98-4074. Food Labeling: Health Claims; Soluble Fiber From Certain Foods and Coronary Heart Disease  

  • [Federal Register Volume 63, Number 32 (Wednesday, February 18, 1998)]
    [Rules and Regulations]
    [Pages 8103-8121]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 98-4074]
    
    
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    DEPARTMENT OF HEALTH AND HUMAN SERVICES
    
    Food and Drug Administration
    
    21 CFR Part 101
    
    [Docket No. 96P-0338]
    
    
    Food Labeling: Health Claims; Soluble Fiber From Certain Foods 
    and Coronary Heart Disease
    
    AGENCY: Food and Drug Administration, HHS.
    
    ACTION: Final rule.
    
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    SUMMARY: The Food and Drug Administration (FDA) is announcing its 
    decision to authorize the use, on food labels and in food labeling, of 
    health claims on the association between soluble fiber from psyllium 
    seed husk and reduced risk of coronary heart disease (CHD). Based on 
    its review of evidence submitted with comments to the proposal, as well 
    as evidence described in the proposal, the agency has concluded that 
    soluble fiber from psyllium seed husk, similar to beta ()-
    glucan soluble fiber from whole oats, when included as part of a diet 
    low in saturated fat and cholesterol, may reduce the risk of CHD by 
    lowering blood cholesterol levels. The agency has concluded, based on 
    the totality of publicly available scientific evidence, that there is 
    significant scientific agreement among qualified experts to support the 
    relationship between soluble fiber in psyllium seed husk and CHD. 
    Therefore, the agency has decided to amend the regulation that 
    authorized a health claim on soluble fiber from whole oats and the risk 
    of CHD to include soluble fiber from psyllium seed husk. FDA has 
    determined that label statements alerting consumers to the need to 
    consume adequate amounts of liquids with products containing dry or 
    incompletely hydrated psyllium will be required on products bearing the 
    health claim. FDA is announcing this action in response to a petition 
    filed by the Kellogg Co. (the petitioner).
    
    DATES: This regulation is effective February 18, 1998. The Director of 
    the Office of the Federal Register approves of the incorporation by 
    reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of 
    certain publications in 21 CFR 101.81(c)(2)(ii)(B), effective February 
    18, 1998.
    
    FOR FURTHER INFORMATION CONTACT: Virginia L. Wilkening, Center for Food 
    Safety and Applied Nutrition (HFS-165), Food and Drug Administration, 
    200 C St. SW., Washington, DC 20204, 202-205-5483.
    
    SUPPLEMENTARY INFORMATION:
    
    I. Background
    
        On November 8, 1990, the Nutrition Labeling and Education Act of 
    1990 (the 1990 amendments) (Pub. L. 101-535) was signed into law. This 
    new law amended the Federal Food, Drug, and Cosmetic Act (the act) in a 
    number of important ways. One of the most notable aspects of the 1990 
    amendments was that they confirmed FDA's authority to regulate health 
    claims on food labels and in food labeling. FDA published final rules 
    implementing the 1990 amendments on January 6, 1993 (58 FR 2478). In 
    those final rules, FDA adopted Sec. 101.14 (21 CFR 101.14), which sets 
    out the rules for the authorization and use of health claims. The 
    agency also adopted Sec. 101.70 (21 CFR 101.70), which establishes a 
    process for petitioning the agency to authorize health claims about a 
    substance-disease relationship and sets out the types of information 
    that any such petition must include.
        In addition, FDA conducted an extensive review of the evidence on 
    the 10 substance disease relationships listed in the 1990 amendments. 
    As a result of its review, FDA authorized a health claim in Sec. 101.77 
    (21 CFR 101.77) on the association between diets low in saturated fat 
    and cholesterol and high in vegetables, fruits, and grain products that 
    contain soluble fiber and a reduced risk of heart disease (58 FR 2552, 
    January 6, 1993). In that rulemaking, FDA reviewed the evidence 
    relating dietary fiber to heart disease and concluded that it was 
    difficult to determine the relationship because dietary fiber comprises 
    a diverse group of chemical substances that may be associated with 
    different physiological functions (58 FR 2552 at 2572). Chemically and 
    physiologically, cellulose, lignin, hemicellulose, pectin, and alginate 
    (all relatively purified fiber types) behave differently from one 
    another. Likewise, wheat bran, oat bran, and rice bran are not similar 
    in composition. The agency noted that the available evidence made it 
    difficult to correlate the role of specific fiber components to health 
    effects.
        However, in its final rule, FDA noted that hypocholesterolemic 
    properties may be documented for specific food fibers (58 FR 2552 at 
    2567). Further, the agency stated that if manufacturers could document, 
    through appropriate studies, that dietary consumption of the soluble 
    fiber in their particular food has the effect of lowering low density 
    lipoprotein (LDL)-cholesterol, and has no adverse effects on other 
    heart disease risk factors (e.g., high density lipoprotein (HDL)-
    cholesterol), they should petition for a health claim for their 
    particular product.
        In accordance with the petition procedure in Sec. 101.70, FDA 
    published a final rule on the relationship between soluble fiber from 
    whole oats and reduced risk of heart disease (the soluble fiber from 
    whole oats final rule), Sec. 101.81 (21 CFR 101.81) (62 FR 3584, 
    January 23, 1997 and modified at 62 FR 15343, March 31, 1997). In that 
    document, the agency concluded that, based on the totality of publicly 
    available scientific evidence, there is significant scientific 
    agreement among qualified experts to support the relationship between 
    soluble fiber in whole oats and reduced risk of CHD. FDA also concluded 
    that the type of soluble fiber in whole oats, -glucan soluble 
    fiber, is the primary component responsible for the lowering of blood 
    total- and LDL-cholesterol associated with consumption of whole oat 
    products when part of a diet low in saturated fat and cholesterol. The 
    rule specified the chemical nature of the specific fiber and methods 
    for measuring its presence in foods.
        In the soluble fiber from whole oats final rule, the agency 
    acknowledged the likelihood that consumption of -glucan 
    soluble fiber from sources other than whole oats, as well as soluble 
    fiber from other sources, will affect blood lipid levels and thus the 
    risk of heart disease (62 FR 3584 at 3587). At that time, FDA 
    considered structuring the final rule as an umbrella regulation 
    authorizing the use of a claim for ``soluble fiber from certain foods'' 
    and risk of CHD. Such action would have allowed flexibility in 
    expanding the claim to other specific food sources of soluble fiber 
    when
    
    [[Page 8104]]
    
    consumption of those foods has been demonstrated to help reduce risk of 
    heart disease. However, the agency concluded that it was premature to 
    do so inasmuch as FDA had not reviewed the totality of evidence on 
    other, nonwhole oat sources of soluble fiber (62 FR 3584 at 3588). 
    Instead, the agency stated that because soluble fiber is a family of 
    very heterogeneous substances that vary greatly in their effect on risk 
    of CHD, a case-by-case approach is necessary as documentation is 
    developed through appropriate studies that a soluble fiber product has 
    an effect on blood total- and LDL-cholesterol levels and can therefore 
    be useful in reducing risk of CHD. To this end, FDA structured 
    Sec. 101.81 in such a way that, while the regulation covered -
    glucan soluble fiber from whole oats, it could easily be amended as 
    evidence becomes available to support the use of the claim for other 
    sources of soluble fiber.
        In the soluble fiber from whole oats final rule, FDA emphasized the 
    importance of the dietary component of the health claim, i.e., the 
    necessity for the whole oat product to be consumed as part of a low 
    saturated fat, low cholesterol diet, for a complete understanding of 
    the claim (62 FR 3684 at 3594). FDA stated that diets low in saturated 
    fat and cholesterol are considered by expert groups to be the most 
    effective dietary means of reducing heart disease risk, and that, while 
    soluble fiber from whole oats could contribute to this effect, its role 
    is generally recognized as being of smaller magnitude.
        In the Federal Register of May 22, 1997 (62 FR 28234), and in 
    response to a petition filed under Sec. 101.70, the agency proposed to 
    amend Sec. 101.81 by adding psyllium seed husk as an additional source 
    of soluble fiber, thereby providing for health claims on the 
    association between soluble fiber from psyllium seed husk and reduced 
    risk of CHD (the psyllium husk proposed rule). In this proposed rule, 
    FDA considered the relevant scientific studies and data presented in 
    the petition as part of its review of the scientific literature on 
    soluble fiber from psyllium seed husk and heart disease. The agency 
    summarized this evidence in the proposed rule (62 FR 28234).
        The psyllium husk proposed rule included qualifying criteria for 
    the purpose of identifying psyllium-containing foods eligible to bear 
    the proposed health claim. The proposal also specified mandatory 
    content and label information for health claim statements and provided 
    model health claims.
        Section 101.81(c)(2)(ii) of the soluble fiber from whole oats 
    health claim regulation lists the sources of -glucan soluble 
    fiber for which FDA has evaluated data pertaining to effects on blood 
    cholesterol levels and has concluded that significant scientific 
    agreement exists regarding a relationship between soluble fiber in 
    whole oats and the risk of CHD. In the psyllium husk proposed rule, FDA 
    proposed to add new Sec. 101.81(c)(2)(ii)(B) to specify psyllium husk 
    as a source of soluble fiber eligible to be the subject of this claim. 
    Proposed Sec. 101.81(c)(2)(ii)(B)(1) identifies psyllium husk as the 
    dried seed coat (epidermis) of the seed of Plantago ovata, known as 
    blond or Indian psyllium, P. indica, or P. psyllium, and specifies that 
    the purity of the psyllium husk shall be no less than 95 percent, such 
    that it has 3 percent or less protein content, 4.5 percent or less of 
    light extraneous matter, and 0.5 percent or less of heavy extraneous 
    matter, but in no case may the combined extraneous matter exceed 4.9 
    percent, as determined by U.S. Pharmacopeia (USP) methods.
        In its evaluation of the scientific evidence for a relationship 
    between consumption of soluble fiber from psyllium seed husk and blood 
    total- and LDL-cholesterol levels, the agency found no reliable data to 
    establish a dose-response for this relationship. However, the agency 
    did find that in placebo-controlled studies that tested an intake of 
    10.2 grams (g) of psyllium seed husk per day as a part of a diet low in 
    saturated fat and cholesterol, there were consistently significant 
    effects of psyllium husk on blood total- and LDL-cholesterol levels. 
    Therefore, the agency proposed to base the qualifying level of soluble 
    fiber from psyllium seed husk on a total daily intake of 10.2 g husk 
    (about 7 g of soluble fiber), as suggested by the petitioner. 
    Therefore, the proposed qualifying criterion in 
    Sec. 101.81(c)(2)(iii)(A)(2) was that the food provide at least 1.7 g 
    of soluble fiber from psyllium seed husk per reference amount 
    customarily consumed (RACC) (i.e., 7 g divided by 4 eating occasions 
    per day). The psyllium husk proposed rule also stated that if a 
    manufacturer can demonstrate that a diet low in saturated fat and 
    cholesterol that includes a blend of the eligible sources of soluble 
    fiber listed in Sec. 101.81(c)(2)(ii) has an effect on the risk of 
    heart disease, the manufacturer should petition to amend Sec. 101.81 
    further.
        To reflect the agency's tentative decision to broaden Sec. 101.81 
    to include soluble fiber from psyllium seed husk, the agency proposed 
    to modify the section heading in Sec. 101.81 from ``Soluble fiber from 
    whole oats and risk of coronary heart disease'' to ``Soluble fiber from 
    certain foods and risk of coronary heart disease.'' Accordingly, the 
    agency also proposed to revise the statement ``soluble fiber from whole 
    oats'' to either ``soluble fiber from certain foods'' or ``soluble 
    fiber from the eligible food sources from paragraph (c)(2)(ii) of this 
    section'' where appropriate in Sec. 101.81. The agency did not propose 
    to modify the model claims.
    
    II. Summary of Comments and the Agency's Responses
    
        In response to the psyllium husk proposed rule, the agency received 
    19 letters, each containing one or more comments, from professional 
    organizations, industry, consumer groups, health care professionals, 
    and research scientists.
        Approximately one-half of the comments that the agency received 
    agreed with one or more provisions of the psyllium husk proposed rule 
    without providing grounds for this support other than those provided by 
    FDA in the preamble to the psyllium husk proposed rule. A few of these 
    comments also requested modification of one or more provisions of the 
    proposed rule. Some comments provided additional data on the 
    relationship between psyllium husk soluble fiber and CHD. Some of the 
    comments that disagreed with the proposed rule provided specific 
    support for their positions. The agency has summarized and addressed 
    the relevant issues raised in all comments in the sections of this 
    document that follow.
    
    A. Food Substance Associated With Reduced Risk of CHD
    
        Health claims have two essential elements: A food substance and a 
    disease or health-related condition (Sec. 101.14). The agency proposed 
    to authorize a health claim on the relationship between consumption of 
    soluble fiber from psyllium husk, as part of a diet low in saturated 
    fat and cholesterol, and reduced risk of CHD. Further, the agency 
    proposed to amend the authorized claim for soluble fiber from whole 
    oats and CHD (Sec. 101.81) to include soluble fiber from psyllium husk 
    and to broaden the subject of the claim to ``soluble fiber from certain 
    foods'' and risk of CHD (62 FR 28234 at 28239).
    1. Terminology
    (Comment 1)
        Comments received in response to the proposed rule used the term 
    ``psyllium''
    
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    interchangeably with the terms ``psyllium seed husk'' and ``psyllium 
    husk.'' The agency also noticed that a few comments used the term 
    ``psyllium'' when referring to the soluble fiber component of the 
    psyllium husk. Therefore, the agency finds it important to clarify the 
    terms that may be used in referring to the substance that is the 
    subject of this claim as well as the common or usual name of the 
    product that should be used in ingredient statements.
        The substance that is the subject of this claim is soluble fiber of 
    the psyllium husk, i.e., the seed coat that has been removed from the 
    psyllium seed. It is the seed husk, rather than the seed, that is the 
    source of soluble dietary fiber. The purity specifications suggested by 
    the petitioner and adopted in proposed Sec. 101.81(c)(2)(ii)(B)(1) 
    refer to the extent to which psyllium husk has been separated from 
    residual seed components.
        The agency notes that in the ingredient list of the petitioner's 
    psyllium husk-containing cereal the substance is declared as ``psyllium 
    seed husk'' (Ref. 1). The agency also notes that in the USP National 
    Formulary this substance is referred to as ``psyllium husk'' (Ref. 2). 
    The agency therefore considers both ``psyllium seed husk'' and 
    ``psyllium husk'' to be common or usual names for the soluble dietary 
    fiber source that is the subject of this rule. In the psyllium husk 
    proposed rule, the agency used the term ``psyllium'' synonymously with 
    the term ``psyllium husk'' (62 FR 28234 at 28237). Upon further 
    consideration, the agency concludes that the term ``psyllium'' is not 
    sufficiently descriptive of the substance of this claim because this 
    term is likely to be construed as inclusive of the psyllium seed. The 
    psyllium seed includes nutrients and allergenic proteins that are not 
    components of psyllium husk. The psyllium husk purity specifications of 
    Sec. 101.81(c)(2)(ii)(B)(1) make the presence of psyllium seed in a 
    food a disqualifying criterion for foods eligible to bear the claim.
        In this final rule, the agency is clarifying under 
    Sec. 101.81(c)(2) that the proper terms for the soluble fiber source 
    which is the substance of this rule are ``psyllium husk'' or ``psyllium 
    seed husk.'' Therefore, Sec. 101.81 (c)(2)(ii)(B)(1) is revised to read 
    ``psyllium seed husk, also known as psyllium husk, shall have a purity 
    of * * *.'' Section 101.81 (c)(2)(ii)(B)(1), (c)(2)(ii)(B)(2), and 
    (c)(2)(iii)(A)(2) are revised to read ``psyllium husk'' where the term 
    ``psyllium'' had been used in the proposed rule.
    2. Eligibility of Psyllium Seed Husk
    (Comment 2)
        Some comments stated that psyllium husk is not a food and is not 
    consumed by itself. The comments stated that psyllium husk is an 
    ingredient or additive and, therefore, should not be eligible for a 
    health claim. One comment expressed concern that a health claim on a 
    food additive will put more reliance on food fortification or 
    supplementation as a strategy to improve health. The comment asserted 
    that the psyllium proposal represents a public policy shift that may 
    result in diverting attention from the importance of a varied selection 
    of foods.
        FDA disagrees with comments that psyllium husk, as a food 
    ingredient, is not an appropriate substance for consideration of a 
    health claim. As discussed in the final rule implementing the 1990 
    amendments on the use of health claims (58 FR 2478 at 2480, January 6, 
    1993), a broad range of substances are potentially subject to 
    regulation under section 403 (r)(1)(B) of the act (21 U.S.C. 
    343(r)(1)(B)). Section 101.14(a)(2) was written to reflect this broad 
    coverage. Under the general requirements for health claims, the 
    substance that is the subject of the health claim can be either a 
    specific food or a component of food (Sec. 101.14(a)(2)). Moreover, the 
    fact that a substance may be a ``food additive,'' within the meaning of 
    that term in 21 CFR 170.3(g), does not preclude it from also being a 
    ``substance'' under Sec. 101.14(a)(2). Although psyllium seed husk is 
    not consumed as a single food, it is a consumable portion of a seed 
    grain that is, or could be, used as a component of foods (e.g., cereal, 
    pasta, cookies, breakfast bars) and is a rich source of soluble fiber. 
    As such, psyllium seed husk is a ``substance'' within the meaning of 
    Sec. 101.14(a)(2) and thus eligible for consideration of a health 
    claim.
        The agency also disagrees with the comment that the proposed health 
    claim represents a public policy shift in diverting attention from the 
    importance of a varied selection of foods by placing more reliance on 
    food fortification or supplementation to achieve public health goals. 
    The establishment of a health claim for soluble fiber from psyllium 
    husk and CHD, when viewed in conjunction with existing health claims 
    for fruits, vegetables, and grain products and CHD and for soluble 
    fiber from whole oats and CHD, emphasizes an important role (i.e., 
    possible reduced risk of CHD) of an even wider variety of food 
    selections. It is important to note that the concept of formulating a 
    food product with psyllium seed husk is no different than formulating a 
    product with oat bran (another food ingredient supplying soluble fiber 
    that is the subject of an authorized health claim). As with oat bran, 
    the inclusion of psyllium husk in a food would be based on its basic 
    functional properties in addition to its nutritional contribution or 
    potential health benefit. The decision to include such an ingredient in 
    a food would be considered food product development, not fortification. 
    Therefore, the agency disagrees that the approval of this health claim 
    represents a public policy shift on food fortification.
    
    B. Updated Review of Scientific Evidence and Issues Related to the 
    Evidence
    
        Under Sec. 101.14(c), FDA will issue a regulation authorizing a 
    health claim only when it determines, based on the totality of publicly 
    available scientific evidence, that there is significant scientific 
    agreement that the claim is supported by such evidence. In its review 
    of the psyllium petition, the agency completed a comprehensive review 
    (see Ref. 7) of 21 human studies (Refs. 8 through 28) (62 FR 28234 at 
    28237). Of these, it gave particular weight to 7 studies (Refs. 13, 14, 
    15, 18, 22, 23, and 28) that were well designed and controlled and that 
    reported intakes of dietary saturated fat and cholesterol.
    1. Data Submitted With Comments
    (Comment 3)
        One comment to the psyllium husk proposed rule noted that FDA 
    excluded from comprehensive review three studies (Ref. 12, 17, and 25) 
    because they lacked evidence that the study subjects were compliant 
    with a low saturated fat and cholesterol diet (i.e., the American Heart 
    Association ``Step 1'' diet). This comment submitted reports of 
    subsequent diet analyses of these studies indicating that study 
    subjects were compliant with the Step 1 diet (see Docket 96P-0338, C8). 
    This comment also noted that two unpublished studies included in the 
    psyllium petition have since been published or submitted for 
    publication (Refs. 12 and 25).
        Another comment submitted five recently published studies for 
    consideration (Refs. 29 through 33) and three studies for 
    reconsideration (Refs. 14, 28, and 34). The latter were recently 
    published revisions of material submitted in the psyllium petition. The 
    comment stated that the published report by Jenkins et al. (Ref. 28) 
    contains additional data not presented in the
    
    [[Page 8106]]
    
    unpublished report submitted with the petition.
        FDA, in reviewing the supplemental data for Refs. 12, 17, and 25, 
    concluded that this information shows the subjects of these three 
    studies were compliant with the dietary protocol and made no 
    significant changes to their diets throughout the duration of the 
    treatment period. Therefore, these studies have been added to the seven 
    studies to which the agency gave particular weight in evaluating the 
    relationship of soluble fiber from psyllium husk and CHD risk in the 
    psyllium husk proposed rule. These studies are summarized in Table 1 of 
    this document. The results of these three additional studies support 
    the relationship between consumption of soluble fiber from psyllium 
    seed husk and reduced risk of heart disease.
        The agency also reviewed the published version of the study by 
    Jenkins et al. (Ref. 28) that was submitted in comments and has 
    summarized this study accordingly in Table 1 of this document. The 
    investigators evaluated the effect on serum lipid levels of two Step 2 
    metabolic diets that provided either 6 or 12 percent of energy from 
    monounsaturated fat (MUFA), approximately 60 g per day (/d) total 
    dietary fiber, and psyllium seed husk-containing cereal (mean intake of 
    11 g/d of psyllium seed husk) or wheat bran. The results showed 
    significantly lower total- and LDL-cholesterol levels in the psyllium 
    husk-supplemented groups compared to the control group at both MUFA 
    levels. The saturated fat intake during the two study periods was very 
    low (less than 6 percent of energy).
        The agency did not conduct an in-depth review of five of the 
    studies submitted with comments. The study by Jensen and co-workers 
    (Ref. 33) does not meet the agency's criteria for study selection (62 
    FR 28234 at 28237) because the authors evaluated the usefulness of a 
    soluble fiber mixture (containing psyllium, pectin, guar gum, and 
    locust bean gum) in the long-term management of hypercholesterolemia. 
    The results of this study do not allow an evaluation of the effects of 
    soluble fiber from psyllium seed husk alone.
        The experimental design of the study by Ganji and Kies (Ref. 32) 
    did not meet the agency's criteria for comprehensive review. In the 
    psyllium proposal, the agency stated that in evaluating a study, it 
    considered whether the intervention studies had been of long enough 
    duration to reasonably ensure stabilization of blood lipid levels 
    (i.e., greater than or equal to 3 weeks duration) (62 FR 28234 at 
    28237). In this study, diets were varied in four 7-day treatment 
    periods with no time between treatment periods. With this study design, 
    it cannot be determined whether the subjects' blood lipids had 
    stabilized to each diet or that there were no carryover effects from 
    one treatment period to another. Neither did the study design have an 
    adequate pre-intervention baseline period to ensure blood lipids had 
    stabilized to the base diet.
        The other three studies submitted in comments that were not 
    reviewed indepth were animal studies (Refs. 29 through 31). Animal 
    studies are useful in studying mechanisms of action. However, the 
    agency relied primarily on the clinical studies in this rule. Such an 
    approach is consistent with that taken by the agency in its evaluation 
    of the relationship between soluble fiber from whole oats and risk of 
    CHD.
        A meta-analysis (Ref. 34) was conducted to determine the effect of 
    psyllium seed husk-containing cereal products on serum lipid levels in 
    hypercholesterolemic subjects and to estimate the magnitude of the 
    effect among 404 subjects with mild to moderate hypercholesterolemia 
    (total-cholesterol of about 200 to 300 milligrams per deciliter (mg/dL) 
    who followed a low fat diet. In its review of the evidence submitted in 
    the psyllium petition, the agency reviewed 6 of the 11 studies (Refs. 
    11, 13, 22 through 24, and 28) included in the meta-analysis (see 
    tables in Ref. 7). The remaining studies used in the meta-analysis did 
    not meet the agency's criteria for study selection (62 FR 28234 at 
    28237). The conclusion of the meta-analysis report was that 
    hypercholesterolemic subjects who consumed the psyllium seed husk-
    containing cereal had significantly lower total-cholesterol (about 5 
    percent) and LDL-cholesterol (about 9 percent) compared with those 
    subjects who consumed the control cereal (Ref. 34).
    2. Totality of the Data on Soluble Fiber from Psyllium Seed Husk and 
    CHD
    (Comment 4)
        One comment stated that there was considerably more scientific data 
    on psyllium seed husk presented in the petition than that reviewed by 
    the agency. The comment noted that results of 56 studies were included 
    in the psyllium petition. The comment expressed concern that the agency 
    failed to consider studies published prior to 1988 and some additional 
    evidence made available since 1988, noting that studies with soluble 
    fiber mixtures, studies with treatment periods that were less than 3 
    weeks in duration, and abstracts were not selected for comprehensive 
    review. The comment stated that the agency began its review of the 
    scientific evidence by first considering the conclusions of the Surgeon 
    General's report and the Food and Nutrition Board/National Academy of 
    Sciences (FNB/NAS) report (Refs. 3 and 4) and then considered the 
    evidence that was made available since 1988. The comment explained that 
    neither the Surgeon General's report nor the FNB/NAS report reviewed 
    the evidence on psyllium up to 1988; therefore, the agency improperly 
    ignored a significant portion of the scientific evidence provided in 
    the petition (see Ref. 35, Table 3, pages 30 and 31). Another comment 
    noted that among the 56 studies submitted in the psyllium petition (see 
    Ref. 35), the results of only three failed to demonstrate that 
    consumption of psyllium-containing foods was associated with risk of 
    CHD through a reduction in serum cholesterol. The comment stated that 
    the totality of evidence on psyllium husk that was submitted in the 
    petition includes data on children and the elderly.
        Some comments stated that it is premature to authorize a claim on 
    psyllium seed husk and risk of CHD because of a lack of significant 
    scientific agreement on this nutrient/disease relationship. Some of 
    these comments stated that the decision to propose this health claim is 
    based on evidence from a limited number of studies that overall covered 
    a small number of subjects, of which women were underrepresented, and 
    on the absence of data on certain subpopulations (children and the 
    elderly).
        The agency agrees with the comment that the Surgeon General's 
    report (Ref. 3) and the FNB/NAS report (Ref. 4) did not review of all 
    of the psyllium studies that were publicly available prior to 1988 and 
    identified in the petition (Ref. 35). The petition identified 16 
    clinical studies, published prior to 1989, of the effect of psyllium 
    seed husk on blood cholesterol levels (see Ref. 35, Table 3). The 
    agency had not reviewed these studies in the psyllium husk proposed 
    rule, but in response to the comment, has subsequently considered them. 
    Half of these studies did not meet the agency's stated criteria for 
    selection of human studies (62 FR 28234 at 28237) in that they were 
    conducted in special populations, were published as abstracts only, or 
    the psyllium dose was unreported. Studies that used special population 
    groups were excluded from review because, as explained in the psyllium 
    husk proposed rule (62 FR 28234 at 28237), the results from such groups 
    may not be relevant to the general healthy U.S. population. The
    
    [[Page 8107]]
    
    agency's rationale for excluding from review studies presented only in 
    abstracts was also presented in the proposal. Abstracts do not provide 
    sufficient detail regarding the methodology and results to allow a 
    detailed assessment of the merits of the study. Likewise, information 
    regarding actual amounts of psyllium administered is a key detail of 
    the study design, without which an adequate assessment of the study 
    cannot be made.
        In each of the pre-1989 clinical studies meeting the selection 
    criteria, there were aspects of the study design (e.g., lack of dietary 
    data, lack of a control group) that would have precluded the results of 
    these studies from having a major influence on the agency's 
    conclusions. Among the pre-1989 clinical studies was one double-blind 
    placebo-controlled psyllium husk study with dietary data (Ref. 36). 
    However, the report contained no evidence that the study subjects were 
    compliant with a low saturated fat and cholesterol diet. Thus, a review 
    by FDA of pre-1989 data would not have altered the conclusions reached 
    by the agency in the psyllium husk proposed rule nor contribute to 
    issuing the final rule.
        The agency disagrees with the comments that there is not 
    significant scientific agreement that soluble fiber from psyllium husk 
    may help reduce the risk of CHD through its action on blood total- and 
    LDL-cholesterol levels. Some of the comments incorrectly suggested that 
    the agency's decision on this nutrient/disease relationship was based 
    solely on the results of the seven studies in Table 1 of the psyllium 
    husk proposed rule (62 FR 28234 at 28244). As stated previously, the 
    agency reviewed 21 human studies on psyllium (Refs. 8 through 28) that 
    were submitted with the petition and met the agency's criteria for 
    consideration (Ref. 7). Of these, the agency gave particular weight to 
    seven studies. As stated in the psyllium husk proposed rule, the 
    results of the seven studies (Refs. 13 through 15, 18, 22, 23, and 28), 
    and now three additional studies (Refs. 12, 17, and 25) (see comment 3 
    in section II.B.1 of this document), strongly support the relationship 
    between soluble fiber from psyllium husk and risk of CHD in mild to 
    moderate hypercholesterolemic adults (62 FR 28234 at 28238). Moreover, 
    the results of the remaining clinical studies (Refs. 8 through 11, 16, 
    19 through 21, 24, and 26) that were given less weight in the psyllium 
    husk proposed rule were consistent in showing an effect of soluble 
    fiber from psyllium husk on serum lipid levels. These studies included 
    both men and women subjects and adults of all ages, including the 
    elderly. It is on the totality of this evidence and conclusions from 
    the 1989 Life Sciences Research Office (LSRO) report on health 
    consequences of dietary fiber (Ref. 5) that the agency is basing its 
    conclusion to authorize a health claim on psyllium seed husk.
    3. Psyllium Consumed as a Bulk Laxative
        In the psyllium husk proposed rule, the agency included in its 
    evaluation the results of studies of this nutrient/disease relationship 
    in which psyllium was administered as a product marketed as a bulk-
    forming fiber laxative.
    (Comment 5)
        Some comments were opposed to the consideration of studies in which 
    psyllium husk was supplied as a bulk-forming fiber laxative. One 
    comment stated that the use of studies in which psyllium seed husk was 
    consumed in different forms makes meaningful comparisons difficult. 
    Other comments had no objection to the agency's use of this evidence. 
    One comment stated that consuming psyllium husk as a bulk-forming fiber 
    laxative at mealtime is functionally equivalent to consuming a psyllium 
    husk-enriched food at mealtime. Another comment stated that clinical 
    studies evaluating psyllium seed husk administered as a bulk-forming 
    fiber laxative were conducted in a fashion similar to studies conducted 
    with food products, including consuming the substance at mealtime, 
    dietary counseling, and patient selection criteria. The comment stated 
    that both compliance with the regimen and efficacy were comparable for 
    food and laxative studies.
        In the psyllium husk proposed rule, the agency tentatively decided 
    that including, in its comprehensive review, the three studies in which 
    psyllium seed husk was administered in the form used as a laxative 
    (Refs. 13, 15, and 18) was appropriate. In these studies, the psyllium 
    seed husk was consumed in concentrations similar to those at which 
    psyllium husk was incorporated into conventional foods in the other 
    studies selected for comprehensive review (Refs. 14, 22, 23, and 28) 
    (62 FR 28234 at 28238). The agency further noted that the magnitude of 
    the effect of soluble fiber from psyllium husk on the change in serum 
    lipid levels reported in the studies in which this substance was 
    consumed in conventional foods (Refs. 14, 22, 23, and 28) was similar 
    to that observed in the studies (Refs. 13, 15, and 18) in which it was 
    consumed as a bulk laxative. Therefore, the agency stated that the 
    results of the studies suggest that the form in which psyllium husk is 
    consumed is not significant when evaluating the effect of psyllium husk 
    on serum lipid levels (62 FR 28234 at 28238). Comments that were 
    opposed to reliance on studies which used a psyllium husk bulk-forming 
    laxative provided no new data to support their position. Therefore, the 
    agency is not persuaded that it is inappropriate to rely on this 
    evidence and concludes that studies that used a psyllium husk bulk-
    forming laxative are appropriate in the evaluation of this nutrient/
    disease relationship.
    4. Studies in Subjects With Borderline to High Blood Cholesterol Levels
        The subject populations in the studies reviewed in the psyllium 
    proposed rule (see Table 1, 62 FR 28234 at 28244) had borderline to 
    high blood total-cholesterol levels (i.e., average baseline cholesterol 
    values in the studies were between 225 and 275 mg/dL). The agency 
    tentatively concluded in the psyllium proposed rule that the studies 
    with hypercholesterolemic subjects are relevant to the general U.S. 
    population (62 FR 28234 at 28238) and requested comments on this issue.
    (Comment 6)
        Some comments agreed with the agency's view that studies of 
    populations with elevated blood cholesterol are relevant to the general 
    population. These comments cited current statistics of the incidence of 
    elevated blood cholesterol in the U.S. population, and noted that the 
    CHD risk factor that is the target of the proposed health claim is 
    elevated blood cholesterol. Other comments disagreed with the view that 
    the results of studies in hypercholesterolemics can be generalized to 
    the general population. One comment stated that because 
    hypercholesterolemic individuals are generally more responsive to 
    dietary intervention that normocholesterolemic individuals, it is 
    questionable whether normocholesterolemic persons would respond to 
    psyllium at all.
        As the leading cause of death in this country, CHD is a disease for 
    which the general U.S. population is at risk. The risk of dying from 
    CHD is related to serum cholesterol levels in a continuous and positive 
    manner, increasing slowly for levels between 150 mg/dl and 200 mg/dl 
    and more rapidly when the cholesterol level exceeds 200 mg/dl (Ref. 
    37). The public health policy elucidated by the National Cholesterol 
    Education Program (NCEP), National Heart, Lung, and Blood Institute, is 
    to extend the benefits of cholesterol lowering to the population as a 
    whole by promoting adoption of eating patterns that can help lower the 
    blood cholesterol levels of most Americans
    
    [[Page 8108]]
    
    (Ref. 37). A dietary intervention that lowers blood cholesterol levels 
    only in persons with high levels would, like an intervention that 
    lowers cholesterol levels across the entire population range, cause a 
    shift in the population distribution of blood cholesterol levels 
    resulting in a decrease in the mean value for the blood cholesterol 
    level in the general population (Ref. 37). The anticipated effect of 
    such a shift would be to reduce the morbidity from CHD and to produce a 
    continued or accelerated decline in the CHD mortality rate in the 
    United States. The agency is persuaded by the evidence it has reviewed 
    in this rulemaking that the consumption of psyllium seed husk, as part 
    of a low saturated fat and cholesterol diet, can be a prudent public 
    health measure to assist in the national policy of promoting eating 
    patterns that will help in achieving or maintaining desirable blood 
    cholesterol levels in the general population. Therefore, it concludes 
    that the health claim is relevant to the general population and should 
    not be limited to a subpopulation of hypercholesterolemic individuals. 
    In addition, consistent with the agency's conclusions in rulemaking on 
    the dietary saturated fat and cholesterol/CHD claim (58 FR 2739 at 
    2745, January 6, 1993), the wording of the health claim as ``may' or 
    might' reduce the risk of heart disease'' adequately represents the 
    fact that not all persons will realize the same magnitude of benefit 
    from adopting the dietary change.
    
    C. Issues Relative to Amending Sec. 101.81 to Include Soluble Fiber 
    From Psyllium Seed Husk
    
        In the psyllium husk proposed rule, the agency tentatively 
    concluded that the soluble fiber in psyllium husk, like -
    glucan soluble fiber from whole oats, when consumed as part of a diet 
    low in saturated fat and cholesterol, may help reduce the risk of heart 
    disease. Therefore, the agency proposed to amend the authorized claim 
    for -glucan soluble fiber from whole oats and risk of CHD 
    (Sec. 101.81) to include soluble fiber from psyllium husk and to 
    broaden the subject of the claim to ``soluble fiber from certain 
    foods'' and risk of CHD.
    (Comment 7)
        One comment stated that Sec. 101.81 should not be expanded to 
    include soluble fiber from psyllium husk because the eligible sources 
    of -glucan soluble fiber are whole grain foods that provide 
    nutrients in addition to soluble fiber, whereas psyllium seed husk, 
    which offers only soluble fiber, is neither a food nor a whole grain. 
    The comment also stated that psyllium seed husk should not be added to 
    Sec. 101.81 because the husk soluble fiber is separated from the whole 
    seed, whereas -glucan soluble fiber extracted from the whole 
    oat grain is not eligible for a claim. Two comments suggested that if 
    the claim must be structured as a soluble fiber claim, then only those 
    soluble fiber sources that elicit clinically significant reductions in 
    serum cholesterol via the same mechanism should be eligible to be 
    included in the claim.
        FDA disagrees with the comment that substances qualifying for a 
    health claim under Sec. 101.81 must be whole grains similar to the 
    whole oats that are listed under Sec. 101.81(c)(2)(ii)(A). The subject 
    of the claim is soluble fiber and the food source of -glucan 
    soluble fiber is whole oats. There is no scientific basis to require 
    that only soluble fiber from whole grain foods can qualify for a claim. 
    The soluble fiber in psyllium seed is concentrated in the outer husk. 
    This is the opposite from whole oats where the soluble fiber is 
    concentrated in the inner portion of the oat groat. Moreover, purified 
    -glucan soluble fiber was not included as a substance eligible 
    to bear the claim because, as discussed in the whole oat final rule, 
    the hypocholesterolemic properties of -glucan fiber extracts 
    are affected by processing. Therefore, before an extract of -
    glucan fiber could qualify for the claim, it would have to be 
    characterized so as to identify the processed form of the soluble fiber 
    that maintains its hypocholesterolemic properties. The data on psyllium 
    husk soluble fiber are associated with reduced risk of CHD via its 
    documented hypocholesterolemic properties. As discussed previously (see 
    comment 2 in section II.A.2 of this document), psyllium seed husk is a 
    ``substance'' eligible for consideration of a health claim within the 
    meaning of that term in Sec. 101.14(a)(2). Therefore, the agency finds 
    it appropriate to consider soluble fiber from psyllium seed husk as a 
    source of soluble fiber that is eligible to be included in Sec. 101.81.
        The agency also disagrees with the comment that a soluble fiber 
    source should not be included in Sec. 101.81 unless it elicits 
    reductions in serum cholesterol via the same mechanism as the 
    -glucan soluble fiber in whole oats. There is no scientific 
    basis to require soluble fibers to have the same mechanism of action 
    for lowering serum cholesterol in order to be eligible for a health 
    claim under Sec. 101.81, nor did the comments provide such a basis. In 
    the whole oat final rule, the agency stated that if a manufacturer can 
    document that a soluble fiber product has an effect on blood lipid 
    levels, and thereby can be useful in reducing the risk of CHD, the 
    manufacturer may petition to amend Sec. 101.81 to include that type of 
    soluble fiber-containing product as an eligible food source (62 FR 3584 
    at 3588). In this rulemaking, the agency has concluded that consumption 
    of soluble fiber from psyllium seed husk has an effect of lowering 
    blood total- and LDL-cholesterol levels, and therefore an amendment to 
    Sec. 101.81 to include psyllium seed husk as a soluble fiber source is 
    eligible for a health claim under Sec. 101.81.
    
    D. Specifications for Psyllium Seed Husk
    
        Based upon information provided by the petitioner, the agency 
    proposed a minimum psyllium husk purity specification as a qualifying 
    criterion for eligible sources of soluble fiber from psyllium. Proposed 
    Sec. 101.81(c)(2)(ii)(B)(1) stated that psyllium husk shall have a 
    purity of:
    
    no less than 95 percent, such that it contains 3 percent or less 
    protein, 4.5 percent or less of light extraneous matter, and 0.5 
    percent or less of heavy extraneous matter, but in no case may the 
    combined extraneous matter exceed 4.9 percent * * *.
    
    (62 FR 28234 at 28243).
    1. Issues Relative to Psyllium Seed Husk Specifications
    (Comment 8)
        One comment noted that there are no assurances that food 
    manufacturers other than the petitioner will be able to meet the 
    petitioner's product specifications and therefore a compliance 
    monitoring program needs to be developed prior to authorization of the 
    health claim. A comment noted that due to natural variability in 
    psyllium seed husk and analytical variation, a ``94 percent purity'' 
    specification would better represent the practical limit of 
    commercially-available ``95 percent purity'' psyllium. Accordingly, 
    this comment urged FDA to adopt a minimum psyllium husk purity of 94 
    percent with 5.0 percent or less of light extraneous matter and 1.0 
    percent or less of heavy extraneous matter. One comment expressed 
    concern that the purification of psyllium husk may render psyllium 
    inactive as a hypocholesterolemic agent. This comment also urged FDA to 
    determine whether the purification process described by the petitioner 
    should serve as the approved purification technique for psyllium.
        The agency disagrees with the comment that a specific compliance 
    monitoring system is needed for psyllium seed husk. The monitoring and
    
    [[Page 8109]]
    
    verification of compliance with current good manufacturing practice in 
    the manufacture of human food is a routine FDA activity. The comment 
    urging the agency to change the psyllium husk purity specification to 
    ``no less than 94 percent'' provided no data to substantiate that 
    commercial supplies of psyllium seed husk do not routinely meet the 95 
    percent purity specification and the agency sees no compelling reason 
    to revise the proposed purity specifications. Accordingly, the agency 
    is adopting the specifications proposed in Sec. 101.81(c)(2)(ii)(B)(1).
        The agency notes that evidence provided in the petition and in 
    comments indicates that the psyllium seed husk in the food and bulk 
    laxative products used in the clinical studies, which were discussed in 
    the psyllium husk proposed rule, had a purity of at least 95 percent. 
    The blood cholesterol lowering effect of psyllium seed husk is 
    attributed to the soluble fiber content of the husk and not to the seed 
    components. As such, the concern that the process of separating the 
    psyllium husk from residual seed components would alter the 
    effectiveness of psyllium husk in lowering blood cholesterol level is 
    unfounded. The agency further notes that it has proposed to adopt a 
    psyllium husk purity specification only, and not a purification 
    process.
    
    E. Nature of the Food Eligible to Bear the Claim
    
        In the proposal, the agency determined a qualifying level of 
    psyllium husk for foods eligible to bear a soluble fiber and CHD claim 
    based on a daily intake of approximately 7 g of soluble fiber from 
    psyllium seed husk (62 FR 28234 at 28240). The agency stated that the 
    level of daily intake of soluble fiber from psyllium seed husk (7 g/d 
    was not based on the results of data from a dose-response study, but 
    was the amount shown in clinical studies to be consistently associated 
    with significant reductions in serum lipids in conjunction with a diet 
    low in saturated fat and cholesterol. Therefore, the agency proposed 
    that the qualifying level of soluble fiber for foods to bear a soluble 
    fiber and CHD claim be 1.7 g of soluble fiber from psyllium seed husk 
    per RACC (7 g divided by 4 eating occasions per day) (62 FR 28234 at 
    28240). The agency asked for comments on whether this approach for 
    establishing a qualifying soluble fiber level for psyllium husk-
    containing products is appropriate or for data to support another 
    qualifying level for psyllium husk.
    1. Qualifying Criteria for Psyllium Seed Husks
    (Comment 9)
        Some comments stated that it is premature to authorize this health 
    claim because of the limited data regarding an appropriate dose-
    response curve. One comment stated that the qualifying level for 
    psyllium should be based on an intake level that will elicit a 
    clinically significant 5 percent reduction in blood cholesterol. The 
    comment stated that results from dose-response and meta-analysis 
    studies would assuage concerns that the proposed qualifying level of 
    soluble fiber from psyllium seed husk may not be an effective 
    cholesterol-lowering dose. Other comments agreed with the proposed 
    qualifying level for psyllium-containing foods. One comment stated that 
    the revised report of the dose-response study by Davidson et al. (Ref. 
    14), that was submitted with the comment, supports the effectiveness of 
    10.2 g psyllium husk daily intake in significantly lowering cholesterol 
    levels. In an analysis of data from subjects who completed the protocol 
    (197 of 286 subjects), LDL-cholesterol levels of the group with 10.2 g 
    psyllium husk daily intake was reported to be 5 percent lower than the 
    control group after 24 weeks. The comment also stated that the data 
    from the meta-analysis by Olson et al. (Ref. 34), which was submitted 
    with the comment, lends additional support to the conclusion that 10.2 
    g/d of psyllium is an appropriate level on which to base the qualifying 
    criteria for this claim. One comment stated that the maximum level of 
    daily psyllium husk consumption should be determined as part of the 
    generally recognized as safe (GRAS) process.
        FDA notes that dose-response data are not a requirement to 
    establish the qualifying criteria for a substance that is the subject 
    of a health claim. Under Sec. 101.70, which describes the requirements 
    for health claim petitions, the petition must address whether there is 
    an optimum level of the particular substance to be consumed beyond 
    which no benefit would be expected (Sec. 101.70(f)B.1.). This 
    information may or may not be based on dose-response data. Even though 
    the optimal or lowest effective cholesterol lowering doses can not be 
    determined from the available data, the qualifying level (10.2 g/d of 
    psyllium husk) has been demonstrated to be effective. The results of 
    studies that evaluated the effect of psyllium husk intakes above 10.2 
    g/d showed no additional benefit on serum lipid levels (Ref. 7). 
    Therefore, the agency disagrees with the comments stating that dose-
    response data are needed before the agency can authorize a health 
    claim. The totality of scientific data, which establish a significant 
    reduction in blood cholesterol based on an intake of 10.2 g/d of 
    psyllium seed husk, provides an adequate basis for establishing a 
    qualifying soluble fiber level for psyllium seed husk-containing 
    products.
        Similarly, there is no basis to require that the qualifying 
    criteria for a substance associated with risk of CHD be based on the 
    amount of that substance to elicit a 5 percent reduction in blood 
    total- and LDL-cholesterol levels. The data on psyllium seed husk 
    suggests that the magnitude of the effect on blood lipids for intakes 
    of about 10 g/d of psyllium seed husk ranges from 4 to 6 percent for 
    blood total-cholesterol and about 4 to 8 percent for LDL-cholesterol 
    levels in conjunction with diets low in saturated fat and cholesterol 
    (Ref. 7). Although modest in size, these are clinically significant 
    reductions in blood lipids that translate to a reduced risk of CHD for 
    individuals with hypercholesterolemia and serve as a useful adjunct to 
    a diet already low in saturated fat and cholesterol.
        In the absence of data to the contrary, the agency concludes that 
    based on the evidence submitted in comments and on the totality of 
    scientific data considered in its review of the petition, a daily 
    intake of 7 g of soluble fiber from psyllium seed husk (10.2 g of 
    psyllium seed husk) as part of a diet low in saturated fat and 
    cholesterol may reduce the risk of CHD by lowering blood total- and 
    LDL-cholesterol levels in individuals with mild to moderate 
    hypercholesterolemia.
        FDA finds that the comment that a maximum level of daily 
    consumption of psyllium husk should be determined as part of the 
    psyllium husk GRAS status is not relevant to this rulemaking.
    2. Issues Relative to Four Eating Occasions Per Day
    (Comment 10)
        The proposed qualifying level of soluble fiber from psyllium husk 
    was based on the assumption that individuals will consume four servings 
    of psyllium husk-containing foods a day. Some comments questioned 
    whether it is realistic to assume that consumers will consume four 
    servings per day of psyllium husk-containing foods. One comment stated 
    that the majority of Americans never consume any psyllium husk-
    containing foods and that there is no evidence that a health claim 
    would convince them to consume up to four servings of these foods 
    daily. Other comments stated that the proposed rule would provide 
    consumers
    
    [[Page 8110]]
    
    with an increased selection of foods containing soluble fiber in 
    sufficient quantities to have a potentially beneficial influence on CHD 
    risk and thus have a positive public health impact.
        FDA acknowledges that foods containing psyllium seed husk are not 
    widely available; e.g., the petitioner currently produces only one 
    product, a breakfast cereal, containing psyllium. However, the agency 
    disagrees with the comments that it is unrealistic to consider that 
    consumers could consume psyllium-containing foods four times a day. Two 
    studies (Refs. 8 and 14) that were reviewed by the agency tested 
    psyllium seed husk incorporated into a variety of foods that were 
    consumed during the day. These products included cereal, fruit drinks, 
    peanut butter, cookies, muffins, bread, pasta, and snack bars. In 
    addition to these products, the petitioner identified other food 
    products in which psyllium could be used, such as toaster pastries, 
    rolls, biscuits, tortillas, waffles, pancakes, pizza crust, stuffing, 
    breakfast bars, and a variety of ready-to-eat cereals (Ref. 35, pp. 90 
    and 91). Authorization of a claim on soluble fiber from psyllium seed 
    husk will be an incentive for manufacturers to expand product lines to 
    provide consumers with additional soluble fiber-containing products 
    that can be part of a heart healthy diet. Based on these facts, the 
    agency finds that a factual predicate exists to support the contention 
    that psyllium husk-containing foods could be consumed at four eating 
    occasions a day and, therefore, finds that the comments that questioned 
    whether such consumption was realistic are without support.
        The agency notes that the approach used to determine the qualifying 
    level of soluble fiber from psyllium husk (i.e., dividing the amount 
    shown to provide a significant reduction in blood lipid levels by 4 
    eating occasions per day) is consistent with that used to determine the 
    qualifying level of -glucan soluble fiber from whole oats in 
    the soluble fiber from whole oats final rule. In that document, the 
    agency pointed out that the approach used to derive the qualifying 
    level of soluble fiber from whole oats is somewhat different from that 
    used in authorizing other health claims. It stated:
        Specifically, the guiding principle for other health claims is 
    to use the established definition for ``good source'' or ``high'' 
    which characterizes the amount of a nutrient, based on a percentage 
    of the Daily Value (DV) for the nutrient, in a serving of food. In 
    this way, products that qualify to bear the claim contain a 
    meaningful level of the substance per serving compared to the 
    recommended intake of the substance from all food sources. In the 
    case of this final rule, there is no DV for -glucan soluble 
    fiber or soluble fiber.
    (62 FR 3584 at 3592).
    The agency had also indicated in the soluble fiber from whole oat final 
    rule that it intends to propose to establish a Daily Reference Value 
    (DRV) for soluble fiber (62 FR 3584 at 3588). The establishment of a 
    DRV for soluble fiber would not only permit claims for ``good source'' 
    and ``high'' in soluble fiber, but would allow the agency to consider 
    amendments to Sec. 101.81 to establish a single qualifying level for 
    soluble fiber from all eligible soluble fiber sources that would be 
    effective in lowering cholesterol. Available scientific evidence 
    suggests that there are a variety of soluble fibers in foods that may 
    demonstrate the benefit. Thus, smaller dietary contributions from any 
    one source could be appropriate given the potential for multiple 
    sources of such fibers.
        A DRV for soluble fiber would establish a qualifying level for 
    soluble fiber blends in a food that would be effective in lowering 
    cholesterol in hypercholesterolemic individuals. However, in the 
    absence of a DRV for soluble fiber, the qualifying criteria for the 
    eligible sources of soluble fiber in this health claim must be based on 
    the scientific evidence specific for each soluble fiber source. The 
    agency intends to amend Sec. 101.81 to revise the qualifying levels of 
    soluble fibers when a DRV for soluble dietary fiber has been 
    established.
        The agency notes that existing Sec. 101.81(d)(6) provides for an 
    optional statement informing consumers of the level of daily intake of 
    -glucan from whole oats that may help reduce the risk of CHD 
    and the contribution that one serving of the product makes to this 
    specified intake level. However, when issuing the soluble fiber from 
    whole oats and reduced risk of CHD health claim, FDA inadvertently 
    overlooked the requirement in Sec. 101.14(d)(2)(vii) of the general 
    requirements for health claims. That section states that if the claim 
    is about the effects of consuming the substance at other than decreased 
    levels, and if no definition for ``high'' has been established (e.g., 
    where the claim pertains to a food either as a whole food or as an 
    ingredient in another food), the claim must specify the daily dietary 
    intake necessary to achieve the claimed effect, as established in the 
    regulation authorizing the claim.
        As stated, FDA has not established a DRV for soluble fiber. As a 
    result, the term ``high'' is not defined for soluble fiber. Therefore, 
    consistent with Sec. 101.14(d)(2)(vii), a claim for soluble fiber from 
    whole oats requires specification of the daily dietary intake from 
    whole oats (3 g or more per day of -glucan soluble fiber from 
    whole oats) necessary to achieve a reduction in the risk of CHD. This 
    requirement is independent of the optional statement provided in 
    Sec. 101.81(d)(6).
        When discussing the optional statement under Sec. 101.81(d)(6) in 
    the soluble fiber from whole oats final rule, FDA stated that when the 
    amount of soluble fiber to be consumed per day is stated, the amount 
    per serving is also needed so that consumers would not be misled to 
    believe that a serving of the food contributes the full daily amount 
    (62 FR 3584 at 3596). Therefore, to be consistent with the current 
    regulation in Sec. 101.14(d)(2)(vii) and with the need to specify the 
    amount of soluble fiber that a serving of food contributes when the 
    daily dietary intake is specified in the claim, the agency is 
    requiring, under Sec. 101.81(c)(2)(i)(G), that this information be 
    included in a health claim for both whole oats and psyllium husk 
    soluble fiber claims. However, because FDA did not note this 
    requirement in the soluble fiber from whole oats final rule, firms 
    currently marketing foods that bear the health claim for whole oats may 
    wait until the next printing of their food labels and labeling for such 
    foods to incorporate this added information.
        Therefore, the agency is adding Sec. 101.81(c)(2)(i)(G) in this 
    final rule to clarify current regulatory requirements. Existing 
    Sec. 101.81(d)(6), which provides for the same information for whole 
    oats as an optional statement, is being removed. Accordingly, 
    Sec. 101.81(c)(2)(i)(G) states that the claim shall specify that an 
    intake of 7 g or more per day of soluble fiber from psyllium seed husk, 
    or an intake of 3 g or more per day of -glucan soluble fiber 
    from whole oats may help reduce the risk of CHD. Such a claim must be 
    accompanied by information on the contribution that one serving of the 
    product makes to the specified daily dietary intake level. Any foods 
    containing psyllium seed husk, or whole oats, and bearing the health 
    claim are required to include this information as part of the claim.
    3. Blends of Eligible Soluble Fibers
        In the psyllium husk proposed rule, the agency noted that foods 
    might be produced with a blend of the eligible soluble fibers listed in 
    Sec. 101.81(c)(2)(ii) and stated that it would be willing to consider 
    whether such foods should be eligible to bear the health claim (62 FR 
    28234 at 28240). However, the agency stated that it does not have the 
    data from which to evaluate the relationship between consumption of 
    foods
    
    [[Page 8111]]
    
    containing both psyllium and whole oats and risk of heart disease, and 
    cannot assume that foods containing a blend of these grains would have 
    the same ability to affect blood total- and LDL-cholesterol levels when 
    compared to a product containing either whole oats or psyllium. In the 
    proposal, the agency encouraged manufacturers to petition to amend 
    Sec. 101.81 further if it can be demonstrated that a diet that is low 
    in saturated fat and cholesterol that includes a blend of the eligible 
    soluble fibers listed in Sec. 101.81(c)(2)(ii) has an effect on the 
    risk of heart disease.
    (Comment 11)
        One comment agreed with the agency's tentative conclusion not to 
    include blends of the eligible soluble fibers at this time. The comment 
    stated that data should be submitted to verify the effectiveness of any 
    soluble fiber blend.
        The agency agrees that data are needed to verify the effectiveness 
    of blends of soluble fiber. In the absence of a review of such data, 
    FDA is not including the option of a blend of the eligible soluble 
    fibers listed in Sec. 101.81(c)(2)(ii) in this final rule. While some 
    studies submitted to the agency did evaluate the usefulness of soluble 
    fiber mixtures in lowering blood cholesterol levels, they were outside 
    the scope of this rulemaking, which pertains to the effects of soluble 
    fiber from psyllium alone. As a result, time and resource constraints 
    did not allow for an indepth review of how blends of eligible soluble 
    fibers might work in synergy with one another. Such a task would better 
    be addressed as a part of rulemaking to establish a DRV for soluble 
    fiber and a review of qualifying levels.
    
    F. Soluble Fiber From Certain Foods and From Eligible Food Sources
    
        In the psyllium husk proposed rule, the agency proposed to modify 
    the section heading of Sec. 101.81 from ``Soluble fiber from whole oats 
    and risk of coronary heart disease'' to ``Soluble fiber from certain 
    foods and risk of coronary heart disease'' (62 FR 28234 at 28241). The 
    agency stated that:
        ``soluble fiber from certain foods'' reflects the fact that the 
    subject of the claim is no longer a specific source of soluble 
    fiber, i.e., beta-glucan from whole oats, but rather a broader class 
    of substances that includes those sources of soluble fiber for which 
    there is significant scientific agreement that they may help to 
    reduce the risk of heart disease.
    (62 FR 28234 at 28241).
    The agency also proposed to revise the statement ``soluble fiber from 
    whole oats'' in Sec. 101.81(a), (a)(3), (b), (b)(2), (c)(2)(i), 
    (c)(2)(i)(A), (d)(3), and (e) to state ``soluble fiber from certain 
    foods,'' and in Sec. 101.81(c)(2)(i)(E), (c)(2)(i)(F), and (d)(2) to 
    read ``soluble fiber from the eligible food sources from paragraph 
    (c)(2)(ii) of this section'' (62 FR 28234 at 28241).
    (Comment 12)
        The agency received one comment that raised issues relative to the 
    agency's decision to modify the soluble fiber from whole oats and CHD 
    rule to a claim on soluble fiber from certain foods. This comment 
    argued that the final rule for Sec. 101.81 inappropriately refocused 
    this claim from ``whole oats'' to ``soluble fiber from whole oats'' and 
    heart disease. The comment asserted that -glucan was included 
    in the whole oats proposed rule only as a quantitative measure of whole 
    oats for compliance purposes. This comment further argued that because 
    the eligible source of -glucan soluble fiber is whole oat 
    products whereas the eligible source of psyllium soluble fiber is an 
    isolated fiber-rich fraction (e.g., husk) separated from the whole 
    psyllium seed, these substances should not be combined in one 
    regulation.
        The agency disagrees that the focus of Sec. 101.81 should be whole 
    oats. The rationale for positioning this claim as a soluble fiber claim 
    was explained in the soluble fiber from whole oats final rule (62 FR 
    3584 at 3585).
    
    G. Issues Relative to the Safety of Psyllium Seed Husk
    
        Prior to submitting the health claim petition, the petitioner had 
    petitioned FDA to affirm that the use of psyllium seed husk in grain-
    based foods is GRAS (55 FR 4481, February 8, 1990). In the psyllium 
    husk proposed rule, the agency noted that although FDA has reached no 
    decision on the GRAS affirmation for the use of this substance, the 
    petition appears to contain evidence that the use of psyllium seed husk 
    at levels necessary to justify a claim is safe and lawful, as required 
    by Sec. 101.14(b)(3)(ii) (62 FR 28234 at 28236). However, the agency 
    indicated that there are some public safety concerns with the 
    consumption of psyllium seed husk (e.g., colonic epithelial cell 
    proliferation, allergenicity, and gastrointestinal obstruction). The 
    agency asked for comments on whether these concerns would be a basis 
    for not authorizing the proposed health claim. The agency also 
    recognized that an increase in psyllium consumption is likely if the 
    proposed health claim is authorized (62 FR 28234 at 28236). Therefore, 
    the agency asked for comments on what type of actions may be necessary 
    to ensure that long-term consumption of psyllium seed husk will be at 
    safe levels, e.g., limiting psyllium husk content of foods or the kinds 
    of foods that can bear a claim.
    1. Restrictions on Psyllium Husk Content of Foods or on Types of Foods 
    That Can Bear a Claim.
    (Comment 13)
        FDA received several comments regarding the safety of psyllium 
    husk-containing foods. Some comments stated that psyllium husk has a 
    long history of safe human consumption as a laxative product at the 
    intake level upon which the qualifying food level of psyllium husk is 
    based. Furthermore, the comments noted that prior authoritative reviews 
    of the safety of psyllium husk in food, such as the 1993 LSRO 
    evaluation of the safety of psyllium seed husk as a food ingredient 
    (Ref. 39), concluded that there were no grounds to suggest that 
    consumption of as much as 25 g/d of psyllium husk would be a hazard to 
    the public. These comments argued that therefore it is unnecessary for 
    FDA to restrict the types of psyllium husk-containing food products, 
    the amount of psyllium husk that may be in a food product, or the 
    amount of psyllium husk that should be consumed per day as conditions 
    for use of the soluble fiber from psyllium husk health claim. Other 
    comments asserted that there is inadequate information about limits of 
    how much psyllium husk can be incorporated into foods, or about safe 
    levels of intake for long-term consumption. These comments argued that 
    there should be limits placed on permissible levels of psyllium husk in 
    foods and types of foods to which psyllium husk may be added. One 
    comment suggested that psyllium husk-containing foods be required to 
    bear a label statement warning consumers of the maximum amount of 
    psyllium husk that should be consumed per day.
        FDA agrees that there is a history of human oral consumption of 
    psyllium husk, both in food and over-the-counter (OTC) products, at the 
    daily intake level contemplated for this health claim. The daily intake 
    of psyllium husk that FDA has concluded is effective in reducing CHD 
    risk (10.2 g psyllium husk, which is the amount of psyllium husk that 
    is necessary to provide 7 g of soluble fiber) is well below the daily 
    intake level that the 1993 LSRO psyllium husk report (Ref. 39) 
    concluded was safe (i.e., 25 g psyllium husk). FDA does not expect 
    authorization of the health claim to result in potential psyllium husk 
    consumption exceeding this safe level.
        The 1993 LSRO report based its calculation of the potential daily 
    intake of psyllium husk, for a consumer preferentially selecting 
    products containing psyllium husk, on the
    
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    selection of four servings of psyllium husk-containing foods per day. 
    FDA considers four servings per day to be a reasonable estimate of 
    consumption for several reasons.
        First, consumers who are looking for foods that are identified as 
    useful in reducing risk of CHD need not seek only psyllium-husk 
    containing foods. They will also be able to select from foods that use 
    the health claims approved for foods low in saturated fat and 
    cholesterol (Sec. 101.75 (21 CFR 101.75)); for fruits, vegetables, and 
    grain products that contain fiber, particularly soluble fiber 
    (Sec. 101.77); and for foods containing soluble fiber from whole oats 
    (Sec. 101.81).
        Second, many types of frequently-consumed foods will not offer 
    psyllium husk-containing alternatives. For example, foods such as raw 
    meat, fish, and poultry; eggs; fats and oils; nuts and seeds; and raw 
    fruits and vegetables are not suitable candidates for the addition of 
    psyllium husk. In addition, technological or organoleptic effects of 
    the use of psyllium husk at levels needed to make a health claim will 
    limit its use in other categories of foods.
        Third, because the subject health claim is only allowed on foods 
    that are low in fat, saturated fat, and cholesterol, not all foods to 
    which psyllium husk could be feasibly be added would be eligible to 
    bear a health claim. Thus, there would be no incentive for a 
    manufacturer to add psyllium husk to such foods, other than at the 
    small amounts that may be used for technological purposes (e.g., 
    emulsifiers or binders).
        Lastly, most of the new psyllium husk-containing foods that are 
    expected to be developed are grain-based and as such are often used as 
    alternates for one another in usual dietary patterns (e.g., cereals, 
    breakfast bars, toaster pastries, rolls, biscuits, pancakes, or waffles 
    served at breakfast).
        For the mentioned reasons, FDA, in evaluating this health claim, 
    considers the selection of four servings of psyllium husk-containing 
    foods per day to be a reasonable expectation of consumption when 
    considering the possible use of psyllium husk in all food categories.
        Estimation of the potential daily intake of psyllium husk is also 
    dependent upon the amount of the ingredient in each food. In the 1993 
    LSRO report, maximum levels of use were reported as designated by the 
    Kellogg Co. at 7.5 percent by weight for bread-based products (e.g., 
    bread, rolls, muffins, doughnuts, biscuits, tortillas, waffles, 
    pancakes, pizza crust and stuffing), pasta, and toaster pastries. In 
    addition, the maximum levels of use were reported to be 10 percent by 
    weight for breakfast bars, and 15 percent by weight for ready-to-eat 
    cereals (Ref. 39). Assuming the highest maximum level of use, 15 
    percent in ready-to-eat cereals, the consumption of four 30 g servings 
    (i.e., the reference amount customarily consumed for high fiber cereals 
    (Sec. 101.12(b) Table 2)) would result in a daily intake of 18 g (30 g 
    multiplied by 15 percent = 4.5 g/serving, multiply by 4 servings = 18 
    g/d). Moreover, any technological uses of psyllium husk in foods are at 
    such low levels (e.g., 0.5 percent in frozen desserts) that they are 
    not likely to have a notable impact on total daily intake.
        A total daily intake of 18 g is within the range of intakes 
    considered safe in the 1993 LSRO report (i.e., up to 25 g/d) (Ref. 39). 
    However, FDA expects that actual consumption will be less than this 
    amount because the maximum use levels were designated prior to the 
    agency's establishment of the health claim qualifying level. FDA 
    expects that manufacturers who develop new psyllium husk-containing 
    foods would do so to make use of the health claim. As such, the health 
    claim qualifying level (i.e., 2.6 g per reference amount) would be a 
    major factor in determining the amount of psyllium husk to include in 
    new psyllium husk-containing foods.
        Based on these considerations, the agency disagrees with the 
    comments that argued that limits should be placed on permissible levels 
    of psyllium husk in foods or on the types of foods to which psyllium 
    husk may be added. Therefore, no changes are being made to 
    Sec. 101.81(c)(iii)(A)(2) that describes the nature of the food.
        As noted in the psyllium husk proposed rule (62 FR 28234 at 28235), 
    a preliminary review of the petitioner's GRAS affirmation petition 
    revealed that it contains significant evidence supporting the safety of 
    the consumption of up to 25 g/d of psyllium husk in a variety of food 
    categories (i.e., types of foods). This amount is well in excess of the 
    levels necessary to justify a health claim (i.e., 10.2 g/d) and the 
    amounts that would reasonably be expected to be consumed in a day. 
    Accordingly, based on the totality of the evidence, FDA is not at this 
    time taking issue with the petitioner's view that the use of psyllium 
    husk is safe and lawful. Therefore, the agency concludes that the 
    petitioner has provided evidence that satisfies the requirements in 
    Sec. 101.14(b)(3)(ii) that psyllium seed husk at the levels necessary 
    to justify a claim is safe and lawful.
    (Comment 14)
        Several comments discussed evidence from animal studies suggesting 
    that the relationship between effects of dietary fiber on rodent 
    colonic mucosal proliferation and the development of neoplasia is 
    unclear. These comments stated that colonic epithelial cell 
    proliferation is not a significant issue relative to the safety of 
    psyllium seed husk as there is no consensus as to whether epithelial 
    cell proliferation in rodent colonic mucosa is relevant to risk of 
    colon cancer. Some comments noted that colonic epithelial cell 
    proliferation is an issue of concern that needs additional research.
        The agency agrees that colonic epithelial proliferation is not 
    sufficiently validated as a reliable endpoint for prediction of colon 
    tumorigenesis. While the rate of epithelial cell proliferation in the 
    rodent gastrointestinal tract has been reported to be increased by some 
    soluble dietary fibers and decreased by some insoluble dietary fibers, 
    there is no evidence upon which to conclude that the influence of 
    dietary fiber on the rate of epithelial proliferation is either adverse 
    or beneficial. Whether psyllium husk influences colonic epithelial cell 
    proliferation in humans as it does in rodents is unknown. Although 
    enhanced cellular proliferation is associated with the neoplastic 
    process, proliferation rates have been reported to be variably 
    influenced by a number of dietary constituents and other exogenous and 
    endogenous factors, and a significant overlap in proliferation rates 
    between subjects at high and low risk of colon cancer has been observed 
    (Ref. 40). Therefore, the agency concludes that the issue of epithelial 
    cell proliferation is not a basis on which to deny this health claim.
    2. Allergic Potential of Psyllium Husk
        In the psyllium husk proposed rule, the agency acknowledged reports 
    of allergic reactions from consumption of psyllium husk-containing 
    food. The majority of these reports involved ingestion of a cereal made 
    with psyllium husk of less than 95 percent
    
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    purity. Because information provided by the petitioner suggested that 
    the purity of the psyllium husk is inversely related to its 
    allergenicity, FDA proposed a purity criterion for psyllium husk to be 
    eligible for the claim. Under comment 8 in section II.D.1 of this 
    document, the agency stated that psyllium husk purity specifications of 
    proposed Sec. 101.81(c)(2)(ii)(B)(1) are being adopted in the final 
    rule.
    (Comment 15)
        Two comments stated that the declaration of an ingredient in the 
    ingredient list of the food label is sufficient labeling to alert 
    consumers to the presence of allergenic components in foods and that 
    additional labeling is unnecessary. Other comments stated that in 
    consideration of the allergic potential of psyllium, the presence of 
    psyllium husk in a food should be declared on the principal display 
    panel in addition to the ingredient declaration.
        Some comments agreed with the proposed husk purity specifications 
    as an adequate means of reducing the potential for allergic responses. 
    One comment explained that the major source of allergenic proteins in 
    psyllium seed husk is from residual portions of the whole seed. The 
    comment stated that the removal of the inner seed portions leaves a 
    very low level of residual protein in 95 percent purity psyllium husk 
    and thus, the potential for serious allergic reactions would be rare. 
    However, the comment also suggested that a label statement with an 
    appropriate caution as to the risk for allergic reactions would provide 
    added assurances for consumers. Still other comments argued that the 
    proposed purity standards for psyllium seed husk will not eliminate the 
    risk for allergic reactions to psyllium husk-containing foods and as 
    such, a cautionary statement alerting consumers to the risk of allergic 
    reactions should be required labeling. None of the comments provided 
    data.
        The agency is not convinced by these comments that labeling, other 
    than declaration in the ingredient statement when psyllium husk is 
    added as a food ingredient, is necessary because of psyllium's allergic 
    potential. The agency recognizes the possibility of isolated cases of 
    allergic reactions to ingested allergenic substances in foods or food 
    components, including psyllium seed husk. However, the agency believes 
    that the declaration of the allergenic substance in the ingredient list 
    on the food label provides adequate information for consumers regarding 
    the presence of allergenic ingredients in food products. Psyllium seed 
    husk is required to be declared in the ingredient statement of a food 
    to which it is added. The agency has no basis for concluding that 
    additional labeling requirements for the use of this health claim would 
    have an impact on reducing the potential for allergic reactions from 
    consumption of psyllium husk-containing foods. The agency would not 
    object to any additional truthful, nonmisleading information regarding 
    allergenicity that a manufacturer may wish to include on the food 
    label.
    3. Gastrointestinal Obstruction
        In the psyllium proposed rule, the agency discussed the potential 
    for esophageal and gastrointestinal obstructions to occur following 
    consumption of psyllium seed husk when not consumed with sufficient 
    liquid (62 FR 28234 at 28236). The agency noted that the LSRO expert 
    panel (Ref. 39) reported that esophageal and gastrointestinal 
    obstruction due to psyllium seed husk was associated almost exclusively 
    with consumption without proper hydration of bulk-forming fiber 
    laxatives and not with consumption of psyllium-containing cereal 
    consumed with milk (62 FR 28234 at 28236). Comments were requested on 
    whether psyllium husk-containing foods should carry a statement 
    advising that the product be consumed with liquids, or whether the 
    potential for blockage is not an issue of concern for psyllium husk-
    containing food (62 FR 28234 at 28236).
    (Comment 16)
        Several comments discussed the potential for esophageal and 
    gastrointestinal obstructions from consumption of psyllium husk without 
    sufficient liquid. These comments recommended that the agency adopt 
    labeling requirements for psyllium husk-containing foods advising 
    consumers to drink adequate fluids when consuming such foods. Some of 
    these comments suggested that such statements be similar to those 
    required under Sec. 201.319 (21 CFR 201.319) (Warning Statements 
    Required for Over-the-Counter Drugs Containing Water-Soluble Gums as 
    Active Ingredients (58 FR 45194, August 26, 1993)) for OTC products to 
    ensure consumers are aware of the consequences of inadequate hydration. 
    In general, these comments justified their recommendations on the basis 
    that authorization of the proposed health claim would encourage 
    incorporation of psyllium seed husk into additional types of foods, and 
    that these new food products containing significant amounts of psyllium 
    seed husk will not necessarily be intended to be consumed with liquids. 
    One comment asserted that a label statement advising the consumption of 
    the psyllium husk-containing food with liquids is unnecessary because 
    psyllium husk-containing foods would be consumed at meals when it is 
    likely that sufficient liquid would also be consumed. The comment 
    argued that the soluble fiber in psyllium husk-containing foods is 
    already hydrated, which would reduce its ability to swell in the 
    gastrointestinal tract. This comment further noted that the 1993 LSRO 
    report on the safety of using psyllium seed husk as a food ingredient 
    (Ref. 39) found no safety issues in this regard. None of the comments 
    provided data.
        The agency agrees with comments suggesting that authorization of a 
    claim for soluble fiber from psyllium husk and risk of CHD may lead to 
    an increase in the number and type of foods containing psyllium husk. 
    Moreover, the agency agrees that there are no assurances that new 
    psyllium husk-containing foods are likely to be consumed at meals or 
    with liquids. Foods such as cookies, breakfast bars, and toaster 
    pastries may be consumed as snacks at times when a liquid is not 
    consumed. Psyllium husk could also be incorporated into dietary 
    supplement products that may be consumed apart from meals. The comment 
    that stated that the psyllium seed husk in foods is already hydrated, 
    which would affect its ability to swell in the gastrointestinal tract, 
    provided no data to document or with which to evaluate differences in 
    the swell volume and rate of swelling of different psyllium husk-
    containing foods.
        The LSRO expert panel that considered the safety of psyllium seed 
    husk used as a food ingredient (Ref. 39) concluded that the moderate 
    amounts of psyllium seed husk that are likely to be used in toaster 
    pastries, bread-based products, breakfast bars, pasta, and cereals 
    would not be expected to cause gastrointestinal obstruction. However, 
    this panel further concluded that the possibility of obstruction would 
    be reduced by suitable suggestions that these products be consumed with 
    fluids.
        The agency addressed the risk of esophageal obstruction by water 
    soluble gums (including psyllium husk) in an advance notice of proposed 
    rulemaking to establish a monograph for OTC laxative, antidiarrheal, 
    emetic, and antiemetic drug products (40 FR 12902, March 21, 1975). The 
    agency discussed in the final rule the evidence of at least 191 cases 
    of esophageal obstruction and 8 cases of asphyxia, resulting in 18 
    deaths, associated with orally-administered OTC laxative and weight 
    control products containing a variety of
    
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    water soluble gums (58 FR 45194 at 45195). The agency concluded that 
    there is a risk that these types of products will swell to form a 
    viscous adhesive mass (i.e., viscous gel) that can block the throat or 
    esophagus. Because of this risk, the agency requires warning and 
    direction statements for OTC drug products containing water soluble 
    gums, including psyllium husk, as active ingredients when these 
    products are marketed in a dry or partially hydrated form 
    (Sec. 201.319). Fully hydrated water soluble gums were acknowledged to 
    not pose any significant risk of causing esophageal obstruction (58 FR 
    45194 at 45196).
        In the final rule on ``Warning Statements Required for OTC Products 
    Containing Water-Soluble Gums as Active Ingredients,'' the agency 
    stated that it will continue to evaluate the use of water-soluble gums 
    in any product marketed for human consumption, food or drug, and 
    appropriate warnings will be proposed if a need to do so is found (58 
    FR 45194 at 45196).
        The agency anticipates that authorization of a health claim for 
    soluble fiber from psyllium husk may result in an increase of both the 
    type and number of foods containing psyllium husk, and that foods 
    eligible to bear the psyllium husk health claim will contain amounts of 
    psyllium husk comparable to that commonly found in OTC laxative drugs. 
    However, the agency recognizes that there are inherent differences 
    between foods in conventional food form, which contain other food 
    ingredients such as salt, sugar, and flour in addition to psyllium 
    husk, and OTC drug products that would influence the likelihood of 
    esophageal obstruction occurring from the ingestion of psyllium husk-
    containing foods. For example, drug products are formulated in tablets, 
    capsules, and powders that are usually intended to be ingested and 
    swallowed as a single bolus, whereas a serving of food is not swallowed 
    as a single bolus, but eaten in several bites, chewed, and swallowed 
    over a period of time. Psyllium husk-containing conventional foods also 
    differ from drug products in that the psyllium husk in a food in 
    conventional food form is dispersed within a larger volume of other 
    food components (e.g., sugars, salt, wheat flour, egg). Dispersion in 
    other ingredients prevents the soluble fiber of psyllium husk from 
    physically associating to form a gel network (i.e., a viscous adhesive 
    mass) (Refs. 41 and 42). Because a strong gel network is not formed due 
    to the presence of these other ingredients, the food product will swell 
    and thicken in a similar fashion to other high fiber foods (e.g., 
    ready-to-eat cereals), without forming a viscous mass capable of 
    causing obstruction (Ref. 42). The agency believes that, because the 
    composition and manner of consumption of psyllium husk-containing 
    conventional foods, unlike OTC products, inhibit the formation of a 
    viscous gel in the esophagus, the label requirements for OTC drug 
    products may not be applicable to certain foods containing psyllium 
    husk that bear a health claim.
        Section 201(n) of the act (21 U.S.C. 321(n)) states that, in 
    determining whether labeling is misleading, the agency shall take into 
    account not only representations made about the product, but also the 
    extent to which the labeling fails to reveal facts material in light of 
    such representations made or suggested in the labeling or material with 
    respect to consequences which may result from use of the article to 
    which the labeling relates under the conditions of use as are customary 
    or usual (see 21 CFR 1.21). Thus, the omission of certain material 
    facts from the label or labeling on a food causes the product to be 
    misbranded within the meaning of sections 403(a)(1) and 201(m) of the 
    act (21 U.S.C. 343(a)(1)).
        As discussed out in the final rule on warning statements for OTC 
    products (58 FR 45194), esophageal obstruction and asphyxiation are 
    potential health risks associated with the oral consumption of dry or 
    incompletely hydrated psyllium husk when these products are ingested 
    without adequate fluid or when they are used by individuals with 
    esophageal narrowing or dysfunction, or with difficulty swallowing. 
    There is the possibility that esophageal obstruction and choking from 
    ingestion of psyllium husk-containing food would be a consequence of 
    extending the food use of psyllium husk to certain types of food 
    products, such as those that are predominately composed of psyllium 
    husk. Therefore, FDA has determined that the potential for esophageal 
    blockage from not consuming adequate amounts of fluids when consuming 
    certain types of dry or incompletely hydrated psyllium husk-containing 
    food is a material fact.
        The agency concludes that it would be misleading under section 
    201(n) of the act for certain foods to contain dry or incompletely 
    hydrated psyllium husk without a label statement relative to potential 
    risks and concerns for adequate fluid intake. Therefore, in this final 
    rule FDA is amending its regulations to require a statement 
    [hereinafter ``label statement''] to inform consumers of the potential 
    consequence if the psyllium husk-containing food is not consumed 
    appropriately, to inform consumers of the action necessary to avoid the 
    consequence, and to advise persons with swallowing difficulties to 
    avoid consumption of the product.
        Because the concern for esophageal obstruction exists whether or 
    not the food bears a health claim, FDA is codifying the need for the 
    required label statement in Sec. 101.17 Food labeling warning and 
    notice statements (21 CFR 101.17) rather than in the health claim 
    regulation. The required label statement is also reflected in 
    Sec. 101.81(c)(1). Accordingly, FDA is adding paragraph (f)(1) to 
    Sec. 101.17 to specify that when dry or incompletely hydrated psyllium 
    husk is present in a food and the food bears a health claim, the label 
    must include a statement such as:
        The food should be eaten with at least a full glass of liquid. 
    Eating this product without enough liquid may cause choking. Do not 
    eat this product if you have difficulty swallowing.
        In the psyllium proposed rule, the agency had specifically 
    requested comments on whether psyllium husk-containing foods should 
    carry a statement advising that the product be consumed with liquids. 
    However, the agency had not suggested that it was considering requiring 
    labeling for all psyllium husk-containing foods regardless of whether 
    the food label bears a health claim statement. Therefore, FDA is not 
    attempting, in this final rule, to extend the required statement to 
    psyllium husk-containing foods not subject to this rulemaking, i.e., 
    foods not bearing a health claim. Instead, the agency plans to propose, 
    in a separate rulemaking, that the required label statement be extended 
    to other psyllium husk-containing foods that do not bear a health 
    claim.
        However, as discussed previously, the agency recognizes that there 
    are factors that suggest that the formation of a viscous adhesive mass, 
    which is associated with a risk of choking, does not result from 
    consumption of certain psyllium husk-containing foods that are in a 
    conventional food form. Therefore, the agency believes that certain dry 
    or incompletely hydrated conventional food products, i.e., those that 
    do not form a viscous adhesive mass under usual conditions of use, 
    would not require the label statement. The agency believes that an 
    exemption from the label statement should be available to firms when a 
    viscous adhesive mass is not formed when the product is exposed to 
    fluids so that the product poses no greater risk to the consumer than a 
    comparable product without psyllium husk. The agency does not currently
    
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    have data or information on which it could base such an exemption for 
    specific conventional food products. Moreover, because FDA, under 
    Sec. 101.70(j)(4)(i), is obligated to publish this final rule within 
    the time limitation established for issuing final rules for health 
    claim proceedings, the agency is unable, in this final rule, to specify 
    the conditions under which exemptions to the label statement for 
    certain conventional food products are warranted. Consequently, the 
    agency will provide firms that seek such an exemption with guidance as 
    to what would be necessary to demonstrate that such an exemption to the 
    label statement is warranted. The agency will further evaluate the need 
    for the label statement on specific types of psyllium husk-containing 
    foods that bear a health claim in the separate rulemaking that will 
    address the extension of the label statement to psyllium husk-
    containing foods that do not bear a health claim. If the agency 
    challenges a firm's determination that its conventional food product is 
    entitled to the exemption in Sec. 101.17(f)(1), and as a result is not 
    misbranded within the meaning of section 201(n) of the act without such 
    label statement, the agency will evaluate the basis for the firm's 
    exemption on a case-by-case basis.
        Section 403(f) of the act requires that mandatory label information 
    be prominently placed on the label with such conspicuousness (compared 
    with other words, statements, designs, or devices in the labeling) as 
    to render it likely to be read and understood by the ordinary 
    individual under customary conditions of use. FDA has generally 
    considered the label information panel to be the appropriate location 
    for notice and warning statements. As discussed in the agency's 
    rulemaking requiring warning statements on iron-containing dietary 
    supplements (62 FR 2218, January 15, 1997), consumer focus group 
    studies establish that a warning statement need not be placed on the 
    principal display panel (PDP) to be effective in informing consumers of 
    the hazard. Participants in the focus groups reasoned that the front of 
    the product package was used for marketing purposes and stated that 
    they were accustomed to looking at the ``back of products'' for 
    nutrition and factual information, including warning statements (Ref. 
    43). Consequently, in the case of iron-containing dietary supplements, 
    the agency required that the warning statement appear on the 
    information panel.
        The agency believes that for the required label statements on 
    psyllium husk-containing products, the requirement for prominence and 
    conspicuousness would similarly be met if the statements appeared on 
    the information panel. However, the agency would not object to firms 
    placing the required statement on the PDP, because the PDP would 
    provide even greater prominence. Accordingly, FDA is requiring in 
    Sec. 101.17(f)(2) that the required statement for psyllium husk-
    containing foods appear either on the product information panel or on 
    the PDP.
        The requirement in the act for prominent display means that the 
    required label statement must appear in a manner that makes it readily 
    observable and likely to be read. The agency notes that 21 CFR 101.2(c) 
    requires that mandatory information appearing on the PDP and 
    information panel, including information required by Sec. 101.17, 
    appear prominently and conspicuously in a type size no less than one-
    sixteenth inch.
        In addition, current agency regulations that require a ``warning'' 
    statement on the product label or in labeling (e.g., the statement 
    required by Sec. 101.17(e) on iron-containing dietary supplements in 
    solid oral dosage form) or a label ``notice'' statement (e.g., the 
    statement required by Sec. 101.17(d)(3) on protein products that are 
    not covered by the requirements of Sec. 101.17(d)(1) and (d)(2)) 
    require that the identifying term ``WARNING'' or ``NOTICE'' be 
    capitalized and immediately precede the language of the applicable 
    labeling statement. Based on FDA's experience in rulemaking pertaining 
    to warning statements on protein products (47 FR 25379, June 11, 1982), 
    as the severity of the consequences lessens, the severity of the 
    warning may also lessen. Therefore, the agency considers the term 
    ``NOTICE'' to be appropriate to alert consumers to the label statement. 
    Accordingly, the agency is requiring in Sec. 101.17(f)(2) that the 
    capitalized word ``NOTICE'' immediately precede the required elements 
    of the label statement.
    4. Laxative effects
    (Comment 17)
        One comment noted that psyllium husk is primarily consumed for its 
    laxative effect. This comment asserted that the label and labeling of 
    psyllium husk-containing foods should inform consumers about the 
    adverse effects of consuming excess amounts of psyllium by including a 
    disclosure statement such as ``Consumption of psyllium in excess of --
    -- mg may cause diarrhea.'' Other comments noted that intake of 
    psyllium-containing foods is self-limiting due to satiety and laxative 
    effects.
        FDA disagrees that the possible effects on bowel function of 
    consuming 10 g/d of psyllium seed husk in foods would be considered as 
    causing diarrhea or an adverse health consequence. Diarrhea is 
    characterized by loose, watery bowel movements. The water-holding 
    capacity and bulking effect of undigested soluble fiber from psyllium 
    husk softens colonic contents and stimulates peristalsis, both of which 
    facilitate movement of the colonic contents. Ingestion of psyllium husk 
    does not lead to diarrhea. The expected effect of the use of bulk-
    forming fiber laxatives is an increase in stool volume and frequency of 
    bowel movements. There is no reason to consider that a daily intake of 
    10 g of psyllium seed husk as a component of food would have any effect 
    on the bowel other than to promote normal functioning by softening 
    fecal contents and increasing fecal volume. Because the daily intake of 
    psyllium seed husk that is approved for this health claim is the same 
    customary daily intake when used as a laxative, amounts in excess of 
    that required for laxation are not needed to obtain potential benefits, 
    in reduced risk of CHD, from consumption of psyllium seed husk. 
    Moreover, consumption in excess of 10.2 g/d of psyllium seed husk would 
    not be expected to result in diarrhea because intake of psyllium husk 
    increases stool volume and frequency of bowel movements. Softening of 
    fecal contents is not diarrhea and does not represent an adverse health 
    effect as suggested by the comment. Therefore, the agency finds that 
    there is no basis on which to require, as suggested by the comment, a 
    warning statement to alert consumers about possible adverse effects 
    from consuming psyllium husk-containing foods.
    
    H. General Health Claim Issues
    
    1. Health claims for substances with OTC drug uses.
    (Comment 18)
         One comment stated that approving a claim on a product that 
    incorporates an OTC drug into a food would set a precedent for allowing 
    claims on ``functional foods,'' foods consumed primarily for their 
    purported ability to prevent or treat disease. The comment stated that 
    this was not the intent of Congress when it passed the 1990 amendments.
        FDA notes that bran, as well as psyllium husk, are listed as 
    effective bulk-forming laxative active ingredients in the tentative 
    final monograph on laxative drug products for OTC human use (50 FR 
    2124, January 15, 1985) and that oat bran is also an eligible source of 
    soluble fiber from whole oats for this
    
    [[Page 8116]]
    
    health claim. The fact that a substance also has uses as an OTC drug 
    does not bear on its recognized status as a food. FDA notes that 
    psyllium seed husk is a recognized source of dietary fiber and an 
    established food ingredient. Therefore, the comment is not relevant to 
    this rulemaking.
    2. Food-Specific Health Claims
    (Comment 19)
        Some comments stated that the proposed claim for a specific soluble 
    fiber should not be authorized because claims for specific foods create 
    the false impression that consumption of those foods is a more 
    important factor than is the overall diet in reduction of risk of CHD. 
    Other comments asserted that allowing health claims for individual 
    substances portrays specific foods as panaceas or functional foods and 
    undermines the purpose of the 1990 amendments. One comment expressed 
    concern that claims about individual sources of dietary fiber are 
    inconsistent with the important dietary guidance of choosing diets high 
    in fruits, vegetables, whole grain foods, and other good sources of 
    fiber. One comment stated that the proposed claim does not inform the 
    consumer that frequent, long-term consumption of soluble fiber from 
    psyllium husk is necessary to lower cholesterol levels.
        FDA addressed the issue of the appropriate subject of health claims 
    in rulemaking leading to, and including, the January 6, 1993, final 
    rule on general requirements for health claims (see 56 FR 60537 at 
    60542, November 27, 1991; 58 FR 2478 at 2479, January 6, 1993). While 
    some comments to proposed rulemaking maintained that health claims 
    should only be permitted for nutrients listed in nutrition labeling, 
    others argued that Congress intended claims to be authorized for foods 
    as well as nutrients. Comments quoted private and public health 
    organizations' testimony before Congress that health claims should 
    reflect dietary recommendations about foods and ``should assist the 
    public to integrate specific food products into a well balanced diet'' 
    (58 FR 2478 at 2479). After extensive discussion, final rules 
    implementing the 1990 amendments defined health claims as claims 
    characterizing the relationship of any substance to a disease or 
    health-related condition, and defined ``substance'' as a specific food 
    or component of food (Sec. 101.14(a)(1) and (a)(2)). This permitted 
    health claims to be established for both nutrients and foods.
        In the soluble fiber from whole oats final rule, the agency 
    addressed comments that expressed concern that a claim on whole oat 
    foods would portray the specific food as a ``magic bullet'' in reducing 
    heart disease risk. This concern was ameliorated when the scientific 
    evidence supported changing the subject of the claim to soluble fiber 
    from whole oats. In addition, the importance of a total diet low in 
    saturated fat and cholesterol to the nutrient/disease relationship was 
    emphasized (62 FR 3584 at 3585 and 3590). FDA noted that diets low in 
    saturated fat and cholesterol are considered by expert groups to be the 
    most effective dietary means of reducing heart disease risk. The agency 
    stated that while soluble fiber from whole oats contributes to this 
    effect, its role is generally recognized as being of smaller magnitude 
    (62 FR 3584 at 3590 and 3594).
        Likewise, the agency concludes that the concerns described 
    previously that were raised in comments to the psyllium husk proposed 
    rule are adequately addressed by the fact that a health claim on 
    psyllium-containing foods will be required to state the subject of the 
    claim as ``soluble fiber from psyllium husk'' and to describe the 
    nutrient/disease relationship in the context of a diet low in saturated 
    fat and cholesterol. The comment provided no evidence to suggest that 
    health claims about specific foods or food ingredients will not 
    encourage consumers to follow dietary recommendations to eat a varied 
    diet containing other foods that are also good sources of fiber.
         FDA notes that the subject health claim, as is the case for all 
    authorized health claims, requires that the claim be stated in the 
    context of a daily diet. This is accomplished through specific 
    requirements describing the nature of the claim, i.e., the relationship 
    of the substance to the disease or health-related condition in 
    paragraph (c)(2)(i) of each health claim regulation. These requirements 
    are intended to show the nature of the relationship between the subject 
    of the claim and the disease or health condition and to prevent any 
    misunderstanding that health benefits will accrue from single or 
    infrequent consumption of the subject nutrient or adherence to the 
    suggested dietary regimen. Examples of such wording include 
    ``throughout life'' in the calcium/osteoporosis claim (21 CFR 101.72), 
    ``daily'' in the folate/neural tube defect claim (21 CFR 101.79), 
    ``diets low in fat * * *'' in health claims pertaining to cancer (21 
    CFR 101.73, 101.76, and 101.78) and ``diets low in saturated fat and 
    cholesterol * * *'' in health claims pertaining to heart disease 
    (Secs. 101.75, 101.77, and 101.81). Therefore, the agency is making no 
    changes in response to this comment.
        The preamble of the soluble fiber from whole oats health claim 
    final rule considered the impact of the health claim on consumer 
    perception of food label references to oats (62 FR 3584 at 3596). A 
    comment had suggested that as consumers become aware of the 
    relationship between soluble fiber from whole oats and reduced risk of 
    CHD, statements such as ``made with oat bran'' would be an implied 
    nutrient content or health claim. In response to this comment, FDA 
    stated that it did not have information from which to conclude that 
    terms such as ``oat bran,'' ``rolled oats,'' or ``whole oat flour'' are 
    always in a context that constitutes an implied nutrient content or 
    health claim, and as such FDA would continue its policy to evaluate the 
    context of label statements on a case-by-case basis (62 FR 3584 at 
    3597). The agency further noted that if experience with label 
    statements about oat ingredients or other information persuades FDA 
    that additional regulatory controls are needed, the agency can take 
    action to establish appropriate regulations. The agency does not have 
    reason at this time to change this policy.
    
    III. Environmental Impact
    
        The agency has previously considered the environmental effects of 
    this rule as announced in the psyllium husk proposed rule (62 FR 
    28234). The proposed rule incorrectly cited a claim of categorical 
    exclusion under previous 21 CFR 25.24(a)(11). The agency has 
    determined, based on information contained in an environmental 
    assessment prepared under previous 21 CFR 25.31a(b)(5), that this 
    action has no significant impact on the environment and that an 
    environmental impact statement is not required. No new information or 
    comments have been received that would affect this determination. The 
    agency's finding of no significant impact and the evidence supporting 
    that finding, contained in an environmental assessment, may be seen in 
    the Dockets Management Branch (address above) between 9 a.m. and 4 
    p.m., Monday through Friday.
    
    IV. Analysis of Economic Impacts
    
    A. Benefit-Cost Analysis
    
        FDA has examined the impacts of the final rule under Executive 
    Order 12866. Executive Order 12866 directs agencies to assess all costs 
    and benefits of available regulatory alternatives and, when regulation 
    is necessary, to select the regulatory approach that maximizes net 
    benefits (including potential
    
    [[Page 8117]]
    
    economic, environmental, public health and safety effects; distributive 
    impacts; and equity). According to Executive Order 12866, a rule is 
    significant if it meets any one of a number of specified conditions, 
    including having an annual effect on the economy of $100 million, 
    adversely affecting in a material way a sector of the economy, 
    competition, or jobs, or if it raises novel legal or policy issues. FDA 
    finds that this rule is not a significant rule as defined by Executive 
    Order 12866.
        In addition, FDA has determined that this rule does not constitute 
    a significant rule under the Unfunded Mandates Reform Act of 1995 
    requiring cost-benefit and other analyses. A significant rule is 
    defined in section 1531(a) as ``a Federal mandate that may result in 
    the expenditure by State, local, and tribal governments in the 
    aggregate, or by the private sector, of $100,000,000 (adjusted annually 
    for inflation) in any 1 year * * *.''
        Finally, in accordance with the Small Business Regulatory 
    Enforcement Fairness Act, the administrator of the Office of 
    Information and Regulatory Affairs of the Office of Management and 
    Budget has determined that this final rule is not a major rule for the 
    purpose of Congressional review.
        The authorization of health claims about the relationship between 
    soluble fiber from psyllium seed husk and CHD results in either costs 
    or benefits only to the extent that food manufacturers elect to take 
    advantage of the opportunity to use the claim. The authorization of the 
    health claim will not require that any labels be redesigned, or that 
    any product be reformulated. However, the labels of foods containing 
    whole oats and bearing the health claim will require revision to 
    specify the daily dietary intake of -glucan soluble fiber from 
    whole oats necessary to achieve the claim effect. Because FDA is 
    allowing firms to wait to incorporate this change with other regularly 
    scheduled changes, this provision will not result in additional costs.
        This final health claim will allow manufacturers to highlight the 
    benefits of soluble fiber from psyllium seed husk in addition to other 
    eligible food sources of soluble fiber for which FDA has already 
    approved a health claim. The benefit of establishing this health claim 
    is to provide for new information in the market regarding the 
    relationship between soluble fiber from psyllium seed husk and risk of 
    heart disease and to provide consumers with the assurance that this 
    information is truthful, not misleading, and scientifically valid.
    
    B. Small Entity Analysis
    
        FDA has examined the impacts of the final rule under the Regulatory 
    Flexibility Act (5 U.S.C. 601-612). If a rule has a significant 
    economic impact on a substantial number of small entities, the 
    Regulatory Flexibility Act requires agencies to analyze regulatory 
    options that would minimize the economic impact of that rule on small 
    entities.
        Small entities will incur costs only if they opt to take advantage 
    of the marketing opportunity presented by this regulation. FDA cannot 
    predict the number of small entities that will choose to use the claim. 
    However, no firm, including small entities, will choose to bear the 
    cost of redesigning labels unless they believe that the claim will 
    result in increased sales of their product. Therefore, this rule will 
    not result in either a decrease in revenues or a significant increase 
    in costs to any small entity. Accordingly, under the Regulatory 
    Flexibility Act, 5 U.S.C. 605(b), the agency certifies that this final 
    rule will not have a significant economic impact on a substantial 
    number of small entities.
    
    V. Paperwork Reduction Act
    
        In the psyllium proposal, FDA stated its tentative conclusion that 
    the proposed rule contained no information collection provisions 
    necessitating clearance by the Office of Management and Budget (OMB) 
    and asked for comments on whether the proposed rule imposed any 
    paperwork burden. No comments addressing the question of paperwork 
    burden were received. FDA has evaluated the final rule and concludes 
    that it contains no information collection provisions. Although the 
    final rule would amend Sec. 101.17 to require a label statement on 
    foods containing psyllium husk and bearing a health claim, FDA is 
    supplying the information that must be disclosed in the label 
    statement. Therefore, the label statement is a ``public disclosure of 
    information originally supplied by the Federal government to the 
    recipient for purpose of disclosure to the public'' (5 CFR 1320(c)(2)); 
    as such, it is not a ``collection of information'' subject to OMB 
    review under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et 
    seq.).
    
    VI. References
    
        The following references have been placed on display in the Dockets 
    Management Branch (address above) and may be seen by interested persons 
    between 9 a.m. and 4 p.m., Monday through Friday.
        1. Kellogg Co., Kellogg's Bran Buds Cereal with natural wheat 
    bran and psyllium (product packaging) Kellogg Co., Battle Creek, MI, 
    1997.
        2. The U.S. Pharmacopeia (USP 23), The National Formulary (NF 
    18), United States Pharmacopeial Convention, Inc., Rockville, MD, p. 
    1341-1342, 1995.
        3. DHHS, Public Health Service (PHS), ``The Surgeon General's 
    Report on Nutrition and Health,'' U.S. Government Printing Office, 
    Washington, DC, pp. 83-137, 1988.
        4. Food and Nutrition Board, National Academy of Sciences, 
    ``Diet and Health: Implications for Reducing Chronic Disease Risk,'' 
    National Academy Press, Washington, DC, pp. 291-309 and 529-547, 
    1989.
        5. LSRO, FASEB, ``Physiological Effects and Health Consequences 
    of Dietary Fiber,'' Bethesda, MD, 1987.
        6. LSRO, FASEB, ``Evaluation of Publicly Available Scientific 
    Evidence Regarding Certain Nutrient-Disease Relationships: 6. 
    Dietary Fiber and Cardiovascular Disease,'' Bethesda, MD, 1991.
        7. Saltsman, J., Memo to file with Table 1: ``Summary of 
    Clinical Trials: Psyllium and CHD,'' and Table 2: ``Psyllium and 
    CHD,'' Docket No. 96P-0338, Dockets Management Branch, January 28, 
    1997.
        8. Abraham, Z. D. and T. Mehta, ``Three-Week Psyllium-Husk 
    Supplementation: Effect on Plasma Cholesterol Concentrations, Fecal 
    Steroid Excretion, and Carbohydrate Absorption in Men,'' American 
    Journal of Clinical Nutrition, 47:67-74, 1988.
        9. Anderson, J. W., N. Zettwoch, T. Feldman, J. Tietyen-Clark, 
    P. Oeltgen, and C. W. Bishop, ``Cholesterol-Lowering Effects of 
    Psyllium Hydrophilic Mucilloid for Hypercholesterolemic Men,'' 
    Archives of Internal Medicine, 148:292-296, 1988.
        10. Anderson, J. W, T. L. Floore, P. B. Geil, D. S. O'Neal, and 
    T.K. Balm, ``Hypocholesterolemic Effects of Different Bulk-Forming 
    Hydrophilic Fibers as Adjuncts to Dietary Therapy in Mild to 
    Moderate Hypercholesterolemia,'' Archives of Internal Medicine, 
    151:1597-1602, 1991.
        11. Anderson, J. W., S. Riddell-Mason, N. J. Gustafson, S. F. 
    Smith, and M. Mackey, ``Cholesterol Lowering Effects of Psyllium-
    Enriched Cereal as an Adjunct to a Prudent Diet in the Treatment of 
    Mild to Moderate Hypercholesterolemia,'' American Journal of 
    Clinical Nutrition, 56:93-98, 1992.
        12. Anderson, J. W., M. H. Davidson, L. Blonde, W. V. Brown, W. 
    J. Howard, H. Ginsberg, L. D. Allgood, and K. W. Weingand, ``Long-
    Term Cholesterol-Lowering Effects of Psyllium as an Adjunct to Diet 
    Therapy in the Treatment of Hypercholesterolemia,'' Submitted to 
    Family Medicine.
        13. Bell, L. P., K. Hectorne, H. Reynolds, T. K. Balm, and D. B. 
    Hunninghake, ``Cholesterol-lowering Effects of Psyllium Hydrophilic 
    Mucilloid--adjunct Therapy to a Prudent Diet for Patients With Mild 
    to Moderate Hypocholesterolemia,'' Journal of the American Medical 
    Association (JAMA), 261:3419-23, 1989.
        14. Davidson, M. H., K. C. Maki, J. C. Kong, L. D. Dugan, S. A. 
    Torri, H. H. Hall, K. B.
    
    [[Page 8118]]
    
    Drennan, S. Anderson, V. Fulgoni, L. Saldanha, and B. Olson, ``Long-
    Term Effects of Consuming Psyllium-Enriched Foods on Serum Lipids,'' 
    accepted for publication in the American Journal of Clinical 
    Nutrition, 1997.
        15. Everson, G. T., B. P. Daggy, C. McKinley, and J. A. Story, 
    ``Effects of Psyllium Hydrophilic Mucilloid on LDL-Synthesis and 
    Bile Acid Synthesis in Hypercholesterolemic Men,'' Journal of Lipid 
    Research, 33:1183-1192, 1992.
        16. Gelissen, I. C., B. Brodie, and M. A. Eastwood, ``Effect of 
    Plantago Ovata (Psyllium) Husk and Seeds on Sterol Metabolism: 
    Studies in Normal and Ileostomy Subjects,'' American Journal of 
    Clinical Nutrition, 59:395-400, 1994.
        17. Keane, W. F., V. T. Miller, L. P. Bell, C. E. Halstenson, L. 
    D. Allgood, H. Tully, and J. C. LaRosa, ``Effect of Psyllium in 
    Conjunction With a Low-Fat Diet on Plasma Lipids in Elderly Patients 
    With Mild-to-Moderate Hypercholesterolemia,'' Unpublished, 1996.
        18. Levin, E. G., V. T. Miller, R. A. Muesing, D. B. Stoy, T. K. 
    Balm, and J. C. LaRosa, ``Comparison of Psyllium Hydrophilic 
    Mucilloid and Cellulose as Adjuncts to a Prudent Diet in the 
    Treatment of Mild to Moderate Hypercholesterolemia,'' Archives of 
    Internal Medicine, 150:1822-1827, 1990.
        19. Neal, G. W., and T. K. Balm, ``Synergistic Effects of 
    Psyllium in the Dietary Treatment of Hypercholesterolemia,'' 
    Southern Medical Journal, 83:1131-1137, 1990.
        20. Schectman, G., J. Hiatt, and A. Hartz, ``Evaluation of the 
    Effectiveness of Lipid-lowering Therapy (Bile Acid Sequestrants, 
    Niacin, Psyllium, and Lovastatin) for Treating Hypercholesterolemia 
    in Veterans,'' American Journal of Cardiology, 71:759-765, 1993.
        21. Sprecher, D. L., B.V. Harris, A. C. Goldberg, E. C. 
    Anderson, L. M. Bayuk, B. S. Russell, D. S. Crone, C. Quinn, J. 
    Bateman, B. R. Kuzmak, and L. D. Allgood, ``Efficacy of Psyllium in 
    Reducing Serum Cholesterol Levels in Hypercholesterolemic Patients 
    on High- or Low-Fat Diets,'' Annals of Internal Medicine, 119:545-
    554, 1993.
        22. Stoy, D. B., J. C. LaRosa, B. K. Brewer, M. Mackey, and R. 
    A. Muesing, ``Cholesterol-lowering Effects of Ready-to-Eat Cereal 
    Containing Psyllium,'' Journal of the American Dietetic Association, 
    93:910-912, 1993.
        23. Stoy, D. B., J. C. LaRosa, B. K. Brewer, L. G. Saldhanda, 
    and R. A. Muesing, ``Lipid Lowering Effects of Ready-to-Eat Cereal 
    Containing Psyllium: a Randomized Crossover Trial,'' Unpublished, 
    1993.
        24. Summerbell, C. D., P. Manley, D. Barnes, and A. Leeds, ``The 
    effects of Psyllium on Blood Lipids in Hypercholesterolaemic 
    Subjects,'' Journal of Human Nutrition and Dietetics, 7:147-151, 
    1994.
        25. Weingand, K. W., N-A. Le, B. R. Kuzmak, W. V. Brown, B. P. 
    Daggy, T. A. Miettinen, B. V. Howard, and W. J. Howard, ``Effects of 
    Psyllium on Cholesterol and Low-Density Lipoprotein Metabolism in 
    Subjects With Hypercholesterolemia,'' Endocrinology and Metabolism, 
    4:141-150, 1997.
        26. Gupta, R. R., C. G. Agrawal, G. P. Singh, and A. Ghatak, 
    ``Lipid-lowering Efficacy of Psyllium Hydrophilic Mucilloid in Non-
    insulin Dependent Diabetes Mellitus With Hyperlipidaemia,'' Indian 
    Journal of Medical Research, 100:237-241, 1994.
        27. Stewart, R. B., W. E. Hale, M. T. Moore, F. E. May, and R. 
    G. Marks, ``Effect of Psyllium Hydrophilic Mucilloid on Serum 
    Cholesterol in the Elderly,'' Digestive Diseases and Sciences, 36: 
    329-334, 1991.
        28. Jenkins, D., T. M. S. Wolever, E. Vidgon, C. W. C. Kendall, 
    T. P. P. Ransom, et al., ``Effect of Psyllium in 
    Hypercholesterolemia at Two Monounsaturated Fatty Acid Intakes,'' 
    American Journal of Clinical Nutrition, 65:1524-1533, 1997.
        29. Arjmandi, B. H., E. Sohn, S. Juma, S. R. Murphy, and B. P. 
    Daggy, ``Native and Partially Hydrolyzed Psyllium Have Comparable 
    Effects on Cholesterol Metabolism in Rats,'' Journal of Nutrition, 
    127:463-469, 1997.
        30. Daggy, B. P., N. C. O'Connell, G. R. Jerdack, B. A. Stinson, 
    and K. D. R. Setchell, ``Additive Hypocholesterolemic Effect of 
    Psyllium and Cholestyramine in the Hamster: Influence of Fecal 
    Sterol and Bile Acid Profiles,'' Journal of Lipid Research, 38:491-
    502, 1997.
        31. Fernandez, M. L., M. Vergara-Jiminez, K. Conde, T. Behr, and 
    G. Abdel-Fattah, ``Regulation of Apolipoprotein B-Containing 
    Lipoproteins by Dietary Soluble Fiber in Guinea Pigs,'' American 
    Journal of Clinical Nutrition, 65:814-822, 1997.
        32. Ganji, V., and C. V. Kies, ``Psyllium Husk Fiber 
    Supplementation to the Diets Rich in Soybean or Coconut Oil: 
    Hypocholesterolemic Effect in Healthy Humans,'' International 
    Journal of Food Science and Nutrition, 47:103-110, 1996.
        33. Jensen, C. D., W. Haskell, and J. Whittman, ``Long-Term 
    Effects of Water-Soluble Dietary Fiber in the Management of 
    Hypercholesterolemia in Healthy Men and Women,'' American Journal of 
    Cardiology, 79:34-37, 1997.
        34. Olson, B. H., S. M. Anderson, M. P. Becker, J. W. Anderson, 
    D. B. Hunninghake, D. J. A. Jenkins, J. C. LaRosa, J. M. Rippe, D. 
    C. K. Roberts, D. B. Stoy, C. D. Summerbell, A. S. Truswell. T. M. 
    S. Wolever, D. H. Morris, and V. L. Fulgoni III, ``Psyllium-Enriched 
    Cereals Lower Blood Total Cholesterol and LDL Cholesterol, but not 
    HDL Cholesterol, in Hypercholesterolemic Adults: Results of a Meta-
    Analysis,'' Journal of Nutrition, 127:1973-1980, 1997.
        35. Kellogg Co., ``Petition for Health Claim--Soluble Fiber from 
    Psyllium and Coronary Heart Disease,'' Item CP1, Docket 96P-0338, 
    Dockets Management Branch, June 12, 1996.
        36. Anderson, J. W., N. Zettwoch, T. Feldman, J. Tietyen-Clark, 
    P. Oeltgen, and C. W. Bishop, ``Cholesterol-lowering Effects of 
    Psyllium Hydrophilic Mucilloid for Hypercholesterolemic Men,'' 
    Archives of Internal Medicine, 148:292-296, 1988.
        37. DHHS, National Heart, Lung, and Blood Institute, National 
    Cholesterol Education Program, ``Report of the Expert Panel on 
    Population Strategies for Blood Cholesterol Reduction (Population 
    Panel Report),'' Chapter II. Background and Introduction, NIH 
    Publication No. 93-3046, Bethesda, MD, 1993.
        38. DHHS and USDA, ``Nutrition and Your Health: Dietary 
    Guidelines for Americans,'' 4th Ed., Home and Garden Bulletin No. 
    232, U.S. Government Printing Office, 1995.
        39. LSRO, ``The Evaluation of the Safety of Using Psyllium Seed 
    Husk as a Food Ingredient,'' Bethesda, MD, December 1993.
        40. Einspar, J. G., D. S. Alberts, S. M. Gapstur, R. M. Bostick, 
    S. S. Emmerson, and E. W. Gerner, ``Surrogate End-Point Biomarkers 
    as Measures of Colon Cancer Risk and Their Use in Cancer 
    Chemoprevention Trials,'' Cancer Epidemiology, Biomarkers and 
    Prevention, 6:37-48, 1997.
        41. Whistler & Daniel, in Food Chemistry, 2nd Ed., Fennema, O. 
    R., ed. Marcel Dekker, Inc., New York, pp. 108-112, 1985.
        42. Letter from V. L. Fulgoni, Kellogg's to C. J. Lewis, FDA, 
    December, 18, 1997.
        43. Memorandum from A. S. Levy, FDA, to K. Falci, FDA, June 26, 
    1997.
    
    List of Subjects in 21 CFR Part 101
    
        Food labeling, Incorporation by reference, Nutrition, Reporting and 
    recordkeeping requirements.
        Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
    authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
    101 is amended as follows:
    
    PART 101--FOOD LABELING
    
        1. The authority citation for 21 CFR part 101 continues to read as 
    follows:
    
        Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342, 
    343, 348, 371.
    
        2. Section 101.17 is amended by adding paragraph (f) to read as 
    follows:
    
    Sec. 101.17  Food labeling warning and notice statements.
    
    * * * * *
        (f) Foods containing psyllium husk. (1) Foods containing dry or 
    incompletely hydrated psyllium husk, also known as psyllium seed husk, 
    and bearing a health claim on the association between soluble fiber 
    from psyllium husk and reduced risk of coronary heart disease, shall 
    bear a label statement informing consumers that the appropriate use of 
    such foods requires consumption with adequate amounts of fluids, 
    alerting them of potential consequences of failing to follow usage 
    recommendations, and informing persons with swallowing difficulties to 
    avoid consumption of the product (e.g., ``NOTICE: This food should be 
    eaten with at least a full glass of liquid. Eating this product without 
    enough liquid may cause choking. Do not eat this product if you have 
    difficulty in swallowing.''). However, a product in conventional food 
    form may be exempt from this requirement if a viscous adhesive mass
    
    [[Page 8119]]
    
    is not formed when the food is exposed to fluids.
        (2) The statement shall appear prominently and conspicuously on the 
    information panel or principal display panel of the package label and 
    any other labeling to render it likely to be read and understood by the 
    ordinary individual under customary conditions of purchase and use. The 
    statement shall be preceded by the word ``NOTICE'' in capital letters.
        3. Section 101.81 is amended by revising the section heading, the 
    heading for paragraphs (a) and (b), and paragraphs (a)(3), (b)(2), 
    (c)(1), (c)(2)(i) introductory text, (c)(2)(i)(A), (c)(2)(i)(E), 
    (c)(2)(i)(F), (c)(2)(iii)(A), (d)(2), (d)(3), and (e); by adding 
    paragraphs (c)(2)(i)(G) and (c)(2)(ii)(B); and by removing paragraph 
    (d)(6) and redsignating paragraph (d)(7) as (d)(6) and paragraph (d)(8) 
    as (d)(7) to read as follows:
    
    
    Sec. 101.81  Health claims: Soluble fiber from certain foods and risk 
    of coronary heart disease (CHD).
    
        (a) Relationship between diets that are low in saturated fat and 
    cholesterol and that include soluble fiber from certain foods and the 
    risk of CHD. * * * 
    * * * * *
        (3) Scientific evidence demonstrates that diets low in saturated 
    fat and cholesterol may reduce the risk of CHD. Other evidence 
    demonstrates that the addition of soluble fiber from certain foods to a 
    diet that is low in saturated fat and cholesterol may also help to 
    reduce the risk of CHD.
        (b) Significance of the relationship between diets that are low in 
    saturated fat and cholesterol and that include soluble fiber from 
    certain foods and the risk of CHD. * * * 
    * * * * *
        (2) Intakes of saturated fat exceed recommended levels in the diets 
    of many people in the United States. One of the major public health 
    recommendations relative to CHD risk is to consume less than 10 percent 
    of calories from saturated fat and an average of 30 percent or less of 
    total calories from all fat. Recommended daily cholesterol intakes are 
    300 milligrams (mg) or less per day. Scientific evidence demonstrates 
    that diets low in saturated fat and cholesterol are associated with 
    lower blood total- and LDL-cholesterol levels. Soluble fiber from 
    certain foods, when included in a low saturated fat and cholesterol 
    diet, also helps to lower blood total- and LDL-cholesterol levels.
        (c) Requirements. (1) All requirements set forth in Sec. 101.14 
    shall be met. The label and labeling of foods containing psyllium husk 
    shall be consistent with the provisions of Sec. 101.17(f).
        (2) Specific requirements. (i) Nature of the claim. A health claim 
    associating diets that are low in saturated fat and cholesterol and 
    that include soluble fiber from certain foods with reduced risk of 
    heart disease may be made on the label or labeling of a food described 
    in paragraph (c)(2)(iii) of this section, provided that:
        (A) The claim states that diets that are low in saturated fat and 
    cholesterol and that include soluble fiber from certain foods ``may'' 
    or ``might'' reduce the risk of heart disease.
    * * * * *
        (E) The claim does not attribute any degree of risk reduction for 
    CHD to diets that are low in saturated fat and cholesterol and that 
    include soluble fiber from the eligible food sources from paragraph 
    (c)(2)(ii) of this section; and
        (F) The claim does not imply that consumption of diets that are low 
    in saturated fat and cholesterol and that include soluble fiber from 
    the eligible food sources from paragraph (c)(2)(ii) of this section is 
    the only recognized means of achieving a reduced risk of CHD.
        (G) The claim specifies the daily dietary intake of the soluble 
    fiber source that is necessary to reduce the risk of coronary heart 
    disease and the contribution one serving of the product makes to the 
    specified daily dietary intake level. Daily dietary intake levels of 
    soluble fiber sources listed in paragraph (c)(2)(ii) of this section 
    that have been associated with reduced risk coronary heart disease are 
    :
        (1) 3 g or more per day of B-glucan soluble fiber from whole oats.
        (2) 7 g or more per day of soluble fiber from psyllium seed husk.
        (ii) * * *
        (B)(1) Psyllium husk from the dried seed coat (epidermis) of the 
    seed of Plantago (P.) ovata, known as blond psyllium or Indian 
    psyllium, P. indica, or P. psyllium. To qualify for this claim, 
    psyllium seed husk, also known as psyllium husk, shall have a purity of 
    no less than 95 percent, such that it contains 3 percent or less 
    protein, 4.5 percent or less of light extraneous matter, and 0.5 
    percent or less of heavy extraneous matter, but in no case may the 
    combined extraneous matter exceed 4.9 percent, as determined by U.S. 
    Pharmacopeia (USP) methods described in USP's ``The National 
    Formulary,'' USP 23, NF 18, p. 1341, (1995), which is incorporated by 
    reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies 
    may be obtained from the U.S. Pharmacopeial Convention, Inc., 12601 
    Twinbrook Pkwy., Rockville, MD 20852, or may be examined at the Center 
    for Food Safety and Applied Nutrition's Library, 200 C St. SW., rm. 
    3321, Washington, DC, or at the Office of the Federal Register, 800 
    North Capitol St. NW., suite 700, Washington, DC;
        (2) FDA will determine the amount of soluble fiber that is provided 
    by psyllium husk by using a modification of the Association of Official 
    Analytical Chemists' (AOAC's) method for soluble dietary fiber (991.43) 
    described by Lee et al., ``Determination of Soluble and Insoluble 
    Dietary Fiber in Psyllium-containing Cereal Products,'' Journal of the 
    AOAC International, 78 (No. 3):724-729, 1995, which is incorporated by 
    reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies 
    may be obtained from the Association of Official Analytical Chemists 
    International, 481 North Frederick Ave., suite 500, Gaithersburg, MD 
    20877-2504, or may be examined at the Center for Food Safety and 
    Applied Nutrition's Library, 200 C St. SW., rm. 3321, Washington, DC, 
    or at the Office of the Federal Register, 800 North Capitol St. NW., 
    suite 700, Washington, DC;
        (iii) * * *
        (A) The food product shall include:
        (1) One or more of the whole oat foods from paragraph (c)(2)(ii)(A) 
    of this section, and the whole oat foods shall contain at least 0.75 
    gram (g) of soluble fiber per reference amount customarily consumed of 
    the food product; or
        (2) Psyllium husk that complies with paragraph (c)(2)(ii)(B) of 
    this section, and the psyllium food shall contain at least 1.7 g of 
    soluble fiber per reference amount customarily consumed of the food 
    product;
    * * * * *
        (d) * * *
        (2) The claim may state that the relationship between intake of 
    diets that are low in saturated fat and cholesterol and that include 
    soluble fiber from the eligible food sources from paragraph (c)(2)(ii) 
    of this section and reduced risk of heart disease is through the 
    intermediate link of ``blood cholesterol'' or ``blood total- and LDL-
    cholesterol;''
        (3) The claim may include information from paragraphs (a) and (b) 
    of this section, which summarize the relationship between diets that 
    are low in saturated fat and cholesterol and that include soluble fiber 
    from certain foods and coronary heart disease and the significance of 
    the relationship;
    * * * * *
        (e) Model health claim. The following model health claims may be 
    used in food labeling to describe the
    
    [[Page 8120]]
    
    relationship between diets that are low in saturated fat and 
    cholesterol and that include soluble fiber from certain foods and 
    reduced risk of heart disease:
        (1) Soluble fiber from foods such as [name of soluble fiber source 
    from paragraph (c)(2)(ii) of this section and, if desired, the name of 
    food product], as part of a diet low in saturated fat and cholesterol, 
    may reduce the risk of heart disease. A serving of [ name of food] 
    supplies ________ grams of the [grams of soluble fiber specified in 
    paragraph (c)(2)(i)(G) of this section] soluble fiber from [name of the 
    soluble fiber source from paragraph (c)(2)(ii) of this section] 
    necessary per day to have this effect.
        (2) Diets low in saturated fat and cholesterol that include 
    [________ grams of soluble fiber specified in paragraph (c)(2)(i)(G) of 
    this section] of soluble fiber per day from [name of soluble fiber 
    source from paragraph (c)(2)(ii) of this section and, if desired, the 
    name of the food product] may reduce the risk of heart disease. One 
    serving of [name of food] provides ________ grams of this soluble 
    fiber.
    
        Dated: February 10, 1998
    
    William B. Schultz,
    Deputy Commissioner for Policy.
    
    Note: The following table will not appear in the Code of Federal 
    Regulations.
    
                              Table 1.--Summary of Clinical Trials with Hypercholesterolemics: Psyllium and Coronary Heart Disease                          
    --------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                           Supplements         Diet Intake of                                               
        Study          Duration Treatment        Number of Subjects    (Psyllium, Placebo)  groups: Sat fat % E;    Magnitude of PSY    Magnitude of Placebo
                                                                        Soluble Fiber g/d         CHOL mg/d             Effect\1\              Effect       
    --------------------------------------------------------------------------------------------------------------------------------------------------------
    Anderson et    Base: 8 wk Step 1; Tx: 26   PSY: 131               10.2 g/d bulk         Sat fat: PSY- 8.3%;   CHOL: -5 mg/dL        CHOL: +5 (2.6%)     
     al.            wk Step 1+supplement       C: 28                   laxative, cellulose   C- 7.7%               (2.1%)\1\            LDL-C: +6 (3.9%)    
    (Ref. 13)                                                         PSY: 7 g  CHOL: PSY- 164 mg; C- LDL-C: -5 mg/dL       HDL-C: no sig dif   
                                                                       SF                     146 mg               (2.9%)\1\             (grps)             
    Bell et al.    Base: 12-wk Step 1; Tx: 8-  PSY: 40 (20 men)       10.2 g/d bulk         Sat fat: PSY- 8-10%;  CHOL: -9 mg/dL        CHOL: 0             
    (Ref. 14)       wk Step 1+supplement       Pla: 35 (18 men)        laxative, cellulose   C- 7.7-8.6%           (4.2%)               LDL-C: -0.2%        
                                                                      PSY: 7 g  CHOL: PSY- 168 mg; C- LDL-C: -12 mg/dL      HDL-C: no sig dif   
                                                                       SF                     206 mg               (7.7%)                (grps)             
    Davidson et    Base: 8-wk Step 1; Tx: 24-  PSY 1 56 (31 men)      3.4 g, 6.8 g, 10.2 g/ SAT fat: PSY- 7-      CHOL: -   CHOL: +1.7%; LDL-C: 
     al.            wk Step 1 + PSY or         PSY 2 40 (24 men)       d; incorporated       8.6%; C- 7-8.6%       3% (PSY 3)            +3%                
    (Ref. 15)       control food (3 servings/  PSY 3 43 (28 men)       into foods: C        CHOL: PSY 1- 151 mg;  LDL-C: -  HDL-C: No sig dif   
                    d)                         C 59                    foods: no PSY         PSY 2- 181; PSY 3-    5% (PSY 3)            (grps)             
                                                                      PSY 1:                 169                                                            
                                                                       2.3 g    C- 145 mg                                                       
                                                                       SF,                                                                                  
                                                                      PSY 2:                                                                                
                                                                       4.6 g;                                                                   
                                                                      PSY 3: 7                                                                  
                                                                       g                                                                                    
    Everson et     Regular diet; 5-d Base; 2   20 men                 15.3 g/d bulk         SAT fat: PSY- 12%; C- CHOL: -14 mg/dL (-    CHOL: -1.9%; LDL-C: -
     al.            40-d periods; 11-d                                 laxative, cellulose    13.2 %               5%)                   2.7%               
    (Ref. 16)       washout; crossover                                PSY: 10   CHOL: PSY- 296 mg; C- LDL-C: -15 mg/dL      HDL-C: No sig dif   
                                                                       g SF                   274 mg               (8%)                  (grps)             
    Keane et al.   Base: 12 wk Step 1; Tx: 26  PSY: 40 (18m, 24f)     10.2 g/d bulk         SAT fat: PSY- 5%; C-  CHOL: -8.7 mg/dL      CHOL: +2 (1%)       
    (Ref. 18)       wk Step 1+supplement       C: 39 (7m, 32f)         laxative, cellulose   5.3%                  (3%)                 LDL-C: 0            
                                                                      PSY: 7 g  CHOL: PSY- 145.2 mg;  LDL-C: -11.5 mg/dL    HDL-C: no sig dif   
                                                                       SF                    C- 151.1 mg           (5.9%)\1\             (grps)             
    Levin et al.   Base: 8-wk Step 1; Tx: 16-  PSY: 30 (26 men)       10.2 g/d bulk         SAT fat: PSY- 6.7%;   CHOL: -13 mg/dL       CHOL: 0; LDL-C -    
    (Ref. 19)       wk Step 1+supplement       Pla: 28 (23 men)        laxative, cellulose   C- 6.3%               (5.6%)                2.2%;              
                                                                      PSY: 7 g  CHOL: PSY- 166 mg; C- LDL-C: -13 mg/dL      HDL-C:              
                                                                       SF                     135 mg               (8.6%)                +6%    
                                                                                                                                         (sig from PSY)     
    Stoy et al.    4-wk Step 1; Step 1 +       23 men                 Estimated 11.6 g/d    SAT fat: PSY: 5.1%    CHOL: -10 mg/dL (4%)  HDL-C: No sig dif   
    (Ref. 23)       (8x5x5 wks): Grp 1: PSY-                           PSY from cereal:      (Grp 1) and 5.1%     LDL-C: -11 mg/dL       (grps)             
                    Pla-PSY; Grp 2: Pla-PSY-                           8 g SF;   (Grp 2)               (6%)                                     
                    Pla                                                Wheat cereal:        Wheat: 4.5% (Grp 1)                                             
                                                                       3 g SF    and 5.0% (Grp 2)                                               
                                                                                            CHOL: PSY 141-165 mg                                            
                                                                                            Wheat: 164 mg (Grp                                              
                                                                                             1), 117-170 (Grp 2)                                            
    Stoy et al.    4-wk Step 1; Step 1 +       22 men                 Estimated 11.6 g/d    SAT fat: PSY: 4.8     CHOL: -10 mg/dL (4%)  HDL-C: No sig dif   
    (Ref. 24)       (8x5x5 wks): Grp 1: PSY-                           PSY from cereal:      (Grp 1) and 5.2%     LDL-C: -11 mg/dL       (grps)             
                    Pla-PSY; Grp 2: Pla-PSY-                           8 g SF;   (Grp 2)               (6%)                                     
                    Pla                                                Wheat cereal:        Wheat: 4.7% (Grp 1)                                             
                                                                       3 g SF    and 5.6% (Grp 2)                                               
                                                                                            CHOL: PSY 155-163 mg                                            
                                                                                            Wheat: 133 mg (Grp                                              
                                                                                             1), 169-172 (Grp 2)                                            
    
    [[Page 8121]]
    
                                                                                                                                                            
    Wein-          Base: 12 wk Step 1; Tx: 8   23 (16m, 7f)           10.2 g/d bulk         SAT fat: PSY- 8.7%;   CHOL: -9 mg/dL        HDL-C: sig higher in
    gand et al.     wk Step 1+supplement,                              laxative, cellulose   C- 9%                 (3.8%)                PSY group          
    (Ref. 26)       crossover                                         PSY: 7 g  CHOL: PSY- 162 mg; C- LDL-C: -11 mg/dL                          
                                                                       SF                     203-261 mg           (6.2%)\1\                                
    Jenkins et     Base: 2 mo controlled Step  Study 1:               Study 1:              Study 1:              Study 1:              Study 1:            
     al.            2 diets; Tx: 2- 1 mo Step  32 (15m, 17f)          11.4 g/d PSY in       SAT fat: PSY- 4.6%;   CHOL: -27 mg/dL\1\    CHOL: -13.6 (5%)\2\ 
    (Ref. 30)       2 diets+ cereal,                                   cereal                C -4.6%               (9.8%)               LDL-C: -10 (5.5%)   
                    crossover                                          (7.8 g   CHOL: PSY- 31 mg; C-  LDL-C: -24 mg/dL\1\   HDL-C: -2 (3.3%)    
                                                                       SF), wheat bran       29 mg                 (12.6%)                                  
                                                                                            MUFA: PSY- 6%; C- 6%  HDL-C: -6.6 mg/dL                         
                                                                                                                   (11.3%)\1\                               
                                               Study 2:               Study 2:              Study 2:              Study 2:              Study 2:            
                                               27 (12m, 15f)          12.4 g/d PSY in       SAT fat: PSY- 6%; C-  CHOL: -34 mg/dL\1\    CHOL: -29.5         
                                                                       cereal                6%                    (12.6%)               (10.7%)\2\         
                                                                       (8.4 g   CHOL: PSY- 22 mg; C-  LDL-C: -27.9 mg/      LDL-C: -17 (9%)\2\  
                                                                       SF), wheat bran       22 mg                 dL\1\ (14.9%)        HDL-C: -1.4 (2.6%)  
                                                                                            MUFA: PSY- 12%; C-    HDL-C: -4.3 mg/dL\1\                      
                                                                                             12%                   (8%)                                     
    --------------------------------------------------------------------------------------------------------------------------------------------------------
    \1\ Significant differences between treatment and placebo groups unless otherwise indicated.                                                            
    \2\ Significant change across the diet phase.                                                                                                           
    
    
                          Abbreviations Used in Table 1                     
    C                                Control                                
    CHOL                             Blood total cholesterol                
    d                                Day                                    
    E                                Energy                                 
    g                                Gram                                   
    grp                              Group                                  
    HDL-C                            High density lipoprotein cholesterol   
    LDL-C                            Low density lipoprotein cholesterol    
    m/f                              Number of males, number of females     
    mg/dL                            Milligrams per deciliter               
    Pla                              Placebo                                
    PSY                              Psyllium                               
    Sat fat                          Saturated fat                          
    SF                               Soluble fiber                          
    Sig Dif                          Statistically significant difference   
    Step 1                            30% kcals fat, < 10%="" kcals="" sat="" fat,="">< 300="" mg="" cholesterol="" tdf="" total="" dietary="" fiber="" tx="" treatment="" wk="" week="">                     Approximately                          
    %                                Percent                                
                                                                            
    
    [FR Doc. 98-4074 Filed 2-12-98; 4:18 pm]
    BILLING CODE 4160-01-F
    
    
    

Document Information

Effective Date:
2/18/1998
Published:
02/18/1998
Department:
Food and Drug Administration
Entry Type:
Rule
Action:
Final rule.
Document Number:
98-4074
Dates:
This regulation is effective February 18, 1998. The Director of the Office of the Federal Register approves of the incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of certain publications in 21 CFR 101.81(c)(2)(ii)(B), effective February 18, 1998.
Pages:
8103-8121 (19 pages)
Docket Numbers:
Docket No. 96P-0338
PDF File:
98-4074.pdf
CFR: (14)
21 CFR 101.14(a)(2)
21 CFR 101.14(b)(3)(ii)
21 CFR 101.81(c)(1)
21 CFR 101.81(c)(2)
21 CFR 101.81(c)(2)(ii)
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