream, fruit dessert, processed cheese, biscuits, peanut butter, 
cake, crisps, chocolate spread, and chocolate bars.
---------------------------------------------------------------------------

    FDA does not agree that olestra-containing foods should be required 
to bear a label statement indicating that GI effects may occur in a 
small percentage of consumers. The standard for determining whether 
this information must be required on the label is whether the labeling 
fails to reveal facts that are material with respect to consequences 
which may result under the conditions of use prescribed in labeling or 
advertising or under such conditions that are customary or usual 
(section 201(n) of the act). The fact that olestra-containing foods can 
cause GI effects under conditions such as those in P&G's two 8-week 
studies and the study published in the British Journal of Nutrition 
must be considered in light of the data from studies addressing the GI 
effects associated with customary or usual olestra consumption. As with 
other foods, GI symptoms may occur in a small percentage of olestra 
consumers, but the available data show that customary or usual 
consumption of olestra-containing foods does not cause GI symptoms with 
a frequency, severity, or impact on daily activity that are different 
from those from triglyceride snacks. In addition, the agency has 
determined that consumer perception studies and tracking surveys show 
that there is a high degree of public awareness concerning olestra and 
its potential effects. Based on the minor GI effects associated with 
customary or usual consumption of olestra-containing foods and the 
public's awareness of the potential for olestra to cause GI symptoms, 
the agency has concluded that olestra-containing foods should not be 
required to bear a label statement informing consumers of possible GI 
symptoms resulting from olestra consumption.
    (Comment 12) Several comments to the current petition stated that 
the wording of the GI effects statement should be changed to indicate 
that symptoms may be ``severe.'' Many of these comments were from 
consumers who reported having GI effects that they attributed to 
olestra. Another comment supported the suggested change by citing 
consumers' GI effects reported to CSPI.
    Comments from CSPI, individual consumers, and manufacturers of 
baked, fat-free snacks to the 1996 final rule stated that the wording 
of the GI effects statement should be changed to describe a greater 
number of potential side effects \56\ and to indicate that the side 
effects could be ``severe.'' Several comments also suggested that the 
label statement should indicate that symptoms occur ``commonly.'' Some 
comments cited reports submitted to CSPI and P&G that report severe GI 
effects after olestra consumption as the rationale for the suggested 
labeling. CSPI asserted that if all pertinent symptoms are not 
identified, consumers might continue to eat olestra-containing foods 
even when GI disturbances are occurring, because many consumers will 
not make the connection between consumption of the fat substitute and 
symptoms not specified on the label statement. CSPI reported the 
results of a telephone survey that showed that 7.4 percent of consumers 
experienced GI effects or headache after an average of 4.8 exposures to 
olestra over a 2-month period. CSPI also stated that P&G's two 8-week 
studies showed that half of the subjects experienced diarrhea or other 
symptoms during the study. The comment also reported data from a study 
conducted by Frito-Lay that showed a 9 percent increase in anal oil 
leakage associated with olestra consumption.\57\ CSPI compared the 
labeling for adverse effects caused by drugs to the labeling of olestra 
related effects, and argued that because olestra is consumed more 
widely, at greater amounts, and over longer periods of time than drugs, 
labeling for effects should be more complete and explicit.
---------------------------------------------------------------------------

    \56\ In its comments, CSPI suggested that symptoms such as 
diarrhea, loose stools, increased bowel movements, fecal urgency, 
nausea, gas, cramps, bloating, anal leakage, yellow-orange underwear 
staining, greasy bowel movements, yellow-orange discoloration of 
stools, and oil in toilet appear on the label statement.
    \57\ FDA believes that CSPI is referring to a marketing study 
conducted by Frito-Lay. Frito-Lay informed FDA that the execution of 
the study was flawed. FDA relied on data from the petitioner's 
safety studies to address the issue of anal oil leakage (61 FR 3118 
at 3154-3155).
---------------------------------------------------------------------------

    In contrast, a comment to the 1996 final rule from P&G opposed a GI 
effects statement listing all GI symptoms that may possibly occur 
following olestra consumption. The comment stated that the clinical 
data show that the digestive effects of olestra are similar to the 
effects that consumers experience from eating certain other foods and 
food products (such as products that contain psyllium or wheat fiber) 
that are not specially labeled. The comment also stated that olestra's 
effects are similar to those of other foods that have no impact on 
daily activities and are not specially labeled.
    FDA does not agree that olestra-related GI symptoms should be 
labeled as ``severe.'' FDA has no basis for concluding that the GI 
symptoms caused by olestra are severe when olestra-containing snacks 
are consumed under customary or usual conditions. Moreover, these 
comments provide no evidence that any severe symptoms were actually 
caused by olestra. As noted earlier (section III.B of this document), 
the reports of the type cited in the comments cannot be used to draw 
conclusions about cause and effect. Furthermore, the Home Consumption 
Study and the Acute Consumption Study demonstrate that the GI symptoms 
caused by customary or usual olestra consumption are not severe. In 
fact, the petitioner's postapproval studies show that customary or 
usual consumption of olestra in savory snacks causes only a minor 
increase in the frequency of loose stools.
    FDA does not agree that the wording of the label statement should 
disclose a greater number of potential side effects. As described 
above, the postapproval studies show customary or usual consumption of 
olestra-containing foods causes only a minor increase in the frequency 
of loose stools and bowel movements, and no increase in the frequency 
of abdominal cramps. The results of the studies do not provide evidence 
that there are other GI symptoms resulting from customary or usual 
consumption of olestra-containing foods that warrant special labeling.

[[Page 46390]]

Based on the results of the postapproval studies, reviewed in light of 
the preapproval investigations, FDA has determined that there is no 
longer a basis to require special labeling for loose stools, abdominal 
cramps, or any other GI symptom.
    (Comment 13) P&G stated in a comment to the 1996 petition that the 
GI effects statement is inconsistent with FDA's handling of psyllium-
containing foods. The comment stated that the digestive effects that 
occur after eating psyllium-containing foods at levels necessary to 
support the agency's health claim are the same as for olestra, softer 
fecal contents and more frequent bowel movements, but are likely more 
pronounced than those that occur after eating olestra-containing foods. 
The comment stated that no label information related to GI effects is 
required on psyllium-containing foods.
    As explained previously, FDA has concluded that olestra-containing 
foods should no longer be required to bear a statement about olestra's 
potential to cause GI effects. Therefore, whether the GI effects 
statement originally required in the olestra label is inconsistent with 
the labeling of psyllium husk-containing foods is no longer an issue.
    (Comment 14) A comment from CSPI to the current petition objected 
to P&G's argument that the required labeling of olestra-containing 
foods is not consistent with the labeling of GI effects from psyllium-
containing foods. CSPI argued that the GI effects of psyllium and 
olestra are different by citing FDA's published statements that 
psyllium would have no effect on the bowel other than to promote normal 
function by softening fecal contents and increasing fecal volume (63 FR 
8103 at 8115, February 18, 1998) while olestra may cause bloating, 
loose stools, abdominal cramps, and diarrhea-like symptoms (61 FR 3118 
at 3159). CSPI also states that psyllium's mild GI effects would not 
cause consumers significant discomfort, undue concern, or cause them to 
seek unnecessary medical treatment. CSPI points out that FDA does 
require disclosure of the material effects of psyllium consumption, the 
potential for esophageal blockage from not consuming adequate amounts 
of fluids. CSPI concludes that the requirement for disclosure of 
psyllium's material effects, the potential to cause choking, and the 
fact that disclosure of psyllium's nonmaterial mild bowel-normalizing 
effects, are not required to be disclosed is consistent with requiring 
disclosure of the material GI and carotenoid effects of olestra.
    FDA determines the need for special labeling on a case-by-case 
basis. In this case, FDA must consider not only whether the potential 
GI effects of olestra-containing foods rise to the level that warrant 
special labeling, but also whether consumers are aware of the potential 
GI effects associated with the consumption of olestra-containing foods. 
Customary or usual consumption of psyllium husk-containing foods may 
cause stool softening effects and increases in stool volume and 
frequency of bowel movements (63 FR 8103 at 8115). Products containing 
psyllium husk are not specially labeled for GI effects because FDA 
believes consumers are aware that psyllium husk is dietary fiber and 
consumers know the effects of dietary fiber. Therefore, the labels of 
psyllium husk-containing foods are not required to disclose the stool 
softening effects and increases in stool volume and frequency of bowel 
movements associated with customary or usual consumption of foods 
containing psyllium husk. Based upon data and information obtained 
since the 1996 final rule, FDA believes that the GI effects of 
customary or usual consumption of olestra-containing foods are not 
significantly different from the stool softening effects and increases 
in stool volume and frequency of bowel movements associated with the 
customary or usual consumption of psyllium husk-containing foods.\58\ 
In addition, FDA believes that there is now a high degree of awareness 
concerning olestra and its potential to cause GI effects. Based on the 
nature of the GI effects caused by olestra-containing foods and the 
public's awareness of such effects, the agency does not believe that 
olestra's potential to cause GI effects warrants special labeling.
---------------------------------------------------------------------------

    \58\ The published statement about olestra's GI effects 
referenced in the comment by CSPI represents effects seen under the 
consumption conditions associated with the petitioner's preapproval 
studies that were designed to demonstrate the safety of olestra.
---------------------------------------------------------------------------

    (Comment 15) A comment from CSPI to the current petition stated 
that the olestra label statement should advise consumers to contact a 
health professional if GI symptoms persist because such symptoms may 
represent a problem more serious than those associated with the 
consumption of olestra-containing foods.
    FDA disagrees with this comment. While FDA agrees that consumers 
experiencing persistent GI symptoms should contact a health 
professional because such symptoms may represent a condition more 
serious than those caused by olestra, a food label is not the proper 
place to provide medical advice unrelated to the product (61 FR 3118 at 
3162). FDA notes, however, that the decision to delete the label 
statement requirement is consistent with the expressed concern that 
consumers may erroneously conclude that GI symptoms are related to 
olestra when, in fact, they are caused by something else.
    (Comment 16) Assuming that the label statement would be retained, 
comments from P&G, Frito-Lay, academia, and several trade associations 
to the 1996 final rule stated that the wording of the GI effects 
statement should be changed to indicate that olestra causes a 
``laxative effect.'' Comments cited focus group studies showing that 
the current statement creates unwarranted alarm and implies that the 
product is harmful. A comment from P&G reported research demonstrating 
that the phrase ``laxative effect'' was able to communicate the idea of 
loose stools and was more effective in communicating the range of other 
possible symptoms than the phrase ``loose stools.'' This comment also 
stated that the suggested changes are consistent with the views 
expressed by the FAC at its 1995 meeting. Other comments supported use 
of the term ``laxative effect'' by arguing that the current label 
statement is not consistent with the precedent set by the labeling of 
other food additives that cause similar effects, such as mannitol, 
sorbitol, and polydextrose.
    In contrast, one comment opposed use of the term ``laxative 
effect'' because it puts olestra in the category of psyllium, and 
expressed the opinion that olestra does not belong in the same category 
as psyllium but provided no rationale for the opinion expressed. A 
comment from CSPI opposed a label statement indicating that olestra is 
similar to fiber because such a label statement would confuse the 
public. The comment asserted that although fiber and olestra cause 
similar GI symptoms, the appearance and disappearance of symptoms are 
so different that the label statement would be ``highly deceptive.''
    FDA does not agree that olestra-containing foods should be required 
to bear a label statement indicating that olestra causes a ``laxative 
effect.'' Use of the term ``laxative effect'' in a label statement was 
discussed in the 1996 final rule. The agency chose not to use the term 
``laxative effect'' in the label statement because such use may imply 
the therapeutic use of olestra as a laxative (61 FR 3118 at 3162). 
These comments provide no basis for the agency to change its position 
on this matter. Moreover, given the results of the postapproval 
studies, FDA believes that there is no longer a basis for requiring 
special labeling about the potential GI effects associated with 
customary or usual consumption of

[[Page 46391]]

olestra-containing foods. Therefore, the specific characterization of 
these GI effects by terms such as ``laxative effect'' is no longer an 
issue.
    (Comment 17) A comment from CSPI to the 1996 final rule stated that 
olestra causes diarrhea and the word ``diarrhea'' should appear in the 
label statement. CSPI stated that olestra-related diarrhea meets the 
criteria established for ``clinical diarrhea'' discussed at the 1995 
meetings of the Olestra Working Group (OWG) \59\ and FAC. In support of 
its comment, CSPI quotes portions of the FDA memorandum that discusses 
data from the preapproval Fecal Parameters Study (Ref. 22). CSPI quotes 
portions of the memo discussing subjects' ability to distinguish 
between ``normal,'' ``loose,'' and ``diarrhea'' stool as well as 
portions of the memorandum discussing water loss through diarrheal and 
nondiarrheal stools. CSPI states that one of the criteria for 
``clinical diarrhea'' discussed at the 1995 meeting of the OWG and FAC 
was increased water content of diarrheal stool compared to normal or 
loose stool. CSPI also asserted that in the petitioner's preapproval 
Oil Loss Study, bowel movements exceeded 3/d for subjects in all the 
study groups who consumed olestra potato chips while no such increase 
was reported for subjects who consumed chips with triglyceride. CSPI 
also reports that some subjects in the preapproval study of patients 
with inflammatory bowel disease reported an increased frequency of 
bowel movements. CSPI states that bowel movement frequency exceeding 
three per day was a criteria for ``clinical diarrhea'' considered at 
the 1995 meetings of the OWG and FAC. CSPI also quotes an FDA 
memorandum that reviews a preapproval study of the effect of olestra on 
intestinal micro flora (Ref. 35). CSPI quotes a portion of the 
memorandum stating that the projected means for fecal volume for the 
olestra-fiber consuming groups \60\ in the study indicate diarrhea at 
24 g of olestra if the strict definition of diarrhea used by research 
gastroenterologists (200 g/d) is applied.
---------------------------------------------------------------------------

    \59\ The OWG was a subcommittee of the 1995 FAC functioning as a 
special working group on olestra. The OWG was made up of several 
members of the FAC as well as consultants and indepth review experts 
who represented scientific disciplines appropriate for the 
evaluation of a macro-ingredient fat substitute. The OWG met for 3 
days (November 14-16, 1995) and reported its findings to the FAC in 
a meeting on November 17, 1995. The transcripts for the 1995 FAC 
meetings are available at the Division of Dockets Management (see 
ADDRESSES).
    \60\ FDA notes that subjects in the study were fed breakfast 
meals daily containing 7 g or 24 g of fiber with 24 g of either 
olestra or triglyceride for 28 days.
---------------------------------------------------------------------------

    FDA does not agree that olestra-containing foods should be required 
to bear a label statement indicating that olestra causes diarrhea. FDA 
considered the evidence presented by CSPI during the agency's review of 
the original petition for the use of olestra in savory snacks. Upon 
evaluation of all of the data considered in the original petition, FDA 
concluded that the ``diarrhea'' reported by study subjects was not 
diarrhea in the medical sense because it was not associated with 
objective measures of diarrhea (i.e., the loss of water or 
electrolytes) (61 FR 3118 at 3159). Moreover, as discussed previously, 
data from the petitioner's Stool Composition Study support FDA's 1996 
decision that consumption of olestra does not cause medical diarrhea. 
Therefore, FDA has no basis to require a label statement indicating 
that olestra causes diarrhea.
    (Comment 18) A comment from CSPI to the 1996 final rule stated the 
group's opposition to any use of the phrase ``excessive consumption of 
olestra'' in the label statement because P&G's data show that 
consumption of even modest amounts of olestra can cause GI 
disturbances. CSPI also opposed labeling indicating that olestra's GI 
symptoms were ``usually minor,'' arguing that diarrhea is not a minor 
symptom and that some subjects experienced moderate or severe symptoms.
    At the time of the 1996 final rule, FDA believed that it was 
prudent to rely on the data generated from the safety studies as a 
basis for requiring labeling to disclose potential GI effects of 
olestra-containing foods. The data generated from the safety studies 
did not provide a basis to characterize the frequency of GI symptoms or 
the consumption levels at which consumers would experience such effects 
under customary or usual consumption of savory snacks. Data and 
information obtained since the 1996 final rule examining the effect of 
customary or usual consumption of olestra-containing foods show that 
olestra causes only minor increases in the frequency of loose stools 
and bowel movements, and no increase in the frequency of abdominal 
cramps. Based on these findings, the agency believes that there is no 
longer a basis to require a label statement about the possible GI 
effects associated with the consumption of olestra-containing foods. 
Therefore, use of specific phrases such as ``excessive consumption of 
olestra'' and ``usually minor'' in the label statement are no longer at 
issue.

B. Label Statement for Nutritional Effects

    (Comment 19) Comments from CSPI and Frito-Lay to the current 
petition suggested that the label statement regarding the addition of 
vitamins A, D, E, and K should be replaced with an asterisk and a 
phrase such as ``Not nutritionally significant'' because the current 
statement is confusing. Frito-Lay stated that the suggested labeling 
will ensure that consumers know the product has not been fortified to 
provide a nutritional benefit with respect to vitamins A, D, E, and K. 
Frito-Lay also stated that the vitamin statements should be eliminated 
from the olestra label because they are widely misunderstood and P&G's 
postapproval research shows that the added vitamins compensate for any 
absorptive effect of olestra.
    Similarly, comments from P&G, Frito-Lay, trade associations, and 
academia to the 1996 final rule stated that the statements regarding 
added vitamins should be dropped from the label. Some of these comments 
asserted that the added vitamins should be labeled instead in the 
ingredient list with an asterisk directing consumers to a statement 
such as ``Not a nutritionally significant source.'' Arguments presented 
in support of this recommendation were summarized briefly as follows: 
(1) Consumer studies submitted by P&G and Frito-Lay arguably show that 
the current label statement is difficult for consumers to understand; 
(2) quantitative research submitted by P&G shows that the suggested 
labeling (use of an asterisk and referencing language such as ``Not a 
nutritionally significant source'') best communicates the fact that 
olestra will have no net effect on the status of vitamins A, D, E, and 
K; (3) the suggested label statement is consistent with the views 
expressed by the FAC at the 1995 and 1998 meetings; and (4) consumers 
are accustomed to seeing the suggested-type of labeling on the 
nutrition label for skim milk and some fat-free products; therefore, 
they are more likely to understand it.
    FDA agrees with these comments. As discussed previously, by this 
final rule, a label statement that explains olestra's potential effects 
on the absorption of fat-soluble vitamins and other nutrients is no 
longer required, and information that informs consumers that olestra-
containing foods have not been fortified with vitamins A, D, E, and K 
will be provided through an asterisk and the statement ``Dietarily 
insignificant'' that will follow the ingredient list of olestra-
containing foods.

[[Page 46392]]

    (Comment 20) Some comments to the 1996 final rule suggested 
specific language changes to the vitamin statements because the 
statements in the label are too vague or misunderstood by consumers. 
All of the suggested language changes indicated that olestra interfered 
with the absorption of vitamins A, D, E, and K and that these vitamins 
were added to compensate for potential losses.\61\ A comment from P&G 
also suggested that, if the label statement is retained, it should 
explain why olestra has effects on vitamin absorption.
---------------------------------------------------------------------------

    \61\ Two examples of wording suggested by the comments are: 
``Because olestra interferes with your body from absorbing certain 
nutrients and the vitamins A, D, E, and K, these essential vitamins 
have been added to this product.'' and ``Olestra reduces the 
absorption of some nutrients, and vitamins A, D, E, and K have been 
added to compensate.''
---------------------------------------------------------------------------

    Based on consumer studies, FDA believes that the current label 
statement is not an effective means of communicating to consumers that 
olestra affects the absorption of fat-soluble vitamins or why vitamins 
A, D, E, and K are added to olestra-containing foods. As part of this 
rulemaking, the agency has concluded that a statement about olestra's 
effects on the absorption of fat-soluble vitamins is not needed in 
order to understand that olestra-containing foods do not contribute 
significant amounts of vitamins A, D, E, and K to the diet. Therefore, 
the agency believes that the label statement about olestra's effects on 
vitamin absorption should be eliminated, not simply re-worded. The 
agency does, however, believe that the label of olestra-containing 
foods must communicate that the vitamins A, D, E, and K added to such 
foods will not change consumers' vitamin status. Accordingly, this 
final rule requires the use of an asterisk and short explanatory 
phrase, ``Dietarily insignificant,'' a configuration that will 
communicate the intended message more clearly than the current 
statement. FDA notes that the petitioner concluded from consumer 
studies that the asterisk/statement configuration best communicates to 
consumers the fact that the vitamins A, D, E, and K added to olestra-
containing foods would have no net effect on consumers' vitamin status. 
It is also a format and configuration familiar to consumers because it 
is used in the Nutrition Facts panel and is similar to language used in 
other label statements (Sec. Sec.  101.60, 101.61, and 101.62).
    (Comment 21) A comment from a trade association to the 1996 final 
rule stated that the vitamin statement should be eliminated because the 
statement is a nutrient content claim for added vitamins and therefore 
violates Sec. Sec.  101.13, 101.54, and 101.9(c)(8)(ii). The comment 
stated that to satisfy a nutrient content claim for added vitamins, the 
product must provide an additional 10 percent of the reference daily 
intake (RDI) compared to a reference food. The comment claimed that 
vitamin addition to olestra would not always contribute an additional 
10 percent of the RDI for the added vitamins; therefore, the vitamin 
statement violates Sec. Sec.  101.13 and 101.54. The comment also 
argued that the label statement violates Sec.  101.9(c)(8)(ii) because 
any claimed nutrient must be included on the nutrition label. Under the 
current policy, the vitamins added to olestra are not included on the 
nutrition label.
    Because the olestra label statement will no longer be required to 
appear on the package of olestra-containing foods, whether the label 
statement contains a nutrient content claim is no longer an issue.
    (Comment 22) A comment from CSPI to the 1996 final rule recommended 
that the label statement advise consumers not to consume olestra with 
meals or vitamin supplements because such consumption would maximize 
nutrient loss. In contrast, a comment from P&G opposed such a label 
statement. In its comment, P&G cited preliminary data from its Active 
Surveillance Study showing that consumption of olestra-containing food 
does not result in any meaningful decrease in serum carotenoids. P&G 
also stated that the compensation levels of vitamins A, D, E, and K 
required by the agency are based on data reflecting worst-case 
consumption scenarios. P&G also noted that the majority of members of 
the FAC concluded in 1998 that there were no new data showing that 
olestra will adversely affect health by interference with the 
absorption of fat-soluble vitamins or other lipophilic substances.
    FDA does not agree that olestra-containing foods should be required 
to bear a label statement advising consumers against consumption of 
olestra with meals or vitamin supplements. FDA required the addition of 
vitamins A, D, E, and K to compensate for the known effects of olestra 
and established compensation levels that would be adequate for those 
individuals who consume olestra-containing snacks at meals. For 
carotenoids, FDA concluded in the 1996 final rule that there was no 
basis to require compensation of olestra-containing foods with specific 
carotenoids (61 FR 3118 at 3147-3149). Moreover, in its comments, CSPI 
provided no data to show that customary or usual consumption of 
olestra-containing snacks with meals or vitamin supplements causes 
nutrient losses that warrant a statement advising consumers not to 
consume olestra-containing snacks with meals or vitamin supplements.
    (Comment 23) A comment from CSPI to the 1996 final rule stated that 
the olestra label statement should include information directed toward 
those using coumarin derivatives to control blood clotting because 
there are no clinical data in the olestra petition showing that the 
addition of vitamin K to olestra-containing foods would be safe and 
efficacious for people who use coumarin derivatives. The comment also 
suggested that the label statement include information directed toward 
those with hemophilia or ``other blood diseases.'' A comment from 
academia also requested that the label statement provide information 
directed at those taking coumarin derivatives and cited an article in 
the New England Journal of Medicine (Ref. 36) as support for a warning 
label statement. The comment asserted that olestra's inhibition of 
vitamin K absorption could result in extreme elevation of prothrombin 
time and that patients taking this medication would need a careful and 
more frequent monitoring system to regulate and adjust drug 
administration. The comment also asserted that safety studies with 
olestra should be performed in patients taking coumarin derivatives. 
Another comment requested that the label statement indicate that 
olestra could cause blood clots, but provided no data or rationale to 
support this assertion.
    One comment opposed the use of ``hemophilia'' in statements 
directed toward users of coumarin derivatives, stating that vitamin K 
status is not a factor in hemophilia. The comment also opposed use of 
the phrase ``other blood diseases'' in any statement directed toward 
users of coumarin derivatives because it is too vague. The comment also 
stated that the routine monitoring by physicians of patients taking 
coumarin derivatives will result in alterations in drug dosing if major 
and persistent alterations of vitamin K-compensated olestra-containing 
food intakes are found to influence drug efficacy.
    FDA does not agree that olestra-containing foods should be required 
to bear a label statement directed toward those using coumarin 
derivatives to control blood clotting. FDA concluded in 1996 that 
consumption of olestra would not significantly influence the rate or 
extent of absorption of drugs (61

[[Page 46393]]

FR 3118 at 3132). Further, FDA stated that it did not expect olestra 
consumption to have a significant effect on the absorption of Coumadin, 
the most commonly prescribed form of coumarin (61 FR 3118 at 3132). As 
part of the 1996 final rule, FDA required olestra-containing foods to 
be compensated with 8 micrograms vitamin K1/g olestra so 
that consumption of vitamin K-compensated foods will have no net effect 
on vitamin K status (61 FR 3118 at 3167). FDA also concluded in 1996 
that any change in vitamin K status due to consumption of vitamin K-
compensated olestra would likely be within the normal range of dietary 
variation (61 FR 3118 at 3147). The comments do not provide the agency 
with any evidence that vitamin K-compensated olestra would cause 
changes in vitamin K status beyond the normal range of dietary 
variation or that olestra would affect the absorption of coumarin 
derivatives. Thus the agency has no basis to require labeling directed 
to those individuals using coumarin derivatives to control blood 
clotting.
    (Comment 24) A comment from Frito-Lay to the current petition as 
well as comments from P&G, Frito-Lay, and academia to the 1996 final 
rule stated that the phrase ``other nutrients'' should be eliminated 
from the label because the health benefits associated with consumption 
of fruits and vegetables have not been specifically attributed to 
carotenoids and consumer perception studies show that consumers are 
confused as to its meaning. One comment added that current evidence 
does not show that inhibition of carotenoid absorption has any 
nutritional significance. One comment stated that this phrase creates a 
misperception of a lack of safety and serves no purpose because 
carotenoids are neither specifically mentioned nor added back. P&G and 
Frito-Lay both reported that data from consumer studies show that the 
phrase ``other nutrients'' is not informative and may be 
misinterpreted.
    A comment from academia to the 1996 final rule criticized the focus 
group study submitted by P&G, stating that the participants were not 
adequately informed about the depletion of blood carotenoids and the 
evidence relating low blood carotenoids to risks of serious major 
health outcomes; therefore, this comment concluded that the results of 
the focus group study are ``specious.''
    FDA agrees that the phrase ``other nutrients'' should be eliminated 
from the label statement. Information from consumer perception studies 
shows that the label's contextual statement about ``some vitamins and 
other nutrients'' tends to mislead consumers and the contextual 
information is not necessary to understand that olestra-containing 
foods do not contribute significant amounts of vitamins A, D, E, and K 
to the diet.
    In the 1996 final rule, FDA did not require a specific statement on 
carotenoids because doing so could falsely imply that their decreased 
absorption is known to be of significance (61 FR 3118 at 3161). FDA 
determined in the 1996 final rule that the data and information 
available to the agency do not establish any identifiable nutritional 
or prophylactic benefits for carotenoids, with the exception of their 
provitamin A effects (61 FR 3118 at 3149). Thus, FDA does not agree 
that the results of the focus group studies are ``specious'' because 
participants were not informed of possible health consequences of 
decreased levels of blood carotenoids.
    (Comment 25) A comment from CSPI to the current petition asserted 
that the olestra label statement should indicate that olestra 
consumption may reduce the absorption of carotenoids and that 
carotenoids may protect against certain chronic illnesses. 
Alternatively, the comment stated that FDA should require fortification 
of olestra-containing foods with the relevant fat-soluble carotenoids. 
The comment asserted that olestra's effect on carotenoid levels is a 
material consequence that may result from customary consumption and 
that the olestra label statement would be misleading without a 
statement about carotenoid loss. The comment cited P&G's two 8-week 
studies as well as two published articles describing human studies \62\ 
conducted with sucrose polyester and asserted that all of these studies 
showed substantial decreases in serum carotenoids associated with 
olestra consumption. CSPI quotes statements from the two published 
studies conducted with sucrose polyester indicating that the effects of 
sucrose polyester on carotenoids are undesirable. CSPI also quotes from 
an invited commentary on one of the studies. The commentary states that 
the deleterious effects of sucrose polyester should be studied further 
before it is widely available for long-term consumption (Ref. 38). CSPI 
also stated that there is growing evidence that carotenoids provide a 
health benefit, citing studies reviewed by Dr. Graham Colditz at the 
1998 FAC meeting and three other research articles submitted to the 
docket by another comment (Refs. 39 through 41). CSPI added that 
consumers need information concerning carotenoid absorption because 
they cannot monitor depletion of their carotenoids, and detection of 
health changes caused by carotenoid depletion may occur only after 
irreversible damage has taken place. Finally, CSPI stated that the 
agency should base its decision on the potential nutritional effects of 
daily consumption of olestra, as documented by the preapproval clinical 
studies.
---------------------------------------------------------------------------

    \62\ One of the articles cited by CSPI is described in section 
VI.A (Ref 34). The other article cited by CSPI describes two studies 
(Ref. 37). The first study was a double-blind, placebo-controlled 
crossover study in which subjects received, through margarine, zero 
or 12.4 g of sucrose polyester per day for 4 weeks. The second study 
was a double-blind, placebo-controlled parallel comparison study in 
which subjects received, through margarine, zero or 3 g of sucrose 
polyester per day for 4 weeks. Both studies measured the effect of 
the treatments on plasma carotenoid concentration. The article does 
not include information (such as specifications) to determine the 
similarity between the sucrose polyester tested and olestra.
---------------------------------------------------------------------------

    Similarly, in its comments to the 1996 final rule, CSPI suggested 
that the phrase ``other nutrients'' should be expanded to advise 
consumers that olestra has been shown to decrease blood levels of 
carotenoids. The comment also stated that the label statement should 
include statements about the types of conditions that carotenoids may 
help prevent, such as cancer and blindness. The comment reported that 
the majority of carotenoid experts contacted by CSPI agreed that 
depletion of carotenoids is likely to pose hazards or risk of harm to 
health. The comment also cites the 1995 edition of the ``Dietary 
Guidelines for Americans'' issued on January 2, 1996, jointly by the 
Department of Agriculture and the Department of Health and Human 
Services. CSPI stated that the guidelines say that antioxidants such as 
carotenoids are of interest because they may have a beneficial role in 
reducing the risk of cancer and certain other chronic diseases. CSPI 
asserts that if evidence of carotenoids' value in protecting health is 
sufficient to warrant such a statement by the Department of Health and 
Human Services, it should be sufficient for FDA to inform consumers 
that olestra depletes carotenoids. CSPI also argued that depletion of 
carotenoids is a side effect that the public cannot monitor and the 
public needs information on side effects in order to decide whether to 
buy olestra-containing foods.
    In contrast to CSPI's comments, a comment to the 1996 final rule 
specifically opposed use of the words ``causing cancer or blindness'' 
on the label statement because the words put olestra in the category of 
cigarettes and expressed the opinion that olestra did

[[Page 46394]]

not belong in the same category as cigarettes, but provided no factual 
information or rationale in support of the opinion expressed.
    FDA does not agree that olestra-containing foods should be required 
to bear a label statement indicating that consumption of these foods 
may reduce the absorption of carotenoids and that carotenoids may 
protect against certain diseases, nor does FDA agree that it should 
require addition of specific carotenoids to olestra-containing foods. 
Current evidence supports the connection between the consumption of 
fruits and vegetables (many of which contain carotenoids) and reduced 
risk for certain diseases. The available data do not, however, 
establish any identifiable nutritional or prophylactic benefits 
specifically for carotenoids, either individually or collectively (61 
FR 3118 at 3149) other than their provitamin A function. This position 
is consistent with the conclusions of the 2000 report of the IOM Panel 
on Dietary Antioxidants and Related Compounds which found no basis for 
establishing a DRI for beta-carotene or other carotenoids.\63\ The 1995 
``Dietary Guidelines for Americans'' recommend healthy dietary habits, 
including eating fruits and vegetables, but do not present any new 
scientific information related to possible beneficial health effects 
specifically attributed to the consumption of carotenoids. Based on the 
lack of an identifiable nutritional or prophylactic benefit for 
carotenoids (other than their provitamin A activity), FDA has no basis 
at this time to require a label statement about carotenoids and their 
potential health effects or to require the addition of specific 
carotenoids to olestra-containing foods.\64\
---------------------------------------------------------------------------

    \63\ FDA notes that in its report, the panel considered the 1999 
research articles referred to by CSPI (Refs. 39 through 41).
    \64\ FDA notes that the addition of vitamin A to olestra-
containing foods compensates for any provitamin A losses caused by 
the inhibitory effect of olestra on carotenoid absorption.
---------------------------------------------------------------------------

    FDA determined in its 1996 final rule that, based on the existing 
scientific evidence, including the 8-week studies examining the 
nutritional effects of daily olestra consumption, that there was no 
justification or need to require compensation of olestra-containing 
foods with specific carotenoids (61 FR 3118 at 3149). The data and 
information obtained since the time of the 1996 final rule do not 
change the agency's 1996 conclusion.
    The issue of olestra's effect on carotenoids was discussed by the 
FAC in both 1995 and 1998. Most members of the FAC agreed in 1995 that 
the effect of olestra on the bioavailability of carotenoids is not a 
fact that is material in light of the consequences that may result from 
consumption of olestra-containing foods and therefore the effect does 
not warrant disclosure on the label of such foods (61 FR 3118 at 3162). 
Subsequently, in 1998, a majority of the FAC expressed the view that 
there were no new data to show that the potential effect of olestra on 
carotenoids represents a public health concern.\65\
---------------------------------------------------------------------------

    \65\ Transcript, vol. 3, pp. 101-174.
---------------------------------------------------------------------------

    (Comment 26) A comment from academia to the current petition stated 
that the issue of olestra, carotenoids, and chronic disease should be 
considered by an impartial body such as the NAS to determine whether 
there is reasonable certainty that reductions in carotenoid levels will 
not increase the risk of various diseases. The comment states that the 
approval process for olestra was flawed because in the first review, 
the committee did not include cancer or nutritional epidemiologists or 
other experts who are qualified to review the issue of carotenoid 
intake and its effect on risk of chronic disease. The comment also 
stated that in the second review, the committee did not consider 
evidence considered by the first committee, but only considered new 
evidence.\66\ The comment asserted that since the June 1998 FAC 
meeting, there have been a substantial number of publications 
indicating that low carotenoid status may be linked to increased risk 
for certain diseases and included copies of three published articles on 
carotenoids.\67\ The comment also states the results of a 1996 survey 
of 13 members of the NAS Committee on Diet, Nutrition, and Cancer who 
authored the 1982 review of Diet, Nutrition, and Cancer.\68\ The survey 
asked the following questions: (1) ``Are you reasonably certain that 
carotenoids contained in fruits and vegetables are not related to the 
apparent benefits of these foods in reducing cancer risk?'' and (2) 
``Are you reasonably certain that reductions in blood levels of 
carotenoids will not increase the risk of cancer?'' The comment stated 
that seven members answered ``no'' to both questions and that not one 
member could affirm that they could be reasonably certain that 
reductions in blood carotenoids would not increase cancer risk. Based 
on the results of the survey, the comment concluded that the FDA's 
conclusion of olestra's ``reasonable certainty of no harm'' is not 
supported by expert scientific opinion. The comment asserted that the 
effects of carotenoids are poorly understood and we cannot be 
reasonably confident that reduction in blood carotenoid levels will 
cause no harm. The comment also stated that the logic that we cannot be 
certain whether it is the carotenoids in fruits and vegetables that are 
protective against disease violates the precautionary principle and 
FDA's guideline of reasonable certainty of no harm because the burden 
of proof should be on the petitioner to show that carotenoids are not 
the protective factors in fruits and vegetables.
---------------------------------------------------------------------------

    \66\ FDA assumes that the first review referred to by the 
comment is the 1995 meeting of the OWG and FAC and that the second 
review referred to by the comment is the 1998 meeting of the FAC.
    \67\ The publications submitted with the comment are the same as 
those discussed in the previous comment (Refs. 39 through 41).
    \68\ The survey was conducted in May 1996 by Drs. Walter Willett 
and Meir Stampfer of the Department of Nutrition, Harvard School of 
Public Health.
---------------------------------------------------------------------------

    This comment raises the issue of whether olestra's use in savory 
snacks is safe (section 409(c) of the act), given the potential effects 
of olestra consumption on serum carotenoids levels. This issue is 
beyond the scope of the petition before FDA which concerns labeling. 
FDA notes that even if the comment is correct that olestra's use in 
savory snacks is unsafe due to the additive's effect on serum 
carotenoids, such lack of safety cannot be rectified through labeling. 
Indeed, as noted, in the 1996 final rule, FDA concluded that olestra is 
safe for use in savory snacks, a conclusion reached after a review of 
the evidence in the record concerning carotenoids and human health. If 
the comment wishes to have FDA consider this safety issue, they must 
file a citizen petition requesting such consideration, 21 CFR 10.30, 
not raise it as a collateral issue in this proceeding. FDA addresses 
the issue of labeling for olestra's effect on carotenoids in its 
response to the previous comment. FDA addresses the issues raised about 
the 1995 meeting of the OWG and FAC and the 1998 meeting of the FAC in 
response to comment 43 of this document.

C. Labeling for Special Populations

    (Comment 27) Some comments to the current petition stated that the 
olestra label should include a statement that olestra-containing foods 
should not be given to children. One comment stated that olestra should 
be marketed in childproof containers or the food label should include 
the statement ``Keep out of reach of children.'' One comment expressed 
concern that there is a lack of testing and evaluation of olestra in 
young children, and that even small packages may be a relatively high 
dose in children when considered on the basis of grams of olestra per 
kilogram of body weight. Two comments reported

[[Page 46395]]

GI reactions of a child who had consumed an olestra-containing food.
    CSPI submitted comments to the 1996 final rule requesting that the 
olestra label contain statements directed toward certain populations of 
consumers. In particular, CSPI stated that the label statement should 
contain special notification for children and for the elderly because 
olestra is poorly studied in children and there are inadequate data 
regarding the possible hazards of olestra consumption over both the 
long and short terms. The comment also quoted a 1995 FDA review 
memorandum of the petitioner's preapproval Fecal Parameters Study which 
expresses concern for two populations not represented in the study, the 
elderly and young children, because of the potential for increased 
water loss through the stool of subjects reporting olestra-associated 
diarrhea (Ref. 22). CSPI also stated that the label of olestra-
containing foods should include statements directed toward pregnant 
women because there are inadequate data regarding the safety of olestra 
for use by pregnant women. CSPI suggested that the label statement 
indicate that those with inflammatory bowel diseases, irritable bowel 
diseases, and malabsorption disorders should contact a physician before 
eating olestra-containing foods because, in CSPI's opinion, the study 
of inflammatory bowel disease patients was too small and too brief to 
determine conclusively that olestra is safe for people with these 
illnesses.
    FDA does not agree that the agency should require olestra-
containing foods to bear a label statement directed toward special 
populations. In the 1996 final rule (61 FR 3118 at 3156-3157), the 
agency stated its conclusion that olestra was safe for use by children. 
Three studies submitted in support of the original petition reported GI 
symptoms in the young. FDA noted that GI symptoms seen in children were 
similar to those seen in the 8-week studies of adults. FDA concluded 
that the safety of olestra for use by children could be addressed by 
extrapolating the GI effects in adults to the young. This approach was 
fully consistent with the expert views provided by the OWG and the 
members of the FAC. Further, the petitioner's Home Consumption Study 
submitted in support of the current petition shows no olestra-related 
effects in the group of subjects younger than 18 years (Ref. 15). The 
comments provide the agency with no new data to show that olestra-
containing foods should not be consumed by children, or should be 
specially labeled or packaged for children.
    Similarly, FDA does not agree that olestra-containing foods should 
be required to bear a label statement directed toward the elderly. The 
agency is not aware of any safety issues specific to olestra-
consumption by the elderly, nor does the comment provide evidence of 
such issues. Since submission of this comment, the agency has received 
several postapproval studies from the petitioner that have included 
subjects over the age of 65. These studies have not identified any 
concerns specific to the elderly that would require specialized 
labeling.
    FDA does not agree with CSPI's conclusion that the agency's 
memorandum (Ref. 22), should drive the overall conclusion about the 
effects of consumption of olestra-containing food on children and the 
elderly. The agency considered this memorandum in its analysis of the 
original food additive petition on olestra (61 FR 3118 at 3155). In the 
1996 final rule, FDA concluded that the Fecal Parameters Study showed 
there is no difference in stool composition (e.g., water and 
electrolyte content) between those olestra-consuming subjects who 
reported diarrhea and those who did not (61 FR 3118 at 3155). In its 
overall conclusions on the effects of olestra on the GI tract, the 
agency stated that even those olestra-consuming subjects in the 
preapproval studies who experienced loose stools continuously for 
several weeks did not show any evidence of fluid loss, such as 
hemoconcentration or electrolyte imbalance (61 FR 3118 at 3159). Since 
publication of the 1996 final rule, P&G submitted the Stool Composition 
Study, which examined the effect of olestra on the water content of 
stools. The Stool Composition Study used a dose of olestra that was 
greater than the highest dose used in the Fecal Parameters Study and 
collected stools from study subjects for a longer period of time. As 
discussed previously, based upon the agency's evaluation of the Stool 
Composition Study, FDA has concluded that the GI effects observed are 
not clinically significant (Ref. 18), and that the stools study 
subjects characterized as ``diarrhea'' were not associated with an 
increase in stool water (Ref. 10).
    In addition, FDA does not agree that olestra-containing foods 
should be required to bear a label statement directed toward pregnant 
women. FDA concluded in 1996 that olestra is safe for its intended use 
in savory snacks (Sec.  172.867). FDA has no basis to conclude that 
there are consequences associated with the consumption of olestra that 
are specific to pregnant women. Importantly, the comment provides no 
information to demonstrate that olestra-containing foods present a 
unique risk to pregnant women.
    Finally, FDA does not agree that olestra-containing foods should be 
required to bear a label statement directed toward those with 
inflammatory bowel disease, irritable bowel disease, or malabsorption 
disorder. Once again, the comment provides no evidence to establish 
that there are consequences of olestra consumption specific to patients 
with inflammatory bowel disease, irritable bowel syndrome, or 
malabsorption disorder, that warrant special labeling. Moreover, FDA 
considered data regarding inflammatory bowel disease at the time of the 
1996 final rule. In particular, P&G conducted a study to address 
concerns as to whether the presence of olestra in the GI tract 
exacerbates the disease state of patients with inflammatory bowel 
disease. FDA acknowledged that the study of inflammatory bowel disease 
patients was limited in size and duration (61 FR 3118 at 3155-56). The 
study does, however, provide reassurance that consumption of 20 g 
olestra/d for up to 31 days did not cause an observable effect in 
populations with inflammatory bowel disease. In addition to this human 
study, the petitioner conducted studies to assess the potential for 
increased absorption of olestra in guinea pigs with compromised GI 
tracts containing lesions similar to those seen in ulcerative colitis 
and Crohn's disease. The studies showed that the absorption of intact 
olestra is no greater in guinea pigs with compromised GI tracts than in 
guinea pigs with normal GI tracts (61 FR 3118 at 3126-3127).
    (Comment 28) One comment from an individual consumer to the 1996 
final rule expressed concern that it is important for diabetics to know 
that sucrose is part of the olestra molecule.
    FDA disagrees with this comment. As discussed in the 1996 final 
rule, olestra is a chemical combination of sucrose with six, seven, or 
eight fatty acids (61 FR 3118 at 3118). While olestra is made from 
nutritive ingredients, only a minuscule amount of olestra is absorbed 
by the body (61 FR 3118 at 3120 at 3126-3127), and therefore, most of 
the sucrose present in olestra is not biologically available. 
Similarly, FDA noted that rats administered the formulation of olestra 
proposed for human consumption absorbed only 0.14 percent of the 
administered dose (61 FR 3118 at 3126). Thus, at most, only trivial 
amounts of sucrose could be obtained from the ingestion of olestra. FDA 
concluded in 1996 that all safety issues regarding olestra had been 
addressed

[[Page 46396]]

adequately and that the use of olestra in savory snacks is safe (61 FR 
3118 at 3168). The comment provides no evidence that the small amount 
of sucrose potentially obtained from olestra is hazardous to diabetics 
or warrants disclosure on the food label. Therefore, FDA concludes that 
there is no basis for the agency to require that the label of olestra-
containing foods disclose that olestra is made from sucrose.

D. Label Statement in Its Entirety

    (Comment 29) Frito-Lay and P&G submitted comments stating that the 
olestra label should be eliminated in its entirety and that the added 
vitamins should be labeled in the ingredient list with an asterisk and 
a statement such as ``*Not a nutritionally significant source.'' The 
comment from P&G to the 1996 final rule reported the findings of an 
expert panel it convened to examine whether the label statement should 
be maintained. The comments from both Frito-Lay and P&G provided 
arguments for the elimination of the GI and nutritional effects 
statements. FDA responded to these arguments in the previous sections 
discussing comments on the GI and nutritional effects statements. Both 
comments argued that the current scientific evidence does not support 
retention of the label statement and that the label is misleading. 
Frito-Lay also pointed out that the sentence ``This product contains 
olestra.'' is not needed in the label statement because olestra is 
listed in the ingredient statement, and manufacturers that use olestra 
generally place the logo of the olestra brand name, Olean, on the front 
panel of olestra-containing foods.
    In contrast, a comment from CSPI to the current petition supported 
the retention of a label statement. In its comment CSPI proposed the 
following label statement enclosed in a box:

    THIS PRODUCT CONTAINS OLESTRA. Olestra may cause abdominal 
cramping and loose stools in a small percentage of consumers. If you 
experience adverse effects that may be caused by olestra, call 1-
800-OLESTRA. If your symptoms persist or are severe, contact a 
health professional. Frequent consumption of olestra may reduce your 
body's absorption of fat-soluble nutrients (carotenoids). 
Carotenoids, found in fruits and vegetables, may protect you against 
certain chronic illnesses.\69\
---------------------------------------------------------------------------

    \69\ FDA notes that since the 1996 final rule, CSPI has 
submitted several versions of a suggested label statement. The 
version presented is CSPI's most recent version. Previous versions 
are generally characterized as including a greater number of 
possible GI symptoms, statements about olestra's effect on the 
absorption of vitamins A, D, E, and K, statements that loss of 
carotenoids may increase the risk of certain health conditions, and 
statements directed toward special populations (such as children, 
patients taking Coumadin, and those with bowel disorders).

    CSPI argued that a nondescript declaration of the word ``olestra'' 
in the ingredient listing does not inform consumers of the side effects 
of consuming olestra, and unless consumers are aware of the potential 
side effects, they would have no reason to consult the ingredient list 
to determine if a food contains olestra. CSPI asserted that a similar 
concern was raised about the use of the terms ``pasteurized'' or 
``unpasteurized'' in the preamble to the final rule requiring warning 
label statements for unpasteurized juices (63 FR 37030, July 8, 1998). 
CSPI pointed out that the final rule stated that some consumers do not 
know the significance of pasteurization and therefore would not be able 
to make an informed decision on whether to purchase and consume the 
products and that use of the term ``pasteurized'' or ``unpasteurized'' 
alone would not give consumers information about the risks presented by 
untreated juices (63 FR 37030 at 37034). CSPI noted that the final rule 
for labeling of unpasteurized juices argues that the presence of some 
pathogens that have been responsible for recent outbreaks of food borne 
illnesses associated with untreated juice products is a relatively new 
phenomenon. Therefore, consumers do not associate such pathogens and 
the risks they present with the consumption of untreated juice (63 FR 
37030 at 37032-33). CSPI asserted that label statements for olestra are 
necessary to inform consumers of the unexpected, potential consequences 
of consuming foods that have long been consumed without adverse effects 
and that simply disclosing the presence of olestra in the ingredient 
statement does not inform consumers of olestra's potential side 
effects.
    FDA agrees with the comments from Frito-Lay and P&G that olestra-
containing foods should no longer be required to bear a label 
statement. FDA concluded in the 1996 final rule that olestra was safe 
for its intended use in savory snacks. As part of the 1996 final rule, 
FDA required a label statement to appear on olestra-containing foods. 
The label statement was required to inform consumers of the potential 
for olestra to cause GI effects and because consumers had no experience 
with this food ingredient. The label was also required in order to 
prevent consumers from erroneously concluding that the vitamins added 
to olestra-containing foods would contribute significant amounts to 
their diet when, in fact, these vitamins were added to offset any 
vitamin losses caused by the consumption of olestra-containing foods. 
The rationale used in the labeling of untreated juice products cannot 
be directly applied to the labeling of olestra-containing foods because 
untreated juice products were labeled to warn consumers of potential 
health hazards such as serious illness, while olestra-containing foods 
were labeled to inform consumers of potential effects that do not 
represent health hazards.
    In determining the wording of the warning statement for 
unpasteurized juices, FDA determined from focus group research that 
most participants had a good understanding of what pasteurization was, 
but a significant number of participants did not (63 FR 37030 at 
37034). The agency also concluded that use of the terms ``pasteurized'' 
or ``unpasteurized'' alone would not give consumers information about 
the risks presented by untreated juices (63 FR 37030 at 37034). In 
contrast, as discussed previously, postapproval consumer perception 
studies and tracking surveys show that there is currently a high degree 
of awareness about olestra and its ability to cause GI effects. Indeed, 
it appears that consumers are more likely to overestimate rather than 
underestimate the potential for olestra to cause GI effects. FDA does 
not typically require label statements for products that may cause GI 
symptoms when consumers are aware that such foods may cause such 
effects. As noted in the response to previous comments, FDA does not 
believe that the label of olestra-containing foods should be required 
to contain information about the effect of olestra on serum carotenoid 
levels. FDA will require that vitamins A, D, E, and K added to olestra 
be labeled in the ingredient list with an asterisk and the phrase 
``Dietarily insignificant'' to prevent consumers from being misled to 
believe that the added vitamins contribute significant amounts to the 
diet.
    (Comment 30) Many comments to the current petition specifically 
stated that olestra-containing foods should bear a label statement. 
Most of these comments were from consumers who reported experiencing GI 
reactions that they associated with consuming olestra-containing foods. 
One comment stated that the label statement was important in 
identifying the cause of their GI symptoms. Another comment expressed 
concern that there is insufficient knowledge about olestra. Another 
comment stated that a side effect such as severe abdominal cramping and 
diarrhea should be made known to

[[Page 46397]]

people who consume olestra, because such symptoms can have significant 
clinical effects on patients with many different medical conditions.
    In addition, some comments to the 1996 final rule specifically 
stated that olestra-containing foods should bear a special label 
statement. One comment stated that the label statement required by the 
1996 final rule is clear and should be retained. One comment supported 
the need for labeling by citing reports from a number of constituents 
who had consumed olestra-containing foods and had experienced severe GI 
reactions that they believe were caused by olestra. Other comments 
requested that olestra-containing foods bear a label statement so that 
these products can be avoided.
    As explained previously, FDA has concluded that olestra-containing 
foods should no longer be required to bear a label statement. FDA does 
not agree that it should require special labeling for olestra-
containing foods on the basis that consumers are not familiar with 
olestra and the potential GI symptoms it may cause. In reaching its 
decision on this food additive petition, FDA considered the public's 
awareness of olestra's potential to cause GI effects. As stated 
previously, the postapproval consumer perception studies and the 
tracking surveys show that there is currently a high degree of 
awareness about olestra and its potential to cause GI effects. FDA does 
not typically require special labeling of products that may cause GI 
symptoms when consumers are aware that such foods may cause such 
effects. FDA notes that, even in the absence of the label statement, 
consumers who wish to avoid olestra will still be able to identify 
olestra-containing foods because olestra is required to be declared in 
the ingredient list of such products.
    The agency concluded in 1996 that olestra was safe for use in 
savory snacks and that olestra's GI effects were not adverse health 
effects (61 FR 3118 at 3159). The comments reporting GI reactions 
provide no basis to conclude that the GI symptoms reported are actually 
caused by olestra. The new data and information submitted by the 
petitioner show that customary or usual olestra consumption causes no 
increase in the frequency of abdominal cramps and only a minor increase 
in the frequency of loose stools and bowel movements and that these 
effects do not have a meaningful impact on daily activity. Moreover, 
the petitioner's most recent studies show that the label statement 
could be misleading and cause consumers of olestra to attribute serious 
problems to olestra when this is unlikely to be the case.
    (Comment 31) Some comments from individual consumers to the current 
petition stated that olestra-containing foods should bear a label 
statement because the public has a right to know about the potential 
side effects of olestra-containing foods.
    FDA notes that the act does not provide the agency with the 
authority to require labeling simply because consumers appear to want 
such information. (See Stauber v. FDA, 895 F. Supp 1178, 1193 
(N.D.Wisc. 1995); Alliance for Biointegrity v. Shalala, 116 F. Supp 
166, 179 (DDC Sept. 29, 2000).) FDA could require the suggested 
labeling if, without such labeling, the product labeling failed to 
reveal facts that are material in light of the consequences which may 
result from the conditions of use prescribed in the labeling or under 
conditions of use that are customary or usual.
    (Comment 32) A comment from Frito-Lay to the 1996 final rule stated 
that the label statement should contain only a message directing 
consumers to a telephone number for more information instead of the 
current label statement. The Frito-Lay comment cited a consumer study 
showing that none of the label statements evaluated in the study 
eliminated consumer misperception and that consumers interpreted the 
current label statement as a safety warning. The comment concluded that 
this type of labeling, however worded, has a strong negative effect on 
the consumer's perception of the safety of olestra-containing foods. In 
a comment to the 1996 final rule, P&G stated that as an alternative to 
the nutritional effects statement or the labeling of the added vitamins 
in the ingredient list with an asterisk, the agency could consider 
requiring manufacturers to provide a telephone number for consumers to 
obtain nutritional information. In its comments to both the current 
petition and the 1996 final rule, CSPI stated that the label statement 
should include a telephone number for consumers to obtain more 
information or to report adverse effects.
    FDA does not agree that it should require the labeling of olestra-
containing foods to include a telephone number. As explained 
previously, FDA has concluded that olestra-containing foods should no 
longer be required to bear a label statement and that vitamins A, D, E, 
and K required to be added to olestra-containing foods should be 
labeled in the ingredient list with an asterisk that refers to the 
statement ``Dietarily insignificant.'' FDA is requiring this labeling 
to ensure consumers understand that such foods do not contribute 
significant amounts of the vitamins A, D, E, and K to the diet. FDA 
does not agree that it should require manufacturers to provide a 
telephone number in place of this information. FDA believes that there 
is no basis to require that the label for olestra-containing foods 
include a telephone number for consumers to obtain more information or 
report adverse effects, nor do the comments explain why such a number 
is necessary to prevent the misbranding of these foods. FDA recognizes 
that some firms voluntarily include telephone numbers on their food 
labels. For those products that do not contain a telephone number, 
consumers may obtain more information or report adverse effects by 
contacting the company using the company's name and address, both of 
which are required to appear on the food label in accordance with Sec.  
101.5.

E. Data and Information Considered in This Rulemaking

    (Comment 33) A comment from CSPI to the current petition stated 
that the postapproval studies should be considered, but they should not 
supersede or override the preapproval studies. The comment asserted 
that the postapproval studies are not a reason to reject all the 
previous evidence that olestra can cause GI symptoms. The comment also 
asserted that the lack of adverse effects reported during P&G's 
postapproval studies may be due to the small doses of olestra consumed, 
relative to the preapproval studies, and that rules should be based on 
the possibility that a greater number of olestra-containing foods would 
be consumed more frequently in the future. CSPI also stated that the 
postapproval studies cannot disprove that olestra-containing foods 
cause adverse effects in a small percentage of consumers.
    In deliberations on this petition, FDA has considered all evidence 
of record (including both preapproval and postapproval studies). The 
agency notes that the petitioner's postapproval studies are meant to 
complement, not supersede, the preapproval studies. The preapproval 
studies were designed to address safety while the postapproval studies 
were, with the exception of the Stool Composition Study, designed to 
address labeling.
    FDA's 1996 decision to require special labeling of olestra-
containing foods was based on preapproval studies which were designed 
to address the safety standard for food ingredients--reasonable 
certainty of no harm under the intended conditions of use (Sec.  
170.3(i)). These studies examined the

[[Page 46398]]

effect of conditions of use that did not reflect expected intake and 
thus, do not provide information about the effects of olestra 
consumption under customary or usual conditions. In contrast, the 
petitioner's recent Acute Consumption Study, Home Consumption Study, 
and Rechallenge Study more closely address the factual predicate of the 
legal standard for requiring special labeling--facts that are material 
with respect to consequences which may result under the conditions of 
use prescribed in labeling or advertising or under such conditions of 
use that are customary or usual (section 201(n) of the act). Thus, FDA 
concludes that the petitioner's preapproval studies should be 
considered, but they must be considered in light of the postapproval 
studies which more directly address whether olestra-related effects 
warrant special labeling.
    During FDA's review of P&G's petition for the use of olestra in 
savory snacks, FDA assumed that olestra-containing foods may be 
consumed more frequently than they are presently. For example, when 
estimating daily intake of olestra from savory snacks, the agency 
assumed that all savory snacks consumed would be olestra-containing 
savory snacks (61 FR 3118 at 3125). Such conservative assumptions are 
likely to over-estimate consumption.
    Olestra is currently approved for use as a fat substitute only in 
ready-to-eat savory snacks. Any additional use will require agency 
approval through the food additive petition process in accordance with 
Sec.  171.1 (21 CFR 171.1). When considering the approval of olestra 
for additional uses, FDA will consider consumers' cumulative exposure 
to olestra through the currently approved uses (savory snacks) as well 
as through any additional uses requested.
    The question raised by this petition is not simply whether olestra 
causes GI effects, but whether customary or usual olestra consumption 
causes GI effects that warrant special labeling. As mentioned 
previously, while no study can rule out the possibility that olestra 
may cause GI effects in a small percentage of consumers, the 
petitioner's postapproval studies do show that customary or usual 
consumption of olestra-containing savory snacks does not cause GI 
symptoms with a frequency, severity, or impact on daily activity that 
warrant special labeling.
    (Comment 34) A comment from CSPI to the current petition cited a 
study (Ref. 42) showing that consumption of 40 g olestra/day resulted 
in levels of fecal fat commonly observed in patients with steatorrhea 
caused by malabsorption syndrome. CSPI quoted the researchers' concerns 
that physicians may suspect malabsorption syndrome in patients who 
consume olestra and subject them to unnecessary diagnostic tests. CSPI 
stated that while the results of the study alone may not warrant label 
statements they should be factored in with studies demonstrating 
olestra's effects on nutrient levels and GI symptoms.
    Consideration of the study cited by CSPI does not change the 
agency's decision on this food additive petition. CSPI does not explain 
how the study should be considered in the context of labeling or why 
the results warrant special labeling of olestra-containing foods. CSPI 
provides no reason to believe that customary or usual olestra 
consumption has resulted in patients having to undergo unnecessary 
diagnostic tests for malabsorption syndrome or that malabsorption 
syndrome has been incorrectly diagnosed because of customary or usual 
olestra consumption.\70\ FDA notes that the study cited in the comment 
serves to alert physicians to the potential effects of olestra 
consumption on the measurement of fecal fat so that such misdiagnoses 
may be avoided.
---------------------------------------------------------------------------

    \70\ Subjects in the study cited by CSPI were fed 40 g olestra 
per day for 6 days. Based on the agency's preapproval estimate of 
olestra consumption, this level of olestra consumption is unlikely 
to be achieved under customary or usual consumption conditions. 
FDA's preapproval estimate of chronic daily olestra intake was 7 g/
p/d at the 90th percentile snack eater and 20 g/p/d for short-term 
``high'' consumption consumers (61 FR 3118 at 3124-3125). The 
estimate of chronic daily olestra intake assumes that olestra will 
be consumed at this level every day. FDA estimated that a ``high'' 
short-term consumer would consume olestra at a level equivalent to 
eating a 2 oz bag of olestra chips each day for 12 weeks (61 FR 3118 
at 3124-25).
---------------------------------------------------------------------------

    (Comment 35) A comment from CSPI to the current petition addressed 
a statement that P&G made in its petition that the First Amendment, 
which includes the right not to speak, may bar the requirement of 
anything other than material information or information deemed 
essential under the act to appear on the food label. In its comment, 
CSPI stated that consumers must be informed of the possible side 
effects of olestra-containing foods so that they can avoid needless 
medical treatment or avoid the possibility of suffering side effects 
altogether. CSPI also stated that the disclosure of potential side 
effects provides material information and is ``reasonably related'' to 
the agency's interest in preventing misleading food labels. Therefore, 
in CSPI's view, the label statement does not violate the First 
Amendment right not to speak, as asserted by the petitioner.
    FDA did not rely on the petitioner's First Amendment argument in 
concluding that olestra-containing products should no longer be 
required to bear the label statement required by the 1996 final rule. 
The issue raised by the current petition and the comment is whether 
olestra-related side effects are consequences of customary or usual 
olestra consumption that require disclosure in labeling. As stated 
previously, the agency has concluded that olestra-related side effects 
do not warrant required labeling because these effects are not 
consequences of customary or usual olestra consumption, and the comment 
provides no such data or information to demonstrate the contrary.
    (Comment 36) A comment from CSPI to the current petition pointed 
out that the petition states that FDA may decline to require disclosure 
of material information when to do so would crowd other important 
information or confuse consumers. CSPI argued that a label statement 
revised for increased clarity would not confuse consumers, and snack 
food packages are large enough to provide a label statement without 
crowding other important information.
    As noted, this final rule requires that the label of olestra-
containing foods list vitamins A, D, E, and K in the ingredient 
statement followed by an asterisk and the phrase ``Dietarily 
insignificant.'' FDA has determined that, for the remainder of the 
label statement required by the 1996 final rule, the underlying factual 
basis no longer exists and thus, is removing the relevant requirement 
from Sec.  172.867. These changes in the requirements for labeling of 
olestra-containing foods render moot the issue of ``label crowding.''

F. Safety of Olestra

    (Comment 37) Several comments from individual consumers to the 
current petition stated that olestra-containing foods should no longer 
be sold. One comment stated that olestra-containing foods should no 
longer be sold because even a more prominent label statement would not 
prevent illness in those who ingest such products in situations where 
the products are served in unlabeled containers. These comments relayed 
GI reactions that were attributed to olestra. A comment from CSPI 
stated that other countries have not approved petitions for the use of 
olestra and that such decisions not to approve olestra should provide 
some guidance as to how a substance like olestra should be regulated.

[[Page 46399]]

    A comment from CSPI to the 1996 final rule suggested that the label 
should include a statement indicating that the long-term effects of 
olestra consumption are not known. The comment expressed concern that 
the human studies were too brief compared to the length of time people 
will be eating olestra-containing foods and stated that the problems 
observed in the human and animal studies warrant a broader advisory 
about the possible long-term effects of olestra consumption. CSPI also 
stated that labeling should be complemented with point-of-purchase 
health-hazard information and mass media consumer information 
campaigns. Comments from manufacturers of baked snacks expressed 
concern that without clear labeling consumers will believe that 
olestra-containing foods are as safe as baked snacks.
    In comments to the 1996 final rule, CSPI and an individual consumer 
requested that the label statement be placed on restaurant menus so 
that diners will not unknowingly consume olestra at a restaurant.
    FDA disagrees with these comments. FDA concluded in the 1996 final 
rule that the use of olestra in savory snacks meets the safety standard 
for food additives, reasonable certainty of no harm (61 FR 3118 at 
3167). The label statement required by the 1996 final rule was never 
intended to prevent illness or warn against conditions of use that may 
be harmful as the agency concluded in 1996 that olestra is safe for its 
intended use in savory snacks even without the label statement. FDA 
required that olestra-containing foods bear the label statement to 
provide information about the presence of the vitamins listed in the 
ingredient statement and about potential nutrient and GI effects of 
olestra. FDA determined that these statements were necessary at the 
time to ensure that olestra-containing foods are not misbranded within 
the meaning of the act (61 FR 3118 at 3168).
    Because olestra-containing foods are safe even in the absence of 
the label statement, olestra-containing foods served in unlabeled 
containers or in a restaurant do not represent a health risk. FDA has 
no evidence to confirm that there is a group of individuals who are so 
sensitive or intolerant to olestra when it is consumed under customary 
or usual conditions that such consumption presents a health concern or 
warrants special labeling. In fact, the petitioner's Rechallenge Study 
shows that when consumers who reported effects that they attributed to 
olestra, were rechallenged with olestra chips, they were no more likely 
to report GI symptoms compared to when they were challenged with 
triglyceride chips.

G. Allergenicity of Olestra or Olestra-Containing Foods

    (Comment 38) A comment from CSPI to the current petition stated 
that while there is no reason to think that olestra itself causes 
allergic reactions, the agency or the petitioner should conduct tests 
to determine whether a contaminant in olestra, or another ingredient in 
olestra-containing chips, causes allergic reactions because allergic 
responses were reported. The comment added that FDA cannot design an 
accurate label statement until such studies have been conducted.
    FDA does not agree that allergenicity testing of olestra or 
olestra-containing foods must be conducted before ruling on this 
petition. The agency addressed the potential allergenicity of olestra 
in the 1996 final rule (61 FR 3118 at 3166). Food allergens are 
generally known to be protein or glycoprotein in nature. Olestra, 
composed of six, seven, or eight fatty acids esterified to sucrose, is 
neither a protein nor a glycoprotein and does not contain these 
substances even as minor constituents. The comment provides no basis to 
alter FDA's original conclusion that olestra is unlikely to cause 
allergic reactions.
    FDA acknowledges that some reports allege that unspecified allergic 
reactions or symptoms of allergic reactions were caused by an olestra-
containing food. The comment provides no evidence or reason to conclude 
that the effects reported were caused by olestra. FDA notes that a 
published article reports that when individuals who reported an 
allergic reaction to olestra were rechallenged, none of the individuals 
were found to have a positive response to olestra upon eating olestra-
containing potato chips or when given a skin prick test with olestra 
(Ref. 43).
    FDA notes that olestra-containing foods, like non-olestra-
containing foods, contain other ingredients that may be allergens to 
some individuals. Consumers are informed of the presence of such 
potential food allergens through the product ingredient statement, as 
is the case for products containing potentially allergenic substances 
like milk and eggs.

H. Nutrition Labeling and Claims

    (Comment 39) A comment from CSPI to the current petition asserted 
that the amount of olestra contained in snacks should be declared in 
the Nutrition Facts label. The comment stated that the amount of total 
fat per serving should be listed with an asterisk pointing to a note 
stating, ``This product contains x grams of olestra, which is not 
digested by the body. These figures have been adjusted to reflect that 
reduced availability.'' The comment states that the amount of available 
fat, saturated fat, and polyunsaturated fat would be listed. 
Alternatively, the comment stated that if the Nutrition Facts label 
states ``Fat 0 g'' an asterisk should reference the statement, 
``Contains x grams of olestra, which is not absorbed by the body.''
    In a related comment to the 1996 final rule, P&G stated that the 
amount of olestra per serving should not be included on the label 
because the presence of olestra is already declared in the ingredient 
statement and because the position of olestra within the ingredient 
statement will reflect its predominance based on weight in the food. 
P&G's comment also stated that there is no precedent for requiring the 
declaration of the amount of an ingredient on the food label, and that 
many manufacturers offer consumers access to phone numbers from which 
they could obtain quantitative information about ingredients.
    These comments on the information that should appear on the 
Nutrition Facts panel of olestra-containing foods fall outside the 
scope of this document. As stated in the notice of filing, this 
petition proposed to amend the food additive regulations by removing 
the requirement for the label statement prescribed in Sec.  172.867(e), 
the requirement for which is found only in paragraphs (e)(1) through 
(e)(3).
    FDA notes, however, that the current regulation on ingredient 
labeling (Sec.  101.4) requires food ingredients to be declared by 
their common or usual names in the ingredient statement of the food. 
Accordingly, olestra-containing foods must declare olestra as an 
ingredient of the food. Olestra's placement in the declaration of 
ingredients is determined by its predominance based on weight in the 
food. In addition, Sec.  101.4(e) provides manufacturers with a uniform 
method to voluntarily declare the percentage of each ingredient in 
their product (58 FR 2850 at 2865, January 6, 1993).
    (Comment 40) A comment from CSPI to the current petition stated 
that olestra-containing food should not be allowed to use the phrase 
``fat-free.'' The comment stated that olestra is a fat; therefore, the 
term ``fat-free'' on the label of olestra-containing foods is 
inaccurate. Instead of using the phrase ``fat-free,'' CSPI suggested 
that olestra-containing food could declare ``no calories from fat'' or 
``contains x grams of olestra.'' This type of labeling statement would 
help to differentiate baked snacks from olestra-containing

[[Page 46400]]

snacks. The comment stated that an ounce of baked chips provides an 
ounce of carbohydrate and protein, whereas an ounce of olestra-
containing chips provides only two-thirds to three-fourths an ounce of 
carbohydrate and protein.
    A comment from a potato chip manufacturer to the 1996 final rule 
stated that olestra-containing foods should not be allowed to declare 
``fat-free'' and ``low fat'' because the fat content of olestra-fried 
chips is equal in quantity to that of any standard chip; therefore, the 
comment concluded that the label statement is misleading.
    These comments on the declaration of ``fat-free'' on olestra-
containing foods fall outside the scope of this document. As stated in 
the notice of filing, this petition proposed to amend the food additive 
regulations by removing the requirement for the label statement 
prescribed in Sec.  172.867(e). The requirement for the label statement 
is found only in Sec.  172.867(e)(1) through (e)(3). These comments 
relate to a requirement found in Sec.  172.867(e)(5).
    FDA notes that the agency previously concluded that olestra shall 
not be considered to be a source of fat or calories for purposes of 
nutrition labeling or nutrient content claims because olestra is 
neither a triglyceride nor is it absorbed or metabolized like a fat 
(Sec.  172.867(e)(5)).

I. Appearance of the Label Statement

    (Comment 41) Comments to both the current petition and the 1996 
final rule addressed the appearance of the label statement. Comments 
from individual consumers and CSPI requested that the label statement 
be larger, printed in bold type, and placed on the principal display 
panel of the package to increase its prominence. CSPI stated that many 
of those who used CSPI's telephone line to report reactions did not see 
the label statement prior to consumption, and several comments from 
consumers stated this as well. In its comments to the 1996 final rule, 
CSPI requested that the label statement be placed far enough from the 
edges of the container to provide a flat unobscured surface for the 
wording, that there be sufficient white space around the box to set off 
the wording within the box, that the label statement be black on a 
white background, that the size of the text increase as the package 
size increases, that a prefatory word such as ``Notice'' precede the 
label statement, and that the box around the label statement be 
retained because boxed statements increase the likelihood that 
consumers will read the statement.
    Comments from a trade association to the 1996 final rule stated 
that the olestra label statement should use general food labeling 
typography (as described in Sec. Sec.  101.2, 101.3, and 101.105), like 
that used for labels on products containing mannitol, sorbitol, and 
polydextrose. Frito-Lay argued that the appearance requirements of the 
olestra label should be aligned with those of other substances with 
similar effects and levels of concern. The comment pointed out that 
label statements for food additives that are proven to cause serious 
health problems, such as sulfites (21 CFR 130.9), do not have the 
stringent requirements for labeling prominence that are required of 
olestra, which has been determined to be safe. Comments from P&G and a 
trade association stated that the box around the label statement should 
be eliminated because it increases concern about the safety of the 
product. P&G stated that boxed statements are appropriate only when 
death or very serious illness is a possible outcome of customary or 
usual use.
    As explained previously, FDA has concluded that olestra-containing 
foods should no longer be required to bear the label statement required 
by the 1996 final rule. Therefore, the appearance of the label 
statement is no longer an issue. The label for olestra-containing foods 
will be required to provide information about the added vitamins A, D, 
E, and K through an asterisk, in the list of ingredients, referencing 
the statement ``Dietarily insignificant.'' The prominence and placement 
of the phrase ``Dietarily insignificant'' will follow customary 
practice for other food products (such as Sec. Sec.  101.60, 101.61, 
and 101.62) and will appear prominently and conspicuously as specified 
in Sec.  101.2(c).

J. Labeling for Single-Serving Packages

    (Comment 42) Comments from Frito-Lay and a trade association to the 
1996 final rule stated that single serving packages of olestra-
containing foods should be exempt from the requirement to bear a label 
statement because the small package of such containers is not 
compatible with the label statement, and because the portion contained 
in such packages is so small that the label statement may not disclose 
a material fact. Frito-Lay recommended that instead of the label 
statement required on larger packaging, single-serving packages include 
the statement, ``For information on olestra call 1-800-XXX-XXXX.''
    In contrast, CSPI stated that single-serving packages should be 
required to bear the label statement because studies by P&G show that 
the amount of olestra contained in such packages is sufficient to 
increase the incidence of GI disturbances.
    As explained previously, FDA has concluded that olestra-containing 
foods should no longer be required to bear a label statement that 
informs consumers about the potential GI effects of these products. 
Therefore, whether single-serving containers should be required to bear 
the label statement is no longer an issue. FDA does not believe that 
single serving packages should be exempt from the required labeling of 
added vitamins A, D, E, and K with an asterisk and the phrase 
``Dietarily insignificant'', nor do the comments provide a basis for 
such an exemption.

K. 1995 and 1998 FAC Meetings

    (Comment 43) A comment from CSPI to the current petition criticized 
the 1995 and 1998 FAC meetings held by FDA. CSPI asserted that the 1995 
FAC did not provide objective advice to FDA regarding the approval of 
olestra.\71\ CSPI also stated that the committee did not contain a 
single expert on carotenoids and that 9 of the 17 committee members who 
concluded that olestra meets the safety standard of ``reasonable 
certainty of no harm'' were affiliated with industry.
---------------------------------------------------------------------------

    \71\ In its comment CSPI cites Ref. 36.
---------------------------------------------------------------------------

    CSPI also stated that the conclusions of the 1998 FAC must be 
considered in light of the fact that the committee did not consider 
studies conducted prior to January 30, 1996, including those studies 
that CSPI stated prove that olestra can cause gastrointestinal symptoms 
and reduce serum carotenoid levels. CSPI also pointed out that the 1998 
FAC did not consider the Fecal Parameters Study even though it was 
provided to FDA after the 1995 FAC meeting. CSPI also stated that 
reports of GI symptoms such as diarrhea, cramps, and nausea were 
downplayed at the 1998 FAC because they were not ``unexpected'' 
problems and the committee was asked only to consider whether there 
were any ``unexpected'' problems associated with olestra.
    FDA does not agree that the 1995 FAC provided biased advice. CSPI 
raised this issue previously and FDA responded in the 1996 final rule 
(61 FR 3118 at 3164). As stated in the 1996 final rule, FAC members are 
screened prior to each meeting to determine if they have a conflict of 
interest with the material to be discussed at the meeting. Committee 
members are also expected to provide an objective opinion on the 
information presented. FDA believes that the committee was fairly 
balanced as

[[Page 46401]]

required by the Federal Advisory Committee Act (FACA). FDA also 
believes that there is no basis to conclude that the 10 nutrition 
experts at the FAC meeting were not able to understand the views and 
information presented on carotenoids (61 FR 3118 at 3164).
    As part of the 1996 final rule, FDA announced its intention to 
review and evaluate all data and information bearing on the safety of 
olestra received by the agency within the first 30 months after the 
approval of olestra and to present an evaluation of the data to the 
agency's FAC (Sec.  172.867(f)). Consistent with its obligation, in 
1998 FDA presented to the FAC an evaluation of the data and information 
obtained since the 1996 approval of olestra. The purpose of the 
presentation was to receive advice from the Committee on whether there 
continued to be reasonable certainty that use of olestra is not 
harmful. Specifically, the 1998 FAC was asked to evaluate whether data 
and information obtained since the approval of olestra raised safety 
concerns regarding any GI effects that were not anticipated at the time 
of olestra's approval and whether any newly available data showed that 
consumption of olestra-containing foods had a significant adverse 
health effect due to olestra's interference with absorption of fat-
soluble vitamins or other lipophilic substances.\72\ The committee was 
also asked whether the label statement should be changed in light of 
new data and information. Because the FAC was asked if there were any 
new issues raised since the approval of olestra, the committee was 
asked to consider only the data and information obtained since the 
approval of olestra. Much of the new data focused on the effects of 
``real life'' consumption of olestra-containing foods (i.e., the 
Rechallenge Study, the Acute Consumption Study, and the Home 
Consumption Study). The studies conducted prior to the approval of 
olestra, such as the Fecal Parameters Study, examined the effects of 
olestra when consumed under conditions designed to assess safety and 
were previously considered by FDA in its review of the petition for the 
use of olestra in savory snacks. Although the 1998 FAC did not consider 
the petitioner's Fecal Parameters Study, the committee did consider the 
Stool Composition Study. Like the Fecal Parameters Study, the Stool 
Composition Study was designed to examine olestra's effect on objective 
stool characteristics but tested a higher dose of olestra and collected 
stool samples on a greater number of days than was done in the Fecal 
Parameters Study. The committee also considered FDA's analysis of the 
reports collected through passive surveillance by P&G and CSPI, which 
include reports of GI symptoms such as diarrhea and abdominal pain.\73\ 
Upon review of the data and information received since the 1996 final 
rule, a majority of the FAC concluded that there continues to be 
reasonable certainty of no harm concerning the use of olestra in savory 
snacks.\74\ FDA believes that the data and information considered by 
the 1998 FAC were appropriate for the objective of the meeting, to 
determine whether the data and information obtained since the approval 
and marketing of olestra raise any issue not anticipated at the time of 
approval.
---------------------------------------------------------------------------

    \72\ Transcript, vol. 1, pp. 22-25.
    \73\ Transcript, vol. 1, pp. 258-270.
    \74\ Transcript, vol. 3, pp. 101-174.
---------------------------------------------------------------------------

VI. Summary

    In its petition, P&G requested that FDA amend the food additive 
regulations in Sec.  172.867 Olestra by removing the requirement for 
the label statement prescribed in Sec.  172.867(e). Based on its 
analysis of data and information in the petition, as well as data and 
information in FAP 7A3997 (which resulted in the establishment of Sec.  
172.867(e)), FDA has concluded that olestra-containing foods should no 
longer be required to bear a label statement informing consumers of 
possible GI symptoms from consumption of olestra. FDA also has 
concluded that olestra-containing foods should no longer be required to 
bear a label statement informing consumers of possible effects of 
olestra on the absorption of some vitamins and other nutrients. 
Finally, FDA has concluded that olestra-containing foods should no 
longer be required to bear a label statement informing consumers that 
vitamins A, D, E and K have been added. Instead, the listing of the 
vitamins in the ingredient statement of olestra-containing foods will 
now be followed by an asterisk that is linked to the statement 
``Dietarily insignificant.''

VII. Environmental Impact

    The agency has determined under 21 CFR 25.30(k) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VIII. Inspection of Documents

    In accordance with Sec.  171.1(h), the petition and the documents 
that FDA considered and relied upon in reaching its decision to approve 
the petition are available for inspection at the Center for Food Safety 
and Applied Nutrition (see ADDRESSES) by appointment with the 
information contact person. As provided in Sec.  171.1(h), the agency 
will delete from the documents any materials that are not available for 
public disclosure before making the documents available for inspection.
    Additionally, a copy of P&G's December 1999 petition and additional 
supporting material that P&G supplied are publically available at the 
Division of Dockets Management (Docket No. 00F-0792.

IX. Objections

    Any person who will be adversely affected by this regulation may 
file with the Division of Dockets Management (see ADDRESSES) written or 
electronic objections by (see DATES). Each objection shall be 
separately numbered, and each numbered objection shall specify with 
particularity the provisions of the regulation to which objection is 
made and the grounds for the objection. Each numbered objection on 
which a hearing is requested shall specifically so state. Failure to 
request a hearing for any particular objection shall constitute a 
waiver of the right to a hearing on that objection. Each numbered 
objection for which a hearing is requested shall include a detailed 
description and analysis of the specific factual information intended 
to be presented in support of the objection in the event that a hearing 
is held. Failure to include such a description and analysis for any 
particular objection shall constitute a waiver of the right to a 
hearing on the objection. Three copies of all documents shall be 
submitted and shall be identified with the docket number found in 
brackets in the heading of this document. Any objections received in 
response to the regulation may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

X. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m. Monday through Friday.

    1. Transcript of the meeting of the Food Advisory Committee 
(vols. 1-3), Reston, VA, June 15 through 17, 1998.
    2. Memorandum from K. C. Klontz, FDA to M. Ditto, FDA, February 
13, 1998.

[[Page 46402]]

    3. Memorandum from A. S. Levy, FDA to H. Thorsheim, FDA, August 
20, 1996.
    4. Memorandum from D. A. Street, FDA to M. Ditto, FDA, October 
23, 2000.
    5. Memorandum from K. C. Klontz, FDA to M. Ditto, FDA, February 
23, 2000.
    6. Memorandum K. C. Klontz and E. F. Barker, FDA to H. 
Thorsheim, FDA, March 26, 1997.
    7. Memorandum K. C. Klontz, FDA to H. Thorsheim, FDA, August 8, 
1996.
    8. Zorich, N. L., D. Biedermann, K. A. Riccardi, et al., 
``Randomized, Double-Blind, Placebo-Controlled, Consumer Rechallenge 
Test of Olean Salted Snacks,'' Regulatory Toxicology and 
Pharmacology, 26:200-209, 1997.
    9. Zorich, N. L., D. Biedermann, K. A. Riccardi, et al., 
``Follow-Up to the Study: A Randomized, Double-Blind, Placebo-
Controlled Consumer Rechallenge Test of Olean Salted Snacks,'' 
Regulatory Toxicology and Pharmacology, 27:2, 1998.
    10. Memorandum from K. C. Klontz, FDA to M. Ditto, FDA, May 25, 
2000.
    11. Memorandum from K. C. Klontz, FDA, to M. Ditto, FDA, April 
13, 1998.
    12. Cheskin, L. J., R. Miday, N. Zorich, et al., 
``Gastrointestinal Symptoms Following Consumption of Olestra or 
Regular Triglyceride Potato Chips: a Controlled Comparison,'' 
Journal of the American Medical Association, 279:150-152, 1998.
    13. Memorandum from P. V. McCarthy, FDA, to M. Ditto, FDA, 
August 26, 1998.
    14. Sandler, R. S., N. L. Zorich, T. G. Filloon, et al., 
``Gastrointestinal Symptoms in 3181 Volunteers Ingesting Snack Foods 
Containing Olestra or Triglycerides. A 6-Week Randomized, Placebo-
Controlled Trial,'' Annals of Internal Medicine, 130:253-261, 1999.
    15. Memorandum from S. J. Chirtel, FDA to B. Timbo, FDA, July 
16, 1998.
    16. Memorandum from C. Barton, FDA to B. Timbo, FDA, May 7, 
1999.
    17. Memorandum from C. Barton, FDA to M. Ditto, FDA, May 7, 
1999.
    18. Memorandum from H. E. Gallo-Torres, FDA, June 5, 1998.
    19. Jacobson, M. F., M. A. Brown, and E. B. Whorton, 
``Gastrointestinal Symptoms Following Olestra Consumption,'' Journal 
of the American Medical Association, 280:325-326, 1998.
    20. Jacobson, M. F., ``Olestra Snacks Compared with Regular 
Snacks,'' Annals of Internal Medicine, 131:866, 1999.
    21. Memorandum from C. Barton, and S. Chirtel, FDA to M. Ditto, 
FDA, March 27, 2003.
    22. Memorandum K. C. Klontz, FDA to H. Thorsheim, FDA, December 
26, 1995.
    23. Kristal, A. R., R. E. Patterson, M. L. Neuhouser, et al., 
``Olestra Postmarketing Surveillance Study: Design and Baseline 
Results from the Sentinel Site,'' Journal of the American Dietetic 
Association, 98: 1290-1296, 1998.
    24. Memorandum from T.G. Wilcox, FDA to M. Ditto, FDA, November 
22, 2000.
    25. Cooper, D. A., A. L. Eldridge, and J. C. Peters, ``Dietary 
Carotenoids and Lung Cancer: a Review of Recent Research,'' 
Nutrition Reviews, 57:133-145, 1999.
    26. Cooper, D. A., A. L. Eldridge, and J. C. Peters, ``Dietary 
Carotenoids and Certain Cancers, Heart Disease, and Age-Related 
Macular Degeneration: a Review of Recent Research,'' Nutrition 
Reviews, 57:201-214, 1999.
    27. Institute of Medicine (U.S.), Panel on Dietary Antioxidants 
and Related Compounds, ``Beta-Carotene and Other Carotenoids,'' 
Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and 
Carotenoids: A Report of the Panel on Dietary Antioxidants and 
Related Compounds, Subcommittees on Upper Reference Levels of 
Nutrients and Interpretation and Uses of Dietary Reference Intakes, 
and the Standing Committee on the Scientific Evaluation of Dietary 
Reference Intakes, Food and Nutrition Board, Institute of Medicine, 
pp. 325-382, Washington, DC: National Academy Press, 2000.
    28. Memorandum of Meeting, August 31, 2000.
    29. Letter from A. Rulis, FDA, to J. McLaughlin, NEI, September 
15, 2000.
    30. Letter from J. McLaughlin, NEI, to A. Rulis, FDA, October 
17, 2000.
    31. Age-Related Eye Disease Study Research Group, ``A 
Randomized, Placebo-Controlled, Clinical Trial of High-Dose 
Supplementation with Vitamins C and E, Beta Carotene, and Zinc for 
Age-Related Macular Degeneration and Vision Loss,'' Archives of 
Ophthalmology, 119:1417-1436, 2001.
    32. Memorandum from A. S. Levy, FDA to H. Thorsheim, FDA, July 
30, 1996.
    33. Memorandum from A. S. Levy, FDA to M. Ditto, FDA, November 
16, 2000.
    34. Kelly, S. M., M. Shorthouse, J. C. Cotterell, et al., ``A 3-
Month, Double-Blind, Controlled Trial of Feeding with Sucrose 
Polyester in Human Volunteers,'' British Journal of Nutrition, 
80:41-49, 1998.
    35. Memorandum from R. Pertel, FDA to N. Beru, FDA, September 6, 
1995.
    36. Blackburn, H., ``Sounding Board: Olestra and the FDA,'' New 
England Journal of Medicine, 334:984-986, 1996.
    37. Westrate, J. A. and K. H. van het Hof, ``Sucrose Polyester 
and Plasma Carotenoid Concentrations in Healthy Subjects,'' American 
Journal of Clinical Nutrition, 62:591-597, 1995.
    38. Lawton, C. L., ``Regulation of Energy and Fat Intakes and 
Body Weight: the Role of Fat Substitutes,'' British Journal of 
Nutrition, 80:3-4, 1998.
    39. Giovannucci, E., ``Tomatoes, Tomato-Based Products, 
Lycopene, and Cancer: Review of the Epidemiologic Literature,'' 
Journal of the National Cancer Institute, 91:317-331, 1999.
    40. Chasan-Taber, L., W. C. Willet, J. M. Seddon, et al., ``A 
Prospective Study of Carotenoid and Vitamin A Intakes and Risk of 
Cataract Extraction in U.S. Women,'' American Journal of Clinical 
Nutrition, 70:509-516, 1999.
    41. Brown, L., E. B. Rimm, J. M. Seddon, et al., ``A Prospective 
Study of Carotenoid Intake and Risk of Cataract Extraction in U.S. 
Men,'' American Journal of Clinical Nutrition, 70:517-524, 1999.
    42. Balasekaran, R., J. L. Porter, C. A. Santa Ana, et al., 
``Positive Results on Tests for Steatorrhea in Persons Consuming 
Olestra Potato Chips,'' Annals of Internal Medicine, 132:279-282, 
2000.
    43. Burks, A. W., L. Christie, K. A. Althage, et al., 
``Randomized, Double-Blind, Placebo-Controlled, Food Allergy 
Challenge to Olestra Snacks,'' Regulatory Toxicology and 
Pharmacology, 34: 178-181, 2001.

List of Subjects in 21 CFR Part 172

    Food additives, Reporting and recordkeeping requirements.


0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
172 is amended as follows:

PART 172--FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR 
HUMAN CONSUMPTION

0
1. The authority citation for 21 CFR part 172 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 341, 342, 348, 371, 379e.

0
2. Section 172.867 is amended by revising paragraph (e) to read as 
follows:


Sec.  172.867  Olestra.

* * * * *
    (e)(1) Vitamins A, D, E, and K present in foods as a result of the 
requirement in paragraph (d) of this section shall be declared in the 
listing of ingredients. Such vitamins shall not be considered in 
determining nutrient content for the nutritional label or for any 
nutrient claims, express or implied.
    (i) An asterisk shall follow vitamins A, D, E, and K in the listing 
of ingredients;
    (ii) The asterisk shall appear as a superscript following each 
vitamin;
    (iii) Immediately following the ingredient list an asterisk and 
statement, ``Dietarily insignificant'' shall appear prominently and 
conspicuously as specified in Sec.  101.2(c) of this chapter;
    (2) Olestra shall not be considered as a source of fat or calories 
for purposes of Sec. Sec.  101.9 and 101.13 of this chapter.
* * * * *

    Dated: July 17, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-19508 Filed 8-1-03; 4:00 pm]
BILLING CODE 4160-01-P