[Federal Register Volume 60, Number 139 (Thursday, July 20, 1995)]
[Proposed Rules]
[Pages 37507-37549]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-17505]
Federal Register / Vol. 60, No. 139 / Thursday, July 20, 1995 /
Proposed Rules
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[[Page 37507]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR PART 101
[Docket No. 95P-0003]
Food Labeling: Health Claims; Sugar Alcohols and Dental Caries
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
authorize the use, on food labels and in food labeling, of health
claims on the association between sugar alcohols and the nonpromotion
of dental caries. In addition, FDA is proposing to exempt sugar
alcohol-containing foods from certain provisions of the health claims
general requirements regulation. FDA is proposing these actions in
response to a petition filed by the National Association of Chewing Gum
Manufacturers, Inc., and an ad hoc working group of sugar alcohol
manufacturers (hereinafter referred to as the petitioners).
DATES: Written comments by October 3, 1995. The agency is proposing
that any final rule that may issue based upon this proposal become
effective 30 days following its publication.
ADDRESSES: Written comments to the Dockets Management Branch (HFA-305),
Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr., Rockville,
MD 20857.
FOR FURTHER INFORMATION CONTACT: Joyce J. Saltsman, Center for Food
Safety and Applied Nutrition (HFS-165), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-205-5916.
SUPPLEMENTARY INFORMATION:
I. Background
A. The Nutrition Labeling and Education Act of 1990
On November 8, 1990, the President signed into law the Nutrition
Labeling and Education Act of 1990 (the 1990 amendments) (Pub. L. 101-
535). This new law amended the Federal Food, Drug, and Cosmetic Act
(the act) in a number of important ways. One of the most notable
aspects of the 1990 amendments was that they confirmed FDA's authority
to regulate health claims on food labels and in food labeling. As
amended by the 1990 amendments, section 403(r)(1)(B) of the act (21
U.S.C. 343(r)(1)(B)) provides that a product is misbranded if it bears
a claim that characterizes the relationship of a nutrient to a disease
or health-related condition, unless the claim is made in accordance
with the procedures and standards contained in regulations adopted by
FDA.
Under section 403(r)(3)(B)(i) of the act, the Secretary of Health
and Human Services (and, by delegation, FDA) shall promulgate
regulations authorizing such claims only if he or she determines, based
on the totality of publicly available scientific evidence (including
evidence from well-designed studies conducted in a manner which is
consistent with generally recognized scientific procedures and
principles), that there is significant scientific agreement, among
experts qualified by scientific training and experience to evaluate
such claims, that the claim is supported by such evidence.
Section 403(r)(3)(B)(ii) and (r)(3)(B)(iii) of the act describes
the information that must be included in any claim authorized under the
act. The act provides that the claim shall be an accurate
representation of the significance of the substance in affecting the
disease or health-related condition, and that it shall enable the
public to comprehend the information and understand its significance in
the context of the total daily diet. Finally, section 403(r)(4)(A)(i)
of the act provides that any person may petition FDA to issue a
regulation authorizing a health claim.
The 1990 amendments, in addition to amending the act, directed FDA
to consider 10 substance-disease relationships as possible subjects of
health claims.
B. FDA's Response
In the Federal Register of January 6, 1993 (58 FR 2478), FDA
adopted a final rule that implemented the health claim provisions of
the act. In that final rule, FDA adopted Sec. 101.14 (21 CFR 101.14).
The regulation sets out the circumstances in which a substance is
eligible to be the subject of a health claim (Sec. 101.14(b)), adopts
the standard in section 403(r)(3)(B)(i) of the act as the standard that
the agency will apply in deciding whether to authorize a claim about a
substance-disease relationship (Sec. 101.14(c)), sets forth general
rules on how authorized claims are to be made in food labeling
(Sec. 101.14(d)), and establishes limitations on the circumstances in
which claims can be made (Sec. 101.14(e)). The agency also adopted
Sec. 101.70 (21 CFR 101.70), which establishes a process for
petitioning the agency to authorize health claims about a substance-
disease relationship (Sec. 101.70(a)) and sets out the types of
information that any such petition must include (Sec. 101.70(d)). These
regulations became effective on May 8, 1993.
In addition, FDA conducted an extensive review of the evidence on
the 10 substance-disease relationships listed in the 1990 amendments.
FDA has authorized claims that relate to 8 of these 10 relationships.
The present rulemaking on sugar alcohols and dental caries
represents the first rulemaking that FDA has conducted in response to a
health claim petition.
C. History of Sugar Alcohol Labeling
In a set of findings of fact and a tentative order on label
statements for special dietary foods that the agency issued on July 19,
1977 (42 FR 37166), FDA addressed the issue of the use of the terms
``sugar free,'' ``sugarless,'' and ``no sugar.'' The agency stated that
consumers may associate the absence of sugar in a product with weight
control and with foods that are low calorie or that have been altered
to reduce calories significantly. At that time, FDA viewed foods
intended to be useful in maintaining or reducing calorie intake or body
weight as foods for special dietary use, that is, as foods intended for
supplying particular dietary needs that exist by reason of a physical,
physiological, pathological, or other condition.
Evidence had been introduced at a public hearing in the 1977
rulemaking to show that the ``sugarless'' claim is useful to identify
foods like chewing gum, which is in sustained contact with the teeth,
in which the use of a sweetener other than a fermentable or cariogenic
carbohydrate may not promote tooth decay. The secretary of the American
Dental Association's Council on Dental Therapeutics supported the
importance of advertising and labeling sugarless chewing gum and mints
as noncariogenic, in the sense that they did not contribute to the
development of dental caries (Ref. 80).
In the final rule on label statements for special dietary foods
published in the Federal Register of September 22, 1978 (43 FR 43248),
FDA required a statement that a food is not low calorie or calorie
reduced (unless it is in fact, a low or reduced calorie food) when a
``sugar free,'' ``sugarless,'' or ``no sugar'' claim is made for the
food. The agency decided to allow ``useful only in not promoting tooth
decay'' as an alternative statement to accompany such claims. The
agency stated that the statements that the food is not low calorie or
not useful for weight control, as well as ``useful only in not
promoting tooth decay,'' were needed because the
[[Page 37508]]
term ``sugar free'' meant only that the food was sucrose free. A
``sugar free'' food could contain other fermentable carbohydrates.
Thus, the information about the effect of sugar alcohol-containing
foods on the risk of developing dental caries was originally placed on
the food label primarily to clarify that the product was not
necessarily useful in weight control, not to highlight the effect of
sugar alcohol on dental caries production.
In the Federal Register of November 27, 1991 (56 FR 60421), in
response to the 1990 amendments, FDA published a proposed rule entitled
``Food Labeling: Nutrient Content Claims, General Principles,
Petitions, Definition of Terms'' (the nutrition labeling general
principles proposal). In that document, FDA recognized that
developments in nutrition science had established that the focus of
nutrient content claims for providing dietary guidance had shifted from
special populations with particular conditions to the general
population (see 56 FR 60421). Therefore, in the nutrition labeling
general principles proposal, FDA proposed to treat several claims that
had been subject to regulation in Sec. 105.66 (21 CFR 105.66) as
special dietary use claims as nutrient content claims for the general
population. To eliminate redundancy in the regulations and to conform
Sec. 105.66 to the 1990 amendments, FDA proposed to define these claims
in part 101 (21 CFR part 101) and to remove them from part 105 (21 CFR
part 105). Specifically, FDA proposed to adopt definitions for terms
such as ``low calorie'' and ``reduced calorie,'' for other comparative
calorie claims, and for sugar claims under section 403(r)(2) of the act
and to codify them in Sec. 101.60. It also proposed to delete these
claims from Sec. 105.66.
In the Federal Register of January 6, 1993 (58 FR 2302), FDA
published its final rules on nutrient content claims. FDA adopted
definitions for claims for the calorie content of foods in Sec. 101.60
(58 FR 2302 at 2415). FDA defined claims regarding the sugars content
of a food, e.g., ``sugar free,'' ``free of sugar,'' ``no sugar,'' in
Sec. 101.60(c). In addition, FDA published a final rule that deleted
these claims from Sec. 105.66 (58 FR 2427).
However, based on its consideration of comments on the use of the
statement ``useful only in not promoting tooth decay'' to qualify the
``sugarless'' claim, FDA concluded that the statement was actually an
unauthorized health claim (58 FR 2302 at 2326). The claim is a health
claim because it characterizes the relationship of a substance (sugar
alcohols) to a disease (dental caries).
In the nutrient content claim general principles proposal (56 FR
60421 at 60437), the agency stated that it intended to reevaluate the
usefulness of chewing gums sweetened with sugar alcohols in not
promoting tooth decay. The agency stated that the data supporting the
claim were over 20 years old and requested that new data be submitted
in accordance with the final rule on health messages. In the nutrient
content claim final rule, FDA stated that it had received data on the
validity of a claim about this nutrient-disease relationship, and that
it would make a determination on whether to authorize a claim in
accordance with the final rule on health claims (58 FR 2302 at 2326).
On February 5, 1993, under the procedure established in section
701(e) of the act (21 U.S.C. 371(e)), a group of sugar alcohol
manufacturers submitted an objection to the revocation of
Sec. 105.66(f) (Ref. 2) and asked for a hearing on their objection. At
the same time, the group petitioned for reconsideration of the agency's
decision and for a stay of any administrative action by FDA pursuant to
the determination announced in the preamble of the nutrient content
claims rules that ``useful only in not promoting tooth decay'' is an
unauthorized health claim.
Filing objections to the revocation of Sec. 105.66(f) stayed the
effect of the final rule as a matter of law. FDA's response to these
objections and to the petitions is set forth elsewhere in this issue of
the Federal Register.
In the Federal Register of August 18, 1993 (58 FR 44036), FDA
published technical amendments to the health claim regulations in
response to comments that the agency received on the implementation
final rule that was published with the other final rules that responded
to the 1990 amendments in January of 1993 (see 58 FR 2066, August 18,
1993). One of the comments stated that if a petition were submitted for
the claim ``Useful Only in Not Promoting Tooth Decay,'' virtually none
of the sugar-free products on the market would be eligible to bear the
claim based on the requirements of a subsection of health claims
general principles regulation, Sec. 101.14(e)(6). FDA acknowledged that
certain food products of limited nutritional value that have been
specially formulated relative to a specific disease condition, such as
dental caries, may be determined to be appropriate foods to bear a
health claim (58 FR at 44036). The agency commented that it was its
intention to deal with such situations within the regulations
authorizing specific health claims. Therefore, FDA amended
Sec. 101.14(e)(6) to state that:
Except for dietary supplements or where provided for in other
regulations in part 101, subpart E, the food contains 10 percent or
more of the Reference Daily Intake or the Daily Reference Value for
vitamin A, vitamin C, iron, calcium, protein, or fiber per reference
amount customarily consumed prior to any nutrient addition.
II. Petition for the Noncariogenicity of Sugarless Food Products
Sweetened With Sugar Alcohol
A. Background
On August 31, 1994, the petitioners submitted a health claim
petition to FDA requesting that the agency authorize a health claim on
the relationship of sugar alcohols (i.e., xylitol, sorbitol, mannitol,
maltitol, lactitol, isomalt, hydrogenated starch hydrolysates, and
hydrogenated glucose syrups) in sugarless foods to dental caries (Ref.
1). On September 15, 1994, FDA sent the petitioners a letter stating
that study reports that are needed to support the petition, and that
are required for a health claim petition under Sec. 101.70, were not
included in the petitioners' submission. The agency stated that no
further action would be taken until that information was received (Ref.
3).
On September 27, 1994, the petitioners filed an amendment to their
petition submitting the required information. On October 7, 1994, the
agency sent the petitioners a letter acknowledging receipt of the
additional information and stating that the agency had begun its
scientific review of the petition (Ref. 4).
In this document, the agency will consider whether a health claim
on the relationship between sugar alcohols and dental caries is
justified under the standard in section 403(r)(3)(B)(i) of the act and
Sec. 101.14(c) of FDA's regulations. In addition, the agency will
consider the petitioners' request that the agency provide in any
regulation authorizing a claim that foods sweetened with sugar alcohols
be exempt from the requirement in Sec. 101.14(e)(6). The following is a
review of the health claim petition.
B. Preliminary Requirements
1. The Substances That Are the Subjects of the Petition
Sugar alcohols are a class of organic compounds that contain chains
of carbon atoms that bear two or more hydroxyl groups and have only
hydroxyl functional groups (Ref. 1). The hydroxyl groups replace ketone
or aldehyde groups that are found in sugars (Sec. 101.9(c)(6)(iii)).
The specific sugar alcohols that are the subject of this petition are
xylitol, sorbitol, mannitol,
[[Page 37509]]
maltitol, maltitol syrup, maltitol solution, isomalt, lactitol, and
mixtures of sugar alcohol substances, i.e., hydrogenated glucose syrup
(HGS) and hydrogenated starch hydrolysate (HSH) products.
Xylitol is a monosaccharide polyhydric alcohol with a 5-carbon
backbone. It occurs naturally in fruits (e.g., plums, strawberries, and
raspberries) and vegetables (e.g., cauliflower and endive) (Refs. 82
and 83). Xylitol is made commercially by the hydrogenation of D-xylose.
Sorbitol is a monosaccharide polyhydric alcohol with a 6-carbon
backbone. It is found naturally in many types of berries and fruits and
in seaweeds and algae (Ref. 82). Sorbitol is made by hydrogenation of
glucose.
Mannitol is also a 6-carbon, monosaccharide polyhydric alcohol. It
occurs widely in nature in plants (e.g., pumpkins, mushrooms, onions,
beets, celery, and olives), algae, and fungi. Like sorbitol, mannitol
is made commercially by the hydrogenation of glucose.
Maltitol is a disaccharide alcohol (4-D-glucopyranosyl-D-sorbitol)
with a 12-carbon backbone. It is produced commercially by hydrogenation
of maltose.
Lactitol is also a disaccharide alcohol (-D-
galactopyranosyl D-sorbitol) with a 12-carbon backbone. It is produced
by hydrogenation of lactose (Ref. 84).
HSH and HGS are mixtures of sugar alcohols manufactured by
hydrogenation of corn starch or glucose syrups. The composition of the
sugar alcohols in the final product will depend on the manufacturing
process. Therefore, HSH and HGS products from different manufacturers
may contain different proportions of the same sugar alcohols. One HSH
product, under the trade name ``Lycasin,'' was first produced in Sweden
by hydrogenation of potato starch. The Swedish product contained a
mixture of sorbitol, maltitol, maltotrititol, and hydrogenated
dextrines of various molecular weights. When the manufacturing process
was moved to France in the 1970's, the production process was also
changed (Ref. 85). The French product, ``Lycasin 80/55,'' was made from
the hydrogenation of corn starch and contained 6 to 8 percent sorbitol,
50 to 55 percent hydrogenated disaccharides, 20 to 25 percent
trisaccharides, and 10 to 20 percent hydrogenated polysaccharides (Ref.
75). Lycasin 80/55, or HSH 80/55, is less fermentable and produces less
acid than the Swedish product (Ref. 85).
Isomalt, also known by the commercial name ``Palatinit,'' is an
equimolar mixture of the disaccharide alcohols of -D-
glucopyranosyl-D-sorbitol and -D-glucopyranosyl-D-mannitol.
It is produced by treating sucrose with enzymes, followed by
hydrogenation of the resulting mixture.
2. The Substances are Associated With a Disease for Which the U.S.
Population is at Risk
Dental caries is recognized in The Surgeon General's Report on
Nutrition and Health (Surgeon General's report) as a disease or health-
related condition for which the United States population is at risk
(Ref. 7). The overall prevalence of dental caries imposes a substantial
burden on Americans. Of the 13 leading health problems in the United
States, dental diseases rank second in direct costs (Ref. 7).
Based on this fact, FDA tentatively concludes that sugar alcohols
meet the requirement in Sec. 101.14(b)(1).
3. The Substances Are Food
Sugar alcohols are used as replacements for simple and complex
sugars as sweeteners and bulking agents in foods (Ref. 1). Thus sugar
alcohols are consumed for their taste and for their effect as a
stabilizer and thickener (21 CFR 170.3(o)(28)). Therefore, FDA
tentatively concludes that these substances satisfy the preliminary
requirements of Sec. 101.14(b)(3)(i).
4. The Substances Are Safe and Lawful
Several of the sugar alcohols that are the subject of this
proceeding are currently listed in FDA's food additive and generally
recognized as safe (GRAS) regulations, i.e., xylitol (21 CFR 172.395),
mannitol (Sec. 180.25 (21 CFR 180.25)), and sorbitol (Sec. 184.1835 (21
CFR 184.1835)). Moreover, GRAS affirmation petitions have been
submitted for each of the remaining substances, i.e., maltitol (GRASP
6G0319), maltitol syrups (HGS syrups) (GRASP 3G0286), isomalt (GRASP
6G0321), lactitol (GRASP 2G0391), HSH (GRASP 5G0304) and HSH syrups
(GRASP 1G0375).
The agency notes that these GRAS affirmation petitions are under
consideration and that any positive action resulting from this proposed
rule should not be interpreted as an indication that the agency has
affirmed those uses of the sugar alcohols as GRAS. Such determinations
can only be made after the agency has completed its review of the GRAS
petitions. A preliminary review of the GRAS affirmation petitions
reveals that they contain significant evidence supporting the safety of
these substances.
The agency also points out, however, that some concerns about the
safety of sugar alcohols do exist. For example, in a filing notice for
the affirmation of the GRAS status of lactitol (58 FR 47746, September
10, 1993), FDA stated that ``the agency's notice of filing of GRASP
2G0391 should not be interpreted either as a determination, preliminary
or otherwise, that the issue of Leydig cell tumors has been resolved or
that lactitol qualifies for GRAS affirmation.'' Also, by notice in the
Federal Register of December 13, 1994 (59 FR 64207), the agency
announced the filing of a food additive petition (FAP 4A4412) to amend
the interim food additive status of mannitol to permit an alternate
method of manufacture. In this notice, the agency pointed out concerns
about data from studies on mannitol that demonstrate a significant
incidence of benign thymomas, and an abnormal growth of thymus gland
tissue, in female rats fed mannitol. In addition, the safety of sugar
alcohols has been examined by the Federation of American Societies for
Experimental Biology (FASEB) (Ref. 90), as well as internationally by
the Joint Expert Committee on Food Additives (Ref. 91). The agency also
notes that two of the sugar alcohols that are listed in FDA's food
additive and GRAS regulations, i.e., mannitol (Sec. 180.25) and
sorbitol (Sec. 184.1835), require a warning label regarding laxation if
daily consumption of these sugar alcohols is expected to exceed 20
grams (g) per day for mannitol and 50 g per day for sorbitol. Nothing
in this proposal alters these requirements.
Based on the totality of the evidence, the agency is not
challenging, at this time, the petitioner's position that the use of
sugar alcohols is safe and lawful. Although FDA tentatively concludes
that the petitioner has satisfied the requirements of
Sec. 101.14(b)(3)(ii), the agency requests comments on its tentative
conclusion.
III. Review of Scientific Evidence
A. Introduction
The development of dental caries is the result of an interaction
between sugars (and other fermentable carbohydrates, such as refined
flour) and oral bacteria in a suitable environment (Ref. 71).
Microorganisms, and Streptococcus mutans (S. mutans) in particular, in
dental plaque metabolize available dietary sugars, producing acid and
sticky polysaccharides that adhere to the tooth as plaque. Acid
produced from rapid and complete fermentation of sugars creates an acid
environment within the
[[Page 37510]]
plaque, characterized by a pH of usually less than 5.0, that is capable
of demineralizing tooth enamel and causing a carious lesion.
Studies designed to measure the cariogenicity of a food assess the
potential to cause caries if it is consumed in a standard way by a
highly susceptible subject (Ref. 8). The methods used to measure
cariogenic potential include long-term controlled human caries trials,
in vivo and in vitro plaque pH measurement, demineralization and
remineralization techniques, and rat caries models (Refs. 8 through
11). Because long-term clinical caries trials are difficult to conduct,
an integration of the plaque pH, animal caries, and demineralization
methodologies has been recommended as the best measure for establishing
the cariogenic potential of a food (Ref. 12). Experts recommend,
however, that these methods be used with appropriate controls, such as
sucrose, to assess experimental results (Ref. 13).
Plaque acidity studies are useful in providing evidence on the
effects of many microbial and physiological factors on the cariogenic
potential of foods (Ref. 78). An acidic plaque environment at the tooth
surface, specifically a pH of less than 5.5, suggests microbial
fermentation of a substrate resulting in microbial growth, plaque and
acid production, and promotion of carious lesions from enamel
decalcification. Factors that can modify these effects include the
presence of promoters or inhibitors in food products that affect
bacteria growth, the nature of the acids produced as a result of
bacterial metabolism of food carbohydrates (Ref. 78), intraplaque
buffering, and the pH of mixed saliva (Ref. 74).
B. Review of Scientific Evidence
1. Evidence Considered in Reaching the Decision
The petitioners submitted scientific evidence on the various sugar
alcohols and their effects on plaque, plaque pH, and dental caries.
This evidence included human (in vivo and epidemiological), animal, and
in vitro studies regarding the association between consumption of sugar
alcohols from chewing gum and other foods and plaque pH, acid
production, plaque quantity and quality, bacteria levels, and the
incidence of caries. The petition included four tables that summarized
the information for: (1) Human plaque and demineralization, (2)
bacteriological studies, (3) animal experiments, and (4) human
longitudinal and field studies. A fifth table provided a summary of
review articles.
In addition to the information submitted by the petitioner, the
agency considered other studies and reviews, such as the reports on
health aspects of sugar alcohols by the Life Sciences Research Office
(LSRO) and the FASEB (Refs. 14 through 16). The agency also considered
the results of additional human epidemiological studies on caries
incidence and demineralization; studies of animal caries; and in vitro
plaque pH studies.
2. Criteria for Selection of Human Studies
The criteria that the agency used to select pertinent studies were
that the studies: (1) Present data and adequate descriptions of study
design and methods; (2) be available in English; (3) provide daily
intakes of the sugar alcohol or enough information to estimate their
daily intakes; (4) include in vivo or in vitro assessment of the
changes in plaque pH or plaque acid production; (5) for intervention
studies on caries development, be of no less than 2 years (yr) in
duration; and (6) be conducted in persons who generally represent the
healthy United States' population (adults or children).
In selecting human studies for review, the agency decided that only
those studies investigating the use of sugar alcohols in chewing gums
and other foods, including mouth rinses that would be representative of
beverages, were appropriate for review. The agency excluded studies
that were published in abstract form because they lacked sufficient
detail on study design and methodologies, and because they lacked
necessary primary data. In selecting animal and in vitro studies for
review, the agency chose those studies that measured caries
development, plaque pH, or acid production from plaque bacteria.
3. Criteria for Evaluating the Relationship Between Sugar Alcohols and
Human Dental Caries
The subject of the petitioned health claim is the nonpromotion of
dental caries by sugar alcohol-containing foods, especially chewing gum
and confectioneries. To support this claim, there needs to be
significant scientific evidence to show that the sugar alcohol or sugar
alcohol mixture, e.g., HSH, makes no contribution to the progression of
dental carious lesions in humans. It would be difficult, if not
impossible, to design and execute a study that would directly address
this issue because such a study would require a control group that
consumed foods containing no sugars, fermentable carbohydrates, or
sugar alcohols.
In the absence of studies that directly evaluate the nonpromotion
of dental caries by sugar alcohol-containing foods, the agency gave the
greatest weight to those studies that evaluated in vivo the acidogenic
potential of plaque and plaque pH of sugar alcohols and sucrose in
representative food systems (e.g., confectioneries and solutions).
These in vivo measures can provide specific information about the
effect of sugar alcohols in the oral environment and, more
specifically, about the effect of sugar alcohols on pH at the interface
between dental plaque and tooth surfaces. The more acidic the
environment on the tooth surface, the greater the chance for enamel
demineralization and caries formation.
The agency also considered in vitro studies that measured plaque pH
and acid production of sugar alcohols in solution, and long-term caries
trials that evaluated caries development in a population using foods
containing sugar alcohols and sucrose. Studies investigating in situ
the demineralization or remineralization of enamel as a result of the
action of sugar alcohols on human dental plaque were considered as
supporting evidence by the agency.
C. Human Studies
1. Evaluation of Human Studies
FDA evaluated the results of studies against general criteria for
good experimental design, execution, and analysis. The criteria that
the agency used in evaluating these studies included appropriateness of
subject selection criteria; adequacy of the description of the
subject's oral health before intervention; extent of evaluation of
subject's type of dental plaque (i.e., sticky or nonsticky, thick or
thin); methods of plaque collection; adequacy of methods used to assess
study endpoints (e.g., in vivo versus in vitro assessment of plaque
pH); and other study design characteristics, including randomization of
subjects, appropriateness of controls, report of attrition rates
(including reasons for attrition), frequency of snack or substance
consumption, recognition and control of confounding factors (for
example, the subject's use of fluoride during the test period), and
appropriateness of statistical tests and comparisons. The agency also
considered it desirable if information on treatment and control diets,
the sugar alcohol content of the test substance, and daily sugar
alcohol and nutrient intakes was available.
[[Page 37511]]
A review of the studies evaluating the effect of sugar alcohols on
plaque pH and acid production and of the in vitro microbiological
studies is provided in Table 1. Table 2 provides a review of
epidemiological studies evaluating the incidence of dental caries and
studies on demineralization and remineralization.
2. Summary of Evidence Relating Sugar Alcohol and Plaque pH or Acid
Production
Bibby and Fu (Ref. 38) measured human plaque pH in vitro using 0.1-
, 1.0-, or 10-percent solutions of the following sweeteners: Sucrose,
HSH, mannitol, isomalt, xylitol, isomaltulose, sorbose, saccharin, and
aspartame. Results showed the lowest plaque pH was attained with
sucrose (1- and 10- percent solution: pH less than 5.0). Plaque pH
decreased with increasing concentrations of isomalt, sorbitol,
mannitol, and HSH. The lowest pH attained for isomalt was about 5.6,
for sorbitol 5.82, for mannitol 5.22, and for HSH about 5.0. Negligible
acid production was measured from aspartame, saccharin, and xylitol.
Solution mixtures of xylitol (5 to 20 percent) and sucrose (10 percent)
were fermented to the same low pH as sucrose alone. Thus, the presence
of xylitol in a sucrose and xylitol mixture did not affect acid
production in plaque from sucrose.
The results of this study support the contention that xylitol does
not promote dental caries by lowering plaque pH below 5.5. However, the
results for sorbitol, mannitol, isomalt, and HSH do not support a
``nonpromotion'' claim. The results suggest that when higher
concentrations of these sweeteners are present in food, the plaque pH
may reach a level that will promote decalcification of dental enamel.
Birkhed and Edwardsson (Ref. 39) measured plaque pH and acid
production of human plaque samples in solutions of mannitol, xylitol,
maltitol, sorbitol, French HSH, Swedish HSH, fructose, and glucose
syrups. Results showed that plaque pH in the presence of xylitol,
maltitol, mannitol, and French HSH increased or slightly decreased from
baseline (pH remaining at 6.8 or above). Sorbitol showed a slight
decrease in plaque pH, but the final pH attained was about 6.0. The
other sweeteners, including Swedish HSH, depressed plaque pH below pH 6
over the 30-min (min) test period. The results of this study showed
that mannitol and xylitol produced no plaque acid compared to sucrose.
Maltitol and sorbitol produced plaque acid at rates that were 10 to 30
percent of that of sucrose. French HSH produced 20 to 40 percent and
Swedish HSH 50 to 70 percent of the acid produced by sucrose.
Birkhed et al. (Ref. 40) measured acid production in vitro and
plaque pH changes in vivo over a 30-min period following a 30-second(s)
mouth rinse with 10-percent glucose or sorbitol solutions. To determine
whether plaque microorganisms can adapt to the presence of sorbitol,
i.e., use it as a source of energy like sucrose, with repeated exposure
to the sugar alcohol, investigators measured plaque pH and acid
production at the end of a 6-week (wk) period. During the 6-wk period,
each subject rinsed their mouth six times per day for approximately 2
min at a time with a 10-percent sorbitol solution. At the end of 6 wk,
plaque pH was again measured for a 30-min period following a mouth
rinse with glucose and sorbitol. The study results showed acid
production in the presence of sorbitol, before adaptation, to be 11.3
percent of that from glucose. After the adaptation period, plaque acid
production from sorbitol increased to 30 percent of the glucose rate.
After the adaptation period to sorbitol, the glucose rinse produced
mean plaque pH values that were higher than before the adaptation
period. The differences in plaque pH, however, were only significant at
2 and 5 min following the rinse.
Overall results of this study suggest that sorbitol produces very
little plaque acid. Mean plaque pH values after sorbitol adaptation in
the presence of the 10-percent sorbitol rinse showed only a slight
decrease from the baseline value. The differences in mean plaque pH,
compared to baseline, at 5, 10, 20, and 30 min following the rinse were
significant. The authors noted that the fermentability of sorbitol was
more pronounced after the adaptation period than before.
Birkhed et al. (Ref. 41) studied the effects on in vivo plaque pH
and in vitro acid production from HSH (Swedish HSH), maltitol,
sorbitol, and xylitol. Subjects in each group sucked on two lozenges a
day, containing 0.5 g of one of the four sweeteners and 0.5 g of gum
arabic, four times daily between meals (total of eight lozenges per
day) for 3 months (mo). Changes in plaque pH over a 30-min period were
measured in each of the sugar alcohol groups after a 30-s mouth rinse
with a 50-percent solution containing the same sweetener as the
lozenge. The rinse was used 1 wk before and 1 wk after the lozenge
period. A control group consumed no lozenges but rinsed with each of
the four sweeteners. At least 1 wk separated each mouth rinse
experiment. Acid production activity (APA) from dental plaque suspended
in glucose and each of the four sugar alcohols was determined 1 wk
before and 1 wk after the 3-mo consumption period.
The results with HSH showed that although plaque pH values differed
before and after the lozenge period, differences were not statistically
significant, and that the lowest plaque pH attained was above 6.0. In
the maltitol group, plaque pH before the lozenge period was higher than
the pH following the lozenge period. Differences at 2, 10, and 30 min
were statistically significant. However, there were no significant
differences in plaque pH at any time compared to baseline. The lowest
plaque pH recorded was about 6.9. Plaque pH in the xylitol group
changed very slightly, remaining around pH 7. Plaque pH in the sorbitol
group was higher before than after the lozenge period. Differences in
pH at times 0 to 20 min and 0 to 30 min before compared with after the
test period were statistically significant (p<0.05). Final plaque pH
values after the 30-min test period were between 6.7 and 7.0. There
were no significant differences in plaque pH between the test and
control groups using any of the test rinses.
Comparing the APA results for each sweetener with those for glucose
showed that HSH was 56 percent of that of glucose 1 wk before the
lozenge period and 59 percent of that of glucose 1 wk after the lozenge
period. The APA for maltitol compared to glucose was 26 percent
(before) and 32 percent (after), sorbitol was 15 percent (before) and
18 percent (after), and xylitol was 0 percent at both time periods.
Differences before and after each 3-mo lozenge period were not
statistically significant for any of the sugar alcohols.
The results of this study suggest that even though there is some
acid production from HSH, maltitol, and sorbitol, the effect on plaque
pH in vivo is not detrimental to tooth enamel.
Frostell (Ref. 42) evaluated the effect on plaque pH of sugar
solutions and different types of candy and foods. Although the focus of
this study was not sugar alcohols, the investigators used sorbitol and
HSH as a comparison to sucrose in some of the experiments. Plaque was
collected prior to the test period, and its pH was determined. Subjects
then rinsed with a test solution or ate a piece of candy or other food
being tested. Plaque was collected after 2, 5, 10, 20, and 30 min and
its pH was again measured. Sweeteners tested included a sucrose rinse
(concentrations from 0.05 to 50 percent), sorbitol tablets (2 g
sorbitol), sugar tablets (containing
[[Page 37512]]
glucose and sucrose), HSH candy, sugar candies (with sucrose, dextrose,
and maltose), marmalades (60-percent HSH or sucrose), and sugar-
sweetened sponge cakes, ginger cakes, marshmallows, and chocolates.
Results with the sucrose rinses showed that plaque pH decreased with
increasing concentrations of sucrose.
Comparing the effects on plaque pH between the sorbitol and sucrose
candies results showed that in the sorbitol group's plaque pH increased
from about 6.5 (baseline) to 6.9 before returning to baseline. Plaque
pH decreased in the sucrose group from 6.5 (baseline) to about 6.0.
After 10 min, the pH in the sucrose group slowly increased to about
6.3. Differences in plaque pH between the sorbitol candy and sucrose
candy groups were significant at all time periods. In the HSH candy
group, plaque pH was significantly higher than that in the group
consuming sucrose candy. Differences were significant at all time
periods. The lowest plaque pH in the HSH group was above pH 6.3. The
group consuming marmalade with HSH experienced a drop in plaque pH to
about 6.0 (from 7.0) after 5 min, followed by a gradual increase to a
final pH of about 6.5. The group consuming sucrose marmalade
experienced a plaque pH of about 5.3 after 5 min, followed by a gradual
increase in pH to about 6.0.
Toors and Herczog (Ref. 43) evaluated in vivo plaque pH and in
vitro fermentability of an experimental (nonsucrose) licorice in a
pooled plaque-saliva mixture. Fermentability (i.e., acid production) of
the test substrates was expressed as a percentage of the sucrose
licorice. Plaque was collected from 12 volunteers on the day after they
consumed 10 pieces of the candy. In vivo plaque pH was measured during
and after consumption of licorice by means of pH telemetry. Substrates
used in the above tests included sucrose licorice, the experimental
licorice, components of the experimental licorice (including sorbitol,
potato starch derivative, soy flour, and others), xylitol, hydrogenated
potato starch (HPS) (a type of HSH), and a white bread suspension.
Results showed the fermentability of the test substrates to be as
follows: Potato starch derivative (82 percent), soy flour (75 percent),
sorbitol (12 percent), experimental licorice (68 percent), xylitol (5
percent), HPS (60 percent), and white bread suspension (79 percent). In
vivo plaque pH results showed sucrose licorice with a minimum plaque pH
of about 5.0, experimental licorice with a minimum plaque pH of about
5.5, and a sucrose rinse with a plaque pH of about 4.5.
The results of this study show that food ingredients like soy flour
can contribute to the cariogenicity of a food regardless of the
presence of a sugar alcohol.
Gallagher and Fussell (Ref. 44) compared the in vitro
fermentability of xylitol and other sugar alcohols with sucrose in
dental plaque. Plaque collected from adults and children of different
ages was incubated in broth culture. Acid production was measured as
pH. The control media contained no added carbohydrates.
The results of acid production measurements showed that sucrose was
significantly more acidogenic compared to the control and xylitol.
Differences were significant. There was no significant difference in
acid production between the control groups and the xylitol groups.
Gehring and Hufnagel (Ref. 45) described intra- and extraoral pH
measurements of dental plaque. Six adult men and women rinsed for 2 min
using one of seven test substances followed by intraoral plaque pH
measurements after 3, 4, 5, 7, 9, 13, 17, 21, 27, and 32 min. For the
extraoral test, visible plaque was removed, suspended in distilled
water, and the pH measured at 3, 5, 7, 9, 11, 15, and 25 min after
subjects rinsed with test substances. Test substances included 20
percent solutions of glucose, sucrose, fructose, HSH, mannitol,
isomalt, sorbitol, sorbose, or xylitol.
The results of the intraoral plaque pH measurements showed only
slight pH decreases within 5 min after administration of xylitol and
mannitol, with a return to baseline measures at the end of the 32-min
test period. Sorbitol, HSH, isomalt, and sorbose reached a minimum pH
just below 6.0 after 5 min followed by a slight increase to about pH
6.1 to 6.4 at the end of the test period. Sucrose, glucose, and
fructose showed a minimum pH value of about 4.6 to 4.7 (after 5 min)
with an increase to about pH 5.3 to 5.5 at the end of 32 min. Minimum
plaque pH by extraoral measurements were higher than the pH according
to intraoral measurements. Sucrose, glucose, and fructose minimum pH
values ranged from about 5.0 to 5.7 after 5 min and increased to about
5.6 to 6.0 after 32 min. Other pH values were not given. The authors
attribute the differences in intra- and extraoral plaque pH
measurements to methods in handling plaque removal and the influence of
saliva substances.
Havenaar et al. (Ref. 46) evaluated in vitro acid formation from
oral bacteria in the presence of sugar substitutes and the influence of
xylitol on glucose in growing cultures of S. mutans. Fresh isolates of
Streptococci and other strains were obtained from caries free and
caries active subjects. Acid production in 1-percent solutions of
glucose (control), sorbose, sorbitol, xylitol, lactitol, maltitol, and
HSH was determined by incubating the sweetener in phenol red broth
containing oral bacteria. A color change indicated acid formation.
Changes in pH was measured after subculturing S. mutans in each of the
sweeteners, after frequent subculturing in each sweetener to obtain
adapted strains of S. mutans, and after subculturing the adapted
strains once in glucose and resubculturing in the sweetener. Growth of
S. mutans and pH measurements were also measured in a glucose broth
with and without added xylitol.
The results showed no acid production from xylitol or sorbose and
acid production from sorbitol, lactitol, and HSH. The authors stated
that S. mutans slowly fermented maltitol. Results also showed no change
in pH with xylitol and a moderate drop in pH to about 6 to 6.5 (actual
values not given) with maltitol, sorbitol, lactitol, and HSH after 120
min. Adaptation by S. mutans to the sweeteners resulted in a marked
increase in fermentation, with final pH values dropping to about 4.5 to
5.5. After one subculturing of the adapted strain in glucose, S. mutans
lost most of its ability to ferment the sweeteners. The addition of
small amounts of xylitol to glucose broth somewhat inhibited acid
production from S. mutans, but it had no effect on final pH attained.
Jensen (Ref. 47) measured interproximal plaque pH in subjects using
five different HSH's and sorbitol and sucrose as controls. Four
subjects rinsed with a 5 milliliter (mL) portion of the test solution
for 60 min. Plaque pH was then monitored for 30 min. Following the pH
measurements, the subject rinsed their mouth with distilled water and
chewed paraffin for about 5 min to bring oral pH back to resting
levels. The test was repeated with each subject using each of the four
test solutions.
The results showed that plaque pH for all test substances remained
above pH 6.0 over the 30-min test period. Plaque pH using the sorbitol
rinse was similar to that using the test substances. Using the sucrose
rinse resulted in plaque pH measurements of approximately 4.0 to 4.1.
The identity of the test substances was not provided in this
unpublished study. Results indicate that the HSH solutions used in this
study were
[[Page 37513]]
significantly less acidogenic than sucrose and no different than
sorbitol.
Maki et al. (Ref. 48) compared acid production in vivo from
isomaltulose, sorbitol, xylitol, and sucrose (control) in human dental
plaque. Dental plaque was collected from 12 individuals and incubated
with phosphate buffer. After endogenous acid production was measured, a
1-percent solution of the test substance in the same buffer was added,
and acid production measured again.
The results showed no acid production in the presence of xylitol.
Compared to sucrose (100-percent acid production), acid production from
sorbitol was 1 percent. The authors noted that the percent acid
production from sorbitol may vary considerably among individuals and
with the amount of exposure to sorbitol.
Park et al. (Ref. 49) measured interproximal plaque pH in five
subjects after consuming one of three snacks alone or one of three
snacks followed by a single mint containing sorbitol (94 percent) or a
sorbitol and xylitol blend (79 percent and 15 percent, respectively).
When mints were used, they were consumed 3 min following ingestion of
the sweet snack. Snacks tested included a sandwich cookie, cupcake, and
granola bar. A randomized block design was used to administer the test
products and mints (see Table 2 for further details). The lowest plaque
pH attained after consuming the three test products without mints
ranged from 4.02 to 4.16. When the sorbitol mint was consumed following
the test product, mean plaque pH values increased and ranged from 4.68
to 5.04. When the sorbitol and xylitol mint was consumed following
consumption of the test products, mean plaque pH increased to a range
of 5.32 to 5.60. Differences in mean plaque pH values between the mint
products differed significantly when the mints were used after the
granola bar and cupcake challenges. There was no significant difference
in mean plaque pH between the sorbitol (5.04) and the sorbitol and
xylitol mint (5.60) products when these products were used after the
sandwich cookie challenge.
The results show that consumption of a sugarless mint reduced the
acidogenicity of the test snacks, although final pH values remained
below pH 5.5 in all but one test. The authors attributed the results of
this study to the stimulatory effects on salivary flow by sugar
alcohols. Increasing salivary flow increases the buffering capacity of
saliva, thus reducing the acidogenic potential of a variety of snack
foods. The authors also attributed the additional buffering effects of
the sorbitol and xylitol mint to the presence of xylitol and its
potential benefits in reducing plaque microbial activity. Without a
sucrose-containing mint as a comparison, however, the influence of
sugar alcohols on saliva production cannot be adequately assessed.
Soderling and coworkers (Ref. 50) investigated the effect on dental
plaque of chewing gums that contained either xylitol, sorbitol, or a
mixture of xylitol and sorbitol and compared the results with those
obtained with subjects who used sucrose gums. Twenty-one subjects
(adults, ages 19 to 35 yr) who were not habitual gum chewers were
randomly assigned to chew gum containing either xylitol, sorbitol, or a
blend of the two sugar alcohols for 2 wk. Subjects chewed 10 pieces of
gum per day for an intake of either 10.9 g xylitol, 10.9 g sorbitol, or
10.9 g xylitol and sorbitol (8.5 g xylitol and 2.4 g sorbitol). The
control group was made up of seven habitual sucrose gum users. Subjects
maintained their usual diets and oral hygiene except just before to
clinic visits. Interdental plaque pH was collected, and the resting
plaque pH determined. Plaque pH was measured at 2, 5, 10, 15, and 20
min after an oral rinse containing the same sugar alcohols as used in
the gum. Afterward, subjects rinsed with water and chewed a piece of
paraffin for 1 min to expedite removal of sugar alcohols from the
mouth. Baseline pH was again measured, followed by a mouth rinse with
10 mL of 10-percent sucrose. Plaque pH was again determined.
The results from using gum for 2 wk showed no significant changes
in resting plaque pH in the xylitol and xylitol and sorbitol groups,
whereas the use of sorbitol gum was associated with a lower pH. Final
plaque pH values after use of sorbitol gum were significantly lower
than baseline values, but all final values remained above pH 6.0.
Birkhed and Skude (Ref. 51) evaluated, among other tests, the APA
from glucose, soluble starch, and Swedish HSH in dental plaque. Eleven
adults were instructed to avoid oral hygienic procedures for 2 days. No
dietary changes were required. At the end of 2 days, plaque was
collected. The APA was determined from 3-percent solutions of glucose,
boiled soluble starch, and HSH. The APA was also determined in
increasing concentrations (0.003 to 12 percent weight per volume (w/v))
of starch and HSH.
The results showed significantly lower (p<0.001) APA from soluble
starch (75.7 percent) and HSH (61.5 percent) compared to glucose (99.7
percent). The APA from HSH was also significantly lower (p<0.01) than
that from soluble starch. The range of optimum acid production for both
substrates was 0.03 to 6 percent. The authors noted that Swedish HSH is
more fermentable than French HSH, which contains less high molecular
weight hydrogenated saccharides than Swedish HSH.
Grenby et al. (Ref. 76) evaluated the dental properties of lactitol
compared to five other bulk sweeteners, i.e., sucrose, glucose,
sorbitol, mannitol, and xylitol, in vitro using a standardized mixed
culture of dental plaque microorganisms. Sweeteners were incubated for
24 hours (h) in media containing a 1-percent solution of one of the six
sweeteners. Plaque microorganisms were also incubated in media
containing the sweeteners with segments of intact surfaces or with
segments of pulverized dental enamel. The demineralization action of
the acid produced by microbial fermentation was assayed by calcium and
phosphorous analyses.
The greatest amount of acid production and lowest pH (significantly
different than the sugar alcohols) were reported with sucrose and
glucose (pH of 4.0 to 4.3). Lactitol and xylitol showed only slight
changes in pH and acid production over the 24 h (final pH of 6.1 to
6.3); whereas sorbitol and mannitol showed slight changes in pH during
the first 12 h (pH6), then gradually decreased to a final pH
of 4.6 to 5.1 after 24 h.
The results of the demineralization test showed highly significant
differences (p<0.001) between sucrose and glucose and the sugar
alcohols. The reductions in calcium and phosphorous dissolving in
sorbitol was approximately 80 to 85 percent, mannitol 63 to 69 percent,
and lactitol and xylitol 94 to 98 percent compared to mineral loss in
the presence of glucose.
3. Summary of Evidence Relating Sugar Alcohol and Dental Caries: Long-
Term Studies
Moller and Poulsen (Ref. 20) determined the effect of long-term
chewing of sorbitol chewing gum on the incidence of dental caries,
plaque, and gingivitis. The sorbitol chewing gum contained calcium
phosphate which acts as a buffer in saliva to help maintain pH and aid
remineralization. Two groups of children, ages 8 to 12 yr of age, from
two different schools in Denmark took part in this 2-yr study. Group 1
chewed one piece of sorbitol-containing gum three times a day, after
meals. Group 2 chewed no gum and
[[Page 37514]]
served as the control. At the start of the study, subjects in group 1
had more decayed and filled toothsurfaces than the control group;
however, the differences were not statistically significant.
The results showed that the sorbitol group had a significantly
lower incidence of dental caries compared to the control after 2 yr.
The control group, which did not chew gum, did not experience the same
salivary stimulation from the chewing of gum, nor did they have an
equivalent source of calcium phosphate. These are large confounders in
this study. The authors noted a number of factors that could contribute
to the observed results, such as the sorbitol content of the chewing
gum, reduced consumption of sugar-containing sweets, intra-examiner
variability, and other unknown conditions.
Banozcy et al. (Ref. 21) evaluated the effect of sorbitol-
containing sweets on the caries increment of children aged 3 to 12 yr,
in a clinical longitudinal study planned for 3 yr. The test group
consumed 8 g of sorbitol per day between meals, while the control group
consumed a similar amount of sucrose-containing sweets.
The results showed that mean decayed, missing, or filled (DMF)
values for teeth in the sorbitol group were 1.09, 0.90, and 1.18 in the
first, second, and third yr, respectively. The sucrose group had mean
DMF values of 2.61, 1.86, and 1.13 for the first, second, and third yr,
respectively. The differences in caries increments were significant
(p<0.001) in the first and second yr but not in the third yr. The
authors noted that the lack of significance in the third yr may be
attributed somewhat to a lack of subject compliance since the children
in the sorbitol group traded sweets with the sucrose group, in addition
to other factors. Results of this study indicate that sorbitol is less
cariogenic than sucrose.
Kandelman and Gagnon (Ref. 22) reported on the incidence and
progression of dental caries in school children after 12 mo of a 2-yr
study using xylitol in chewing gum. The subjects were 433 children,
ages 8 to 9 yr old, from 13 elementary schools, and were from low
socioeconomic areas with a high caries rate. The children were assigned
to one of three groups: A control group that received no chewing gum
and chewed no gum while at school, a test group that received gum
containing 15-percent xylitol and 50-percent sorbitol (XYL15), and a
second test group that received gum containing 65-percent xylitol
(XYL65). Students were not randomly assigned to groups. Rather, an
entire class was assigned to one of the three groups. The XYL65 group
consumed 3.4 g xylitol per day, and the XYL15 group consumed 0.8 g per
day.
The results showed significantly lower net progression of decay
(NPD) (i.e., the difference in the number of reversals from the
progressions of decay for each child) in the XYL65 group (1.25) than in
XYL15 group (1.87) (p< 0.05), and each xylitol group had significantly
(p<0.001) lower NPD than the control. The decayed, missing, filled
surfaces (DMFS) increment was also significantly lower in the xylitol
groups compared to the control. There was no significant difference in
DMFS between the gum groups. Results of this study suggest that chewing
gum containing xylitol or a blend of xylitol and sorbitol provided more
benefits for teeth than not chewing gum at all.
Rekola (Ref. 23) compared the progression of incipient carious
lesions on buccal smooth surfaces in subjects participating in the 2-yr
Turku sugar study (Ref. 24). Subjects consumed either a diet containing
sucrose or one with almost complete replacement of sucrose products
with xylitol-containing products. The progression of carious lesions
were assessed by use of color dental photographs of the right and left
sides and of the front of maxillary and mandibular teeth.
The results showed that the sucrose group had a significant
tendency for increased size of carious lesions over the 2-yr period
compared to the group consuming xylitol (p<0.01). The white spot
lesions in the xylitol group were significantly smaller than those in
the sucrose group.
Rekola (Ref. 25) quantified changes in the size of approximal
carious lesions in subjects after 2 yr of almost complete substitution
of dietary sucrose with xylitol (Ref. 23). Bitewing radiographs were
taken during the 2-yr study. In this study, the radiographs were
projected onto a planimetry plate so that the area of the lesions could
be determined. The sizes of the lesions at the different time periods
were compared, and the rate of caries progression was also compared. At
the beginning of the study, there was no difference in the mean size of
carious lesions between groups. The size of the approximal lesions,
i.e., lesions that were neither filler nor overlapping at 0 and 24 mo,
in the sucrose group increased significantly (p<0.001) over 2 yr
compared to the lesions in the xylitol group. The lesion size in the
xylitol group remained virtually unchanged.
The authors reported a trend towards decreasing lesion size in
canines and first molars compared to molars and second premolars in the
xylitol group. This trend was not observed in the sucrose group.
Results of these studies support the observation that xylitol is less
cariogenic than sucrose.
In a World Health Organization (WHO) field trial in Hungary (Ref.
26), the effects of a partial substitution of sucrose for xylitol in
the diets of 689 institutionalized children, ages 6 to 11 yr, were
examined. The xylitol group used fluoride dentifrice and consumed no
more than 20 g of xylitol per day in chewing gum, chocolate, hard
candy, and wafers. The fluoride group received fluoride in dentifrice,
water, and milk, but consumed no xylitol products. The control group
received no fluoride treatment and consumed no xylitol-containing
products. After 3 yr, the xylitol group had a statistically significant
(p<0.001) lower incidence of caries compared to the control and
fluoride groups. The authors noted that results from this study were
obtained under conditions where caries prevalence and incidence were
still high. Results of this study support the observation that xylitol-
containing products are less cariogenic than sucrose-containing
products.
In a 2-yr substudy (Ref. 28) of the WHO xylitol field studies in
Hungary (Ref. 26), Scheinin and coworkers assessed the caries increment
with systemic fluoride (fluoride group) and restorative treatment only
(control group). This study differed from the 3-yr study primarily in
baseline differences. Children entering the institutions during the
first yr of the 3-yr study were included in this substudy.
The substudy showed similar favorable results with xylitol compared
to the control. The caries increment was 3.8 in the xylitol group, 4.8
in the fluoride group, and 6.0 in the control group. The differences in
caries increment between the xylitol group and the other two groups
were significant (p<0.001). Results again supported a lower incidence
of caries when xylitol is substituted for sucrose in the diet.
In a WHO field trial in Thailand and French Polynesia (Ref. 29),
the usefulness of a fluoride rinse, fluoridated sucrose chewing gum,
and fluoridated xylitol (51 percent) and sorbitol gum in controlling
dental caries was evaluated in children over a 3-yr period. In French
Polynesia, a fourth group used nonfluoridated chewing gum sweetened
with xylitol (51 percent) and sorbitol. Approximately 250 children at
each of the ages 6 to 7 yr, 9 to 10 yr, and 12 to 13 yr were examined.
The 12- to 13-yr age group was intended to provide data for
[[Page 37515]]
comparison with the 9- to 10-yr old group, who would be ages 12 to 13
yr at the end of the study.
The results from the Thailand study showed that the fluoridated
xylitol and sorbitol gum group had lower decayed, missing, and filled
teeth (DMFT) and DMFS scores than either the fluoride rinse group or
the fluoridated sucrose gum group. Results from the French Polynesia
study showed that the subjects started with much higher DMFT and DMFS
mean scores initially than the subjects in Thailand. Although the
results with the fluoride gum sweetened with the sugar alcohols were
better than any of the other treatments, the overall caries incidence
in this population is very high. The presence of fluoride in the
chewing gums confounds the results of the sugar alcohols. The authors
describe this study population as a community experiencing an increase
in the prevalence of the disease. This study group does not reflect the
general population of the United States.
In another WHO field trial, Kandelman and coworkers (Ref. 30)
evaluated the effects of xylitol intervention on dental caries in
French Polynesian children, ages 7 to 12 yr. Of 746 subjects enrolled
in this 32-mo study, 468 completed the study. Subjects in the xylitol
groups consumed 20 g of xylitol daily in various food products, such as
chewing gum, hard candy, chocolate, and gumdrops. The control group
received no xylitol-containing products.
The results showed significantly reduced caries increment rate by
37 percent to 39 percent in the xylitol groups compared to the
controls. This study was neither randomized nor blinded. Results
support the observation that xylitol-containing products are less
cariogenic than the sucrose-containing products.
Frostell and coworkers (Ref. 31) determined the effect on caries
increment in children, ages from 2\1/2\ to 4 yr, of substituting HSH
for sucrose in candy. During this 1\1/2\- to 2\1/2\-yr study, subjects
in the test group consumed candies made with HSH and chewing gum made
with sorbitol. The control group consumed sucrose candies and gum.
Investigators monitored the intake of candies by use of coupons which
the parents used at local stores to buy the candy. An analysis of the
coupons used showed that parents of the children in the test group used
a smaller number of coupons than the parents of the children in the
control group. Based on inquiries, the investigators discovered that
the parents of the subjects in the HSH group had also given the
children other candy in addition to HSH candy. The consumption of HSH
candy was reported from 50 to 75 percent of the total candy
consumption.
The results showed no significant differences in caries scores
after 1\1/2\ to 2\1/2\ yr with HSH candy consumption compared to
sucrose candy consumption. When investigators analyzed the data of
those children whose parents consumed the correct candy for their
group, the differences in caries increment between the groups were
still not significant but showed a trend towards a lower incidence of
caries in the HSH group. The results of this study were confounded by
poor compliance, inter-examiner variability, lack of blinding, and
inconsistent results and do not support significant dental benefits
from the use of HSH.
Glass (Ref. 32) evaluated the cariogenicity of sorbitol chewing gum
with regular use by children, ages 7 to 11 yr old, living in a
nonfluoride area. In this 2-yr study subjects were randomly assigned to
either a no-chewing group (control) or to the one which chewed gum
twice daily. Subjects in the gum group were provided two sticks of gum
daily for use at school and four sticks of gum for use at home when
school was not in session.
The results showed that over the 2-yr study period, mean caries
increments were 4.6 new decayed and filled (DF) surfaces for the
sorbitol gum group (n=269) and 4.7 new DF surfaces for the no-gum group
(n=271). The difference between the groups was not statistically
significant. Although the results of this study suggest that adding
sorbitol-containing gum to the diet did not result in any additional
dental caries, the effect of chewing gum per se on the incidence of
dental caries was not considered.
4. Summary of Evidence Relating Sugar Alcohol and Dental Caries: Short-
Term Studies
Ikeda et al. (Ref. 33) evaluated the cariogenicity of maltitol and
a polysaccharide alcohol using an intraoral cariogenicity test (ICT)
and rat tests. Most of the details of the methods used in the ICT were
not provided, making the results difficult to interpret. Bovine enamel
fragments were extraorally dipped in 3-percent solutions of sucrose
(control), maltitol, or the polysaccharide alcohol for 1 min every day.
After 1 wk, hardness was measured. The higher the value for hardness
means a softer enamel and a greater loss of enamel.
The results showed a decalcification score for maltitol of 1.66
compared to a score of 2.70 for sucrose. These differences were
significant. In the animal study, one group was provided a feed with
26-percent maltitol and 30-percent starch, a second group was provided
a feed with sucrose instead of maltitol, and a third group consumed a
diet without sucrose. Results showed a caries score of 45.8 for the
sucrose group, 3.2 for the maltitol group, and 5.2 for the no-sucrose
group. Differences between the sucrose group and the other groups were
statistically significant.
Yagi (Ref. 34) evaluated the effects of maltitol on changes in
enamel hardness. Enamel decalcification was measured using an ICT with
a denture containing two bovine enamel slabs. Four subjects wore the
dentures for 7 days. Each day, one enamel slab was exposed to a 3-
percent maltitol solution and the other to a 3-percent sucrose
solution. Enamel hardness was measured at the end of the wk.
The results showed that the average change in hardness compared to
pretreatment levels for the enamel in maltitol was 1.47 micrometers
compared to 3.35 micrometers for the enamel in sucrose. Differences
between the two measurements were significant. The authors noted that
there were considerable differences in individual responses to sucrose
and maltitol. They attributed these differences to the oral environment
(e.g., plaque bacteria and quality and quantity of saliva). However,
general observations were that sucrose causes significant loss of
enamel, as evidenced by changes in enamel hardness, compared to the
effect of maltitol on tooth enamel.
Leach et al. (Ref. 35) evaluated in situ the effect on
remineralization of artificial caries-like lesions in human enamel with
sorbitol. Ten adult subjects wore cast bands containing enamel on one
lower first molar tooth for two 3-wk periods during which they
continued to use normal oral hygiene procedures. Artificial caries
lesions were made in each enamel slab and covered with gauze to
encourage the formation and accumulation of plaque on the enamel
surface. Subjects were given snack foods (chocolate bar, raisins,
cream-filled wafers, and cream-filled, iced cupcake) and instructed to
consume one each morning and afternoon between meals. During the first
experimental period, subjects chewed, for 20 min each, five sticks per
day of commercial sugarless gum after meals and snacks. The gum was
sweetened primarily with sorbitol and small amounts of mannitol, HGS,
and aspartame. During the second experimental period, snacks were
consumed but without chewing gum (control).
[[Page 37516]]
The results showed statistically significant (p<0.001)
remineralization during both experimental periods compared to the
original lesion. The difference between the remineralization with and
without gum was also significantly different (p<0.01), indicating
overall promotion of remineralization by gum chewing. The authors
attributed the remineralization during the nongum period to the
presence of gauze used with the intraoral device to collect plaque. The
gauze could have concentrated calcium and phosphates from the diet in
plaque and fluoride from dentifrice. It is not known what effects the
duration and timing of the gum chewing had on the results. Without a
comparison to sucrose-containing gum and a nonsweetened gum, it is not
possible to evaluate the effect of chewing gum for 20 min.
Rundegren et al. (Ref. 36) evaluated in situ the effect on
demineralization of sucrose substitutes in a 4-wk test. Intraoral
devices containing bovine enamel mounted on acrylic blocks were used
with group 1. Partial dentures with enamel slabs were used with group
2. Sweeteners tested included 10 percent solutions of sucrose,
maltitol, and HSH. Sucrose was used as the positive control, and 0.9-
percent solution of sodium chloride was used as a negative control.
Subjects immersed the test sites of their appliances in the test
sweetener four times a day for a 10-min period. Plaque was collected at
the end of 4 wk and plated to determine the content of S. mutans. The
degree of demineralization was measured by evaluating changes in
microhardness of the enamel. The buffering capacity of whole saliva was
evaluated weekly by measuring final pH in a mixture of 1 mL of saliva
and 3 mL of sodium chloride.
The results showed a higher degree of demineralization overall in
the adults (ages 56 to 59 yr) using the partial dentures compared to
students (age 19 yr) using an intraoral device. Results from the test
(n=4) of enamel microhardness in HSH versus sodium chloride suggest
that HSH does not contribute to demineralization, and that measured
changes in microhardness reflected the background of fermentable
carbohydrates in the diet. Comparing the differences in microhardness
of enamel slabs between the sucrose and HSH diets and the sucrose and
maltitol diets showed that sucrose results in significant
demineralization compared to the sugar alcohols.
Creanor et al. (Ref. 37) evaluated the effect of chewing gum for 20
min on in situ enamel lesion remineralization compared to a fluoridated
dentifrice. Artificial enamel lesions were created in vitro in sound
human enamel and mounted for wearing just opposite the lower first and
second molars. Baseline mineral contents were measured. Subjects used a
fluoridated dentifrice twice daily and maintained their regular diets.
Six subjects chewed five sticks of chewing gum containing sorbitol and
some HGS and aspartame after each meal and snack. The gum was chewed
for 20 min in order to minimize any deleterious effects of sucrose. Six
other subjects received no gum and served as the control. At the end of
7 wk, the test subjects became the control group, and the control
subjects became the new test group. The new test group then chewed
sucrose-containing gum for 7 wk.
The results showed that after using sugar-free gum for 7 wk, the
degree of mineral loss for the enamel corresponded to a
remineralization value of 18.2 percent. After 7 wk of chewing sucrose
gum, the percent remineralization was calculated to be 18.3 percent.
The difference between the sorbitol and sucrose gum groups was not
significant. Results of this study suggest that chewing gum for 20 min,
regardless of the sweetener, can be beneficial to dental health.
A common problem in studies evaluating the dental health benefits
of sugar alcohol-containing chewing gum is the absence of an
appropriate control group. Most of the studies that have been done use
a control group that does not chew gum. Ideally, to evaluate the
relationship of sugar alcohol-sweetened chewing gum in not promoting
dental caries, the control group would chew an unsweetened gum product.
Such a group is needed to take into consideration the effects of
chewing gum itself on the endpoint measure, e.g., plaque pH or plaque
acid production. Chewing gum is known to stimulate saliva, which can
help neutralize oral acids, raise plaque pH, and help to promote enamel
remineralization in some circumstances. It would be considered
unethical by standards in the United States to use a control group that
chews sucrose-containing gum and, as a consequence, puts the subjects
at risk of dental disease, in order to compare the incidence of dental
caries to that from a sugar alcohol-containing gum.
The few long-term caries field trials that were submitted with this
petition show how multiple problems in the execution of clinical
studies can easily confound the results. Problems often include subject
compliance, reporting and control of dietary intake, selection of
appropriate control foods, inter- and intraexaminer variability,
subject attrition, and inability to blind the study. The majority of
these trials compared sucrose consumers to individuals who had partial
or complete substitution of sugar alcohols for sucrose. The results
consistently demonstrated significantly fewer caries in the group
consuming sugar alcohols than in the group consuming sucrose.
Although the relationship between some of the sugar alcohols and
promotion of dental caries has not been well studied in humans, it is
becoming increasingly evident that sugar alcohols, when substituted for
sucrose and other fermentable carbohydrates, may provide important
dental health benefits for the consumers of those products.
D. Animal Studies
FDA reviewed over 20 animal studies investigating the effects of
sugar alcohol consumption on the incidence of dental caries or on the
acidogenic potential of dental, S. mutans, or mixed oral
microorganisms. Most of the animal studies that have been done to test
the effect of sugar alcohols on the incidence of caries were programmed
feeding studies using weanling rats. The animals were usually divided
into groups and fed diets containing different test sweeteners. The
control diets were either a basal diet with no carbohydrate sweeteners
or sugar substitutes or a basal diet with added sucrose. The test diets
were administered over a period of weeks, increasing the sugar
substitute concentration slowly to allow the animals time to adapt to
the specific sweetener and to minimize the severity of diarrhea, a side
effect of sugar alcohol consumption that increases with increasing
concentration of the sugar alcohol.
Investigators also evaluated the general health and growth of the
animals during the experimental period. Many animals, and rats in
particular, do not like the taste of sugar alcohols and, therefore,
will eat less of the test diet and increase their intake of water. Most
investigators monitored the animals' total dietary intake to ensure
that consumption patterns were similar between the control and test
animals.
A potential confounding factor in these studies is the effect of
total food and water intake on caries development. If animals consume
less of a sugar alcohol diet compared to the control animals consuming
a sucrose diet, any significant differences in caries incidence may
actually be attributable to the differences in food and water
consumption and not to an effect of the sugar substitute. Some studies
reported a lower survival rate in animals on the
[[Page 37517]]
sugar alcohol diets. This finding made interpretation of the results
more difficult because of uneven group sizes.
In order to promote the cariogenic process, the animals were
inoculated with either mixed strains of plaque bacteria or purified
strains of S. mutans and other microorganisms found in dental plaque.
Experimental periods lasted, on the whole, for 60 to 70 days. These
periods included the time given for the animals to adapt to the test
diets.
Havenaar et al. (Ref. 52) fed S. mutans inoculated rats one of six
diets 18 times a day: The basal diet plus 50-percent starch, or the
basal diet plus 30-percent starch and 20 percent of either sucrose,
HSH's, xylitol, sorbitol, or L-sorbose. In a second experiment, the
rats were fed the same diets 14 times a day and alternated with the
basal diet containing 20-percent sucrose and 10-percent glucose (four
times a day). In both experiments, the starch, HSH, xylitol, and L-
sorbose groups showed significantly less fissure lesions than the
sorbitol and sucrose groups. The sorbitol group showed significantly
less fissure caries in the mandibular molars with respect to the
severity of the lesions compared to the sucrose group.
Havenaar et al. (Ref. 53) in five successive experiments, fed rats
ad libitum on diets containing sucrose or HSH 80/55. In each
experiment, the rats were inoculated with plaque from rats in the
previous experiment (Ref. 52). Results showed that compared to sucrose,
HSH was relatively noncariogenic. The incidence of fissure caries in
the mandibular molars for rats consuming 20-percent sucrose was 13.1,
whereas the fissure caries incidence in rats consuming 20-percent HSH
was 1.5 to 2.5 (p<0.001).
Havenaar et al. (Ref. 54) evaluated the usefulness of diets for
testing the caries promoting or inhibiting properties of sugar
substitutes. The investigators fed two groups of rats experimental diet
2000 containing 50-percent sucrose and 14-percent starch or 50-percent
sucrose, 9-percent starch, and 5-percent xylitol for a period of 42
days. Results showed no significant differences in caries incidence
between the sucrose starch, the xylitol group and the sucrose and
starch group. In another experiment animals were fed diet SSP 20/5
containing 20-percent sucrose, 5-percent glucose, and 25-percent starch
or 20-percent sucrose, 5-percent glucose, 20-percent starch, and 5-
percent xylitol for a period of 66 days. Results showed the xylitol,
sucrose, and starch group to have significantly fewer caries (12.3
caries versus 14.8) compared to the sucrose, starch, and glucose group.
Havenaar and coworkers (Ref. 55) fed one group of rats a basal diet
containing 20-percent sucrose, 5-percent glucose, and 25-percent
starch. The test group received the basal diet with 20-percent starch
and 5-percent xylitol and fluoride. After 54, 75, or 96 days, rats were
crossed over to the other diet for an additional 21 to 42 days. Results
showed that the xylitol group had significantly fewer fissure caries
than the sucrose group. The authors also reported that the longer the
experimental period, the more severe the caries, irrespective of the
presence of xylitol. After crossover, total numbers of caries did not
change, but the xylitol group showed significantly fewer initial
lesions compared with the mean caries incidence in the sucrose group on
day 54.
Grenby and Colley (Ref. 56) fed a control group of rats a
cariogenic diet containing 46-percent sucrose and fed two test groups
the same cariogenic diet either with 20 percent of the sucrose replaced
with xylitol, sorbitol, mannitol, or wheat starch (experiment A). The
animals consuming sorbitol and mannitol did not remain healthy during
the experiment, so this part of the experiment was terminated. The
animals consuming xylitol also experienced difficult health effects at
first but later improved and were returned to the 20-percent xylitol
diet. In experiment B there were only two diets: A cariogenic diet with
46-percent sucrose and an experimental diet with 10 percent of the
sucrose in the diet replaced with xylitol.
In experiment A, significantly fewer caries were experienced only
in the group consuming the sucrose and xylitol diet compared to the
control group. In experiment B, the level of caries was high for both
the sucrose group and the sucrose and xylitol group. The overall caries
scores were not significantly different.
Karle and Gehring (Ref. 57) evaluated the effect of sugar alcohols
and sucrose on both xerostomized (salivary glands removed) and
nonxerostomized rats. The control group consumed a basal diet without
sweetener. Test groups received the basal diet plus sucrose, xylitol,
isomalt, or other sweeteners. Sweetener concentrations were increased
over a 3-wk period to a level of 30 percent of the diet. The
xerostomized rats had more caries with all substances than the
nonxerostomized rats. Sucrose was shown to be the most cariogenic
sweetener, and xylitol the least cariogenic, in the nonxerostomized
rats. Both the xylitol and isomalt groups had significantly fewer
caries than the sucrose group.
Muhlemann and coworkers (Ref. 58) compared the cariogenicity of
diet 2000 (containing 64-percent wheat flour) to the same diet
containing xylitol or sorbitol (15 percent and 25 percent of the flour
replaced) or sucrose (15 percent and 25 percent of the flour replaced).
Sweetener mixtures containing 15-percent sucrose and 15-percent xylitol
or sorbitol and 25-percent sucrose and 25-percent xylitol or sorbitol
were also substituted for the flour ingredient of the basal diet. The
rats consuming diets with 15- and 25-percent sucrose experienced 17.3
and 17.8 smooth surface caries, respectively. Rats consuming animal
chow with 15-percent xylitol or sorbitol experienced 0.0 and 1.9 smooth
surface caries, respectively. The caries score for the control group
was 4.9. The highest number of fissure caries (11.3) occurred in the
25-percent sucrose group. The control group had 5.1 lesions.
Substituting xylitol (25 percent) in the diet resulted in fewer caries
(0.2) compared to the control, but differences were not significant.
Twenty-five percent sorbitol in the diet produced a caries score of
2.8.
Shyu and Hsu (Ref. 59) evaluated the cariogenicity of 10-percent
xylitol, mannitol, sorbitol, and sucrose in rats fed a plain basal
diet. A control group was fed the basal diet without sweetener. Caries
evaluations were made on the 45th and 90th days of feeding. The xylitol
group had 86 percent fewer caries (significant) compared to the sucrose
group and 76 percent fewer caries than the control. The mannitol group
experienced 70 and 51 percent fewer caries than the sucrose and control
groups, respectively. The sorbitol group experienced 48 and 14 percent
fewer caries than the sucrose and control groups, respectively.
Bramstedt et al. (Ref. 60) evaluated the cariogenicity of isomalt,
xylitol, and sucrose in 60 rats divided into five groups. The control
diet was a basic diet containing half synthetic feed. Another control
group received a special basic diet containing no low molecular weight
carbohydrates. The test groups received the basic diet with increasing
doses of sweetener up to 30 percent of the diet. The sucrose group had
a significantly higher number of caries than either of the sugar
alcohol groups. The group consuming the special basic diet had the
lowest incidence of caries. There were no significant differences in
the number of caries between the basic diet, xylitol, and isomalt
groups, although the isomalt group showed a slightly higher incidence
of caries.
Izumiya et al. (Ref. 61) fed rats 10 or 20 percent by weight of
sweeteners in
[[Page 37518]]
feed. Rats consuming a dietary feed containing 10-percent maltitol had
significantly fewer caries than the sucrose group. Details of this
study and the results were not given in this reference.
Gehring and Karle (Ref. 62) evaluated the cariogenic properties of
isomalt, in comparison to those of sucrose and xylitol in the basal
diet of conventional and gnotobiotic (i.e., specially reared laboratory
animals in which the microflora are specifically known) rats. The final
concentration of sweetener in the feed was 30 percent. A second
experiment was performed using isomalt, xylitol, sorbitol, and sucrose
in chocolate. The basal diet constituted 40 percent of the total diet,
and the chocolate constituted 60 percent. The isomalt group had
significantly fewer caries than the sucrose group, and the xylitol
group had significantly fewer caries than the isomalt group. The second
experiment showed significant differences in caries experience after
the T (initial caries lesions) and B (advanced caries) stages between
the sucrose and sorbitol chocolate groups, the sorbitol and isomalt
chocolate groups, and also between the isomalt and xylitol chocolate
group. The order of cariogenicity of the test substances was sucrose
greater than (>) sorbitol > isomalt > xylitol > control. An in vitro
microbiological experiment was performed to test acid production
capacity of plaque microorganisms in 10 percent solutions of isomalt,
glucopyranosido mannitol (GPM), glucopyranosido sorbitol (GPS),
sorbitol, mannitol, sucrose, and fructose. GPS and GPM are the two
components that make up isomalt. Sucrose produced acid rapidly and had
the greatest acid formation. Sorbitol and mannitol produced acid
slowly, and isomalt and its two components had practically no acid
production in vitro.
Karle and Gehring (Ref. 63) evaluated the cariogenicity of isomalt
in rats. Six groups of rats received the basic diet without low
molecular weight carbohydrates in addition to xylitol, sorbose,
isomalt, lactose, and sucrose. The control group received only the
basic diet. Sweetener concentrations were increased slowly up to 30
percent by weight of the basic feed. The highest number of fissure
caries were caused by sucrose (about 33) followed by lactose (25),
isomalt (about 13), sorbose (about 12), xylitol (about 7) and the
control (5). Differences in caries incidence between the sucrose and
the other groups were significant.
Larje and Larson (Ref. 64) fed rats a caries diet, diet 2000, to
which various sweeteners were added. The caries diet, containing 56
percent sucrose, was used as a control ration. Sucrose substitutes used
in at least one of the experiments included glucose, fructose,
mannitol, sorbitol, potato starch, starch/sucrose mixtures, or HPS
(contains sorbitol and hydrogenated dextrins). In the first experiment
each group was fed diet 2000 for a few days, then they were changed to
one of the diets containing a sucrose substitute. Each test diet was
fed for 7 out of every 14 days followed by rotation back to the control
diet. The diets were changed every 2 or 3 days according to a
predetermined schedule. A second experiment was designed to determine
the effect of feeding the sucrose diet after the period of bacterial
implantation on diets containing sucrose substitutes. The animals
consumed one of the test diets the first week while being inoculated
with S. mutans, followed in the final 7 wk by the control diet
containing sucrose. A third experiment was designed to determine the
effect of feeding sucrose and sucrose-substitute diets intermittently
after the period of bacterial implantation on the sucrose diet. The
animals consumed diet 2000 the first wk, followed in the final 7 wk by
diets containing the sugar substitutes.
The results of the first experiment showed significantly (p<0.001)
fewer smooth surface caries with all sugar alcohols, potato starch,
dextrose, and hydrogenated starch compared to the sucrose group.
Significantly (p<0.05) fewer sulcal caries were experienced in the
groups receiving mannitol, sorbitol plus starch, potato starch, and HPS
compared to the sucrose group. The authors observed that in all of the
experiments, every group in which sucrose was restricted, whether by
dietary substitution or by shortened feeding periods, developed
significantly fewer caries on smooth surfaces compared to the sucrose
control animals. The animals in the mannitol, sorbitol plus starch, and
sorbitol groups consumed less food during the test period compared to
the sucrose controls. The authors stated that food consumption and
weight gains were directly related to the incidence of caries.
The results of experiment 2 showed significantly (p<0.001) fewer
smooth surface caries in groups fed hydrogenated starch, potato starch,
dextrose, fructose, sorbitol plus starch, dextrose plus fructose
compared to the sucrose group. Groups receiving HPS, fructose, and
sorbitol plus starch experienced significantly (p<0.001) fewer sulcal
caries compared to the sucrose group.
The results of experiment 3 showed significantly (p<0.001) fewer
smooth surface caries in groups receiving potato starch, fructose,
sorbitol plus starch, dextrose plus fructose, dextrose, and
hydrogenated starch compared to the sucrose group. The overall results
showed that reducing the exposure to sucrose results in fewer carious
lesions.
Muhlemann (Ref. 65) tested the effects of topical applications of
sugar substitutes on caries incidence and bacterial agglomerate
formation in rats receiving a cariogenic diet containing 20-percent
sucrose. Sweeteners tested (50 percent w/v) included the following:
Sucrose, mannitol, GPS, GPM, isomalt, sorbitol, maltitol, and French
HSH. Three control groups were used: (1) One group received the
cariogenic diet (20-percent sucrose) and no topical applications, (2)
the second group received a topical application of water with the
cariogenic diet, and (3) the third group was treated topically with
chlorhexidin digluconate (0.5 percent) as a positive control. Topical
solutions were applied five times a day for 23 days.
Among the carbohydrates treatments, the isomalt, GPS, and GPM
groups had the lowest incidence of fissure and smooth surface caries.
The differences, however, between the caries incidence in these three
groups and the other test groups were not statistically significant.
The incidence of caries in the chlorhexidine control group was
statistically significantly lower than all treatment groups. The
control groups receiving no application and water both experienced
slightly more caries than the sugar alcohol groups. Results of these
studies suggest that in the presence of a cariogenic diet, topical
application of mannitol, isomalt, sorbitol, maltitol, or HSH does not
affect the promotion by sucrose of dental caries in rats.
Ooshima et al. (Ref. 66) evaluated the cariogenicity of maltitol in
rats infected with S. mutans. Animals were divided into 12 groups.
Group A received a control diet containing 56-percent wheat flour.
Groups B through L received the same diet as the control group but had
portions of the wheat flour replaced with one of the test substances.
The sweeteners tested were as follows: 10-percent maltitol plus 46-
percent wheat flour (group B), 20-percent maltitol plus 36-percent
wheat flour (group C), 10-percent sucrose plus 46-percent wheat flour
(group D), 10-percent sucrose plus 10-percent maltitol plus 36-percent
wheat flour (group E), 20-percent sucrose plus 36-percent wheat flour
(group F), 20-percent sucrose plus 20-percent maltitol plus
[[Page 37519]]
16-percent wheat flour (group G), 24-percent sucrose plus 32-percent
wheat flour (group H), 24-percent sucrose plus 16-percent maltitol plus
16-percent wheat flour (group I), 28-percent sucrose plus 28-percent
wheat flour (group J), 28-percent sucrose plus 12-percent maltitol plus
16-percent wheat flour (group K), or 40-percent sucrose plus 12-percent
wheat flour (group L).
The results of this study showed that the maltitol did not induce
dental caries in groups B and C compared to the wheat flour alone
(group A). Groups A, B, and C experienced significantly (p<0.001) fewer
caries than the sucrose group (group L). Groups D through I and K
reported significantly (p<0.001 and p<0.01, respectively) fewer caries
than group L. There was no significant difference in caries score
between group J (equal parts sucrose and wheat flour) and group L.
Thus, this study suggests that replacing sucrose with less cariogenic
sweeteners or wheat flour results in fewer dental caries in rats.
Tate et. al. (Ref. 67) reported on the correlations between
progressive caries and sugar intake in hamsters inoculated with S.
mutans. Animals were fed a diet with 10-percent sucrose (group 1), 20-
percent sucrose (group 2), 10-percent sucrose plus 10-percent maltitol
(group 3), 10-percent sucrose plus 10-percent coupling sugar (group 4),
10-percent maltitol (group 5), or 10-percent coupling sugar (group 6).
Group 2 experienced the most caries. There was no significant
difference in caries score between group 1 and groups 3 and 4. Groups 5
and 6 had significantly (p<0.01) fewer caries than groups 1 or 2. This
reference did not provide sufficient details regarding the methodology
and analysis of results for purposes of evaluating the weight of the
results.
Leach and Green (Ref. 68) fed two groups of rats a basal diet
supplemented with sucrose plus 3-percent xylitol or 6-percent xylitol.
The control group consumed the basal diet with sucrose. In experiment
1, rats were continuously fed the same diet during the experimental
period. In experiment 2, rats were fed diets alternating between the
control diet one day and the test diet the next day. In experiment 1,
rats fed the sucrose and 6-percent xylitol mixture had significantly
(p<0.02) fewer fissure caries than the control. There were no
significant differences in the xylitol mixture groups. In experiment 2,
both xylitol mixture diet groups had significantly (p<0.001) fewer
fissure caries than the control. There were no significant differences
among the xylitol mixture groups.
Mukasa (Ref. 69) evaluated the cariogenicity of maltitol and SE58
in rats. Product SE58 is a highly purified corn starch treated with
enzyme and hydrogenated. It contains 20- to 25-percent sorbitol, 20- to
30-percent maltitol, 15- to 25-percent maltotrititol, and 30- to 40-
percent maltopentaitol. In experiment one, three groups of rats were
fed diet 2000 containing either 56-percent sucrose, maltitol, or SE58,
among other ingredients. Because the rats consuming the maltitol and
SE58 diets experienced serious growth problems, experiment one was
discontinued. In experiment two, the level of all sweeteners in diet
2000 was reduced to 26 percent, with the remaining 30 percent as added
corn starch. The sucrose group had a mean fissure caries score of 31.5
and a smooth surface caries score of 14.1. The maltitol group had 3.1
fissure caries and no smooth surface caries. The SE58 group had 4.6
fissure caries and 0.5 smooth surface caries. Differences between the
sucrose group and each sugar alcohol group were significant.
Van der Hoeven (Ref. 70) evaluated the cariogenicity of isomalt in
rats. Test diets consisted of a base diet containing 16-percent sucrose
and 44-percent wheat flour and a base diet with 16-percent isomalt and
44-percent wheat flour. The control diet consisted of 60-percent wheat
flour and no added sweetener. Diets were offered ad libitum over a
period of 14 wk. Results showed increasing incidence of dentinal
fissure lesions in the sucrose group (wk 2 = 4; wk 14 = 14 lesions) and
almost no caries in the isomalt group (wk 2 = 0; wk 8 = 4; wk 14 = 1
lesion). There was no difference in the incidence of caries between the
isomalt and the control groups.
Van der Hoeven (Ref. 73) evaluated the cariogenicity of lactitol in
program-fed rats. The sweetener was incorporated into a powdered diet,
described by Havenaar et al. (Ref. 54), consisting of a basic part (50
percent), wheat flour (25-percent), and test substance (25-percent).
Lactitol was compared with sorbitol, xylitol, sucrose, and a control
with wheat flour in addition to the basic part. The animals received 9
g of diet divided into 18 portions of 0.5 g each per day. The animals
on the xylitol and sorbitol diets were reported to experience reduced
weight gains and a reduced appearance of the fur. None of the animals
suffered from diarrhea.
There were significantly fewer caries in the xylitol, lactitol,
sorbitol, and wheat flour groups compared to the sucrose group. The
incidence of caries in the lactitol and sorbitol groups was slightly,
but not significantly, higher than in the wheat flour group. The
incidence of caries was lowest in the xylitol group.
In a twofold experiment using caries-active rats, Grenby and
Phillips (Ref. 77) evaluated: (1) The cariogenicity of lactitol,
sucrose, and xylitol at a level of 160 g per (/) kilogram (kg), a level
stated to approximate the average sucrose content of the diet in
developed countries, and (2) the cariogenicity of lactitol in a sweet
biscuit compared to a sucrose-sweetened biscuit. In the first
experiment, the sweetener was incorporated into a laboratory chow
containing white flour, skim milk powder, liver powder, and a vitamin-
mineral supplement. In the second part of the experiment, biscuits,
containing 166 g of lactitol/kg, were incorporated into the animal chow
for a final concentration of lactitol of 110 g/kg. Animals were fed the
diets for a period of 8 wk. Experiment 1 showed highly significant
differences in caries score, total number of lesions, and severity of
lesions in the sugar alcohol groups compared to the sucrose controls.
The sugar alcohol groups had very few caries, and differences between
groups were not significant. The animals in both the xylitol and
lactitol groups required several weeks to adapt to the diets, showing
increased water intake and decreased food intake. Because of poor
physical condition, only 11 of the 22 rats in the xylitol group
completed the full 8-wk test. Animals on the sucrose diet were
significantly heavier than the sugar alcohol animals.
Results of the second test showed highly significant differences
between the lactitol- and sucrose-biscuits groups in all caries
parameters. The average caries score for the lactitol group was less
than one per animal. Weight gains, however, were consistently lower,
and water intake increased in the lactitol group.
The results of the above animal studies show that animals fed sugar
alcohols in animal chow had fewer and less extensive caries than
animals fed sucrose. The studies also show that, in general, rats do
not eat as much of a sugar alcohol-containing diet as a sucrose-
containing diet and, therefore, tend to gain less weight and have more
physiological problems.
E. Summary of Human and Animal Studies
1. Xylitol
In its 1978 review of the studies on xylitol, FASEB concluded that
xylitol appeared to be noncariogenic in studies evaluating the effect
of sucrose
[[Page 37520]]
replacement with xylitol and in studies evaluating the effect of
partial replacement of sucrose with xylitol in chewing gum (Ref. 14).
However, FASEB concluded that it was essential that these studies be
replicated by other workers in order to confirm the observations and
conclusions.
Rekola (Refs. 23 and 25) conducted a followup assessment of results
from the 2-yr Turku sugar study evaluating the progression of incipient
carious lesions and lesion sizes on buccal smooth surfaces with dietary
substitution of xylitol for sucrose. In the 2-yr Turku sugar study,
dietary xylitol was almost completely substituted for sucrose. Subjects
were assigned to groups based on individual preference. Rekola examined
color dental photographs, taken during the 2-yr study, of 33 subjects
in the sucrose group and 47 subjects in the xylitol group. The xylitol
group showed significantly smaller white spot lesions and had a
significantly lower caries score compared to the sucrose group.
Results of several more recent human caries studies (Refs. 22, 26,
and 28 through 30) reported significantly fewer caries in the xylitol
group compared to the sucrose group. Kandelman and Gagnon (Ref. 22)
reported significantly less NPD and incidence of DMFT in school
children chewing three sticks per day of xylitol gum (3.4 g) or xylitol
and sorbitol gum (0.9 g xylitol and 2.4 g sorbitol) compared to the
nongum control group. Results of xylitol field studies in Hungary
(Refs. 26 and 28), French Polynesia (Refs. 29 and 30), and Thailand
(Ref. 29) conducted by WHO showed lower caries incidence and caries
increment rate in children consuming xylitol and sorbitol in chewing
gum (Ref. 29) and xylitol in other snack foods (Ref. 30) compared to a
nonsugar alcohol group. However, results of the gum study in French
Polynesia and Thailand (Ref. 29) were confounded by the presence of
fluoride in the gums tested. In addition, the prevalence and incidence
of dental caries in these population groups were high and increasing
and do not reflect the general healthy population of the United States.
The effect of xylitol on acid production or plaque pH was studied
in ten studies (Refs. 38, 39, 41, 43 through 46, 48, 50, and 76). In
nine of these (Refs. 38, 39, 41, 43 through 46, 48, and 50), xylitol
was found to result in negligible to no acid production with little to
no change in plaque pH. Similarly, results showed no significant effect
of xylitol on resting plaque pH. Plaque pH from exposure to xylitol was
always significantly higher than that of sucrose or glucose.
Twelve animal studies (Refs. 52, 54, 56 through 60, 62, 63, 68, 73,
and 77) evaluated the effects of xylitol on dental caries in rats or
hamsters. Eight of these (Refs. 52, 57 through 60, 62, 63, and 77) used
a test diet that contained only one sweetener, either sucrose or
xylitol. In all of these studies, there were significantly fewer caries
reported in animals consuming the basal diet with xylitol compared to
sucrose controls. The incidence of caries was also significantly less
in the xylitol group compared to animals consuming isomalt (Ref. 63)
and sorbitol (Ref. 52). The concentrations of xylitol in the test diets
ranged from 10 percent up to 30 percent by weight.
Results of the animal studies evaluating the effect of xylitol in
diets containing sucrose (Refs. 54, 56, 68, and 73) showed mixed
results depending on the concentrations of sucrose and xylitol in the
test diets. Havenaar et al. (Ref 54) showed no significant difference
in caries in animals consuming a diet with sucrose and 5-percent
xylitol, but a significant difference in caries when the sucrose was
lowered to 20-percent of the diet and xylitol 5-percent. Grenby and
Colley (Ref. 56) reported a high caries level in animals consuming
either a diet containing 46-percent sucrose or 36-percent sucrose and
10-percent xylitol. The caries score was significantly lower in rats
consuming a diet with 26-percent sucrose and 20-percent xylitol
compared to the 46-percent sucrose diet. An in vitro microbiological
test showed no acid production by S. mutans from xylitol. Van der
Hoeven (Ref. 73) reported significantly fewer caries in rats consuming
a diet with 25-percent xylitol compared to the rats consuming a basic
diet with 25-percent sucrose. The xylitol group also had fewer caries
than the wheat flour control group.
2. Sorbitol
In its March 1979, review of sorbitol in health and disease (Ref.
15), FASEB reviewed available animal and human studies regarding the
cariogenicity of sorbitol. FASEB concluded that the weight of evidence
from animal studies suggests that sorbitol is less cariogenic than
sucrose, fructose, glucose, and dextrin. Based on the human studies
published in the early to mid-1970's, FASEB noted that the results do
not provide definitive data on the effect of sorbitol on the caries
process. It noted that the results of studies on plaque pH suggest that
sorbitol is slowly fermented to plaque pH levels of about 6. It also
said that some studies have provided evidence of adaptation of oral
flora after long-term use of sorbitol-containing products. FASEB noted
that a human population that regularly consumes sorbitol-containing
foods, such as jams and jellies, baked goods, or other food products,
has not been identified and studied to establish whether sorbitol
significantly alters the carious process.
Two studies submitted with the petition evaluated the cariogenicity
of sorbitol in chewing gum (Refs. 20 and 32), and one study (Ref. 35)
evaluated the effect of sorbitol in chewing gum on demineralization of
enamel. Moller and Poulsen (Ref. 20) reported an increased number of
sound tooth surfaces and a smaller caries increment rate in children
consuming sorbitol gum containing calcium phosphate compared to the
control group that did not consume chewing gum. However, the presence
of calcium phosphate, which acts as a buffer in saliva to help reduce
its acidity, and the absence of gum chewing in the control group,
confound these observations.
Glass (Ref. 32) reported no significant differences in the number
of DF surfaces or teeth in children using sorbitol chewing gum for 2 yr
compared to a no-gum group. This study, however, did not consider the
effect of chewing gum per se on dental caries.
Leach et al. (Ref. 35) conducted an intraoral test in subjects
fitted with bands containing human enamel with artificial white spot
lesions. The subjects consumed sucrose-containing snacks. During one of
the test periods, the subjects chewed gum containing sorbitol with
small amounts of mannitol, HGS, and aspartame, for 20 min at a time
after each meal and snack. The study showed significantly more
remineralization during the sorbitol gum period compared to baseline
and the no-gum (sucrose) period. Results of this study are confounded,
however, because of the duration (i.e., 20 min) and timing (i.e.,
immediately after meals and snacks) of the gum chewing. In addition,
the effect of sorbitol alone cannot be determined because of the
presence of other sugar alcohols and aspartame in the test gum.
Banoczy et al. (Ref. 21) reported a significantly lower caries
increment in children consuming sorbitol-containing sweets between
meals compared to children consuming sucrose-containing sweets between
meals over a 2-yr period. Differences between groups were not
significant during the third yr of this study, however, the authors
attributed the lack of significance during the third yr to the trading
of sweets between groups.
[[Page 37521]]
Twelve studies evaluated changes in plaque pH after exposure to
sorbitol-sweetened mouth rinses (Refs. 39 through 41, 45, and 47),
solutions (Refs. 38, 46, and 76), tablets (Ref. 42), mints (Ref. 49),
chewing gum (Ref. 50), and licorice (Ref. 43). Plaque pH changes in the
presence of sorbitol decreased from baseline pH but remained
approximately at or above a pH of 6.0 (Refs. 39 through 42, 45 through
47, and 50). Bibby and Fu (Ref. 38) reported progressively decreasing
plaque pH values in vitro with increasing concentrations of sorbitol in
a concentrated plaque suspension. Only slight decreases in pH were
reported in 0.1- to 1.0-percent solutions. In the presence of a 10-
percent sorbitol solution, plaque pH dropped to about 5.8. Grenby et
al. (Ref. 76) reported a pH of about 6.0 after 12 h and a final pH in
vitro of about 4.6 after 24 h of incubating concentrated plaque with
10-percent sorbitol. The results of these studies suggest that higher
concentrations of sorbitol may lead to further decreases in plaque pH
to a level that may become detrimental to tooth enamel (i.e., at or
below pH 5.5).
Park et al. (Ref. 49) found that use of sorbitol mints or mints
with a blend of sorbitol and xylitol helped reduce the acidogenic
potential of certain snack foods, although final pH values remained
low. Toors and Herczog (Ref. 43) showed that plaque pH is affected by
more than the sweetener component of a food. Results of plaque pH in
vivo with an experimental licorice, containing sorbitol, soy flour, and
potato starch derivative among other ingredients, showed a minimum pH
of about 5.5. A sucrose-containing licorice used in this study lowered
plaque pH to about 5.0. The fermentability of both the potato starch
derivative (82 percent) and soy flour (75 percent) contributed to the
observed changes in plaque pH in the experimental licorice. The
fermentability of sorbitol in the experimental licorice was 12 percent.
Five studies (Refs. 39 through 41, 43, and 48) measured the APA of
plaque with sorbitol. In all cases, sorbitol was fermented slowly with
a reported range of acid production of 10 to 30 percent compared to
sucrose or glucose. The higher acid production rate (i.e., 30 percent)
was attributed to adaptation to sorbitol by S. mutans and other plaque
microorganisms capable of fermenting carbohydrates. Havenaar et al.
(Ref. 46) also reported a marked increase in fermentation of sorbitol
and other sugar alcohols after multiple subculturing of plaque
microorganisms with the sugar alcohol. However, the investigators
reported that adaptation to sorbitol and other sugar alcohols was lost
after subculturing once in glucose.
Results of animal studies evaluating sorbitol (Refs. 35, 52, 58,
59, 62, 64, and 73) showed significantly fewer caries in the sorbitol
group than in the sucrose group. However, use of sorbitol resulted in
more caries compared to animals consuming other sugar alcohols, such as
xylitol and HSH (Refs. 52, 64, and 73). The concentration of sorbitol
in these studies ranged from 10 percent up to 56 percent.
3. Mannitol
In its August 1979, review of mannitol in health and disease, FASEB
(Ref. 16) reviewed available animal and human studies regarding the
effect of mannitol on acid production, plaque pH changes, and changes
in microhardness of bovine enamel in an ICT. It noted that human plaque
studies in vivo or in vitro found that plaque pH decreases from 0 up to
1.0 units over a 30-min test period. FASEB concluded that the results
were consistent with the results of animal experiments showing that
mannitol, in the absence of adaptation of the oral microflora, is less
cariogenic than sucrose.
Bibby and Fu (Ref. 38) measured in vitro plaque pH changes, over a
20-min incubation period, in the presence of increasing concentrations
of mannitol (0.1-, 1.0-, and 10-percent concentrations) in a
concentrated plaque suspension. Results showed that plaque pH decreased
with increasing concentrations of mannitol. Final plaque pH values were
5.67, 5.54, and 5.22, respectively. Similar plaque pH values were
reported by Grenby et. al. (Ref. 76). Results of the Grenby study
showed that a 1-percent solution of mannitol, when incubated for 24 h
with concentrated plaque and pieces of a human molar tooth, resulted in
slight acid production and pH decrease over a 12-h period, but that
after 24 h, the final pH was about 5.1. However, results from an in
vitro demineralization test showed very little loss of calcium and
phosphorus, significantly less than the loss of minerals with glucose.
Results of other studies, however, show that mannitol results in
little change to plaque pH. Birkhed and Edwardsson (Ref. 39) reported
only slight changes in plaque pH following use of a mouth rinse with a
concentrated solution of mannitol. In addition, they reported an acid
production rate from mannitol in dental plaque suspension of 0 percent
compared to sucrose (100 percent). Gehring and Hufnagel (Ref. 45) used
intraoral measurements to evaluate the effect of sugar alcohols on
plaque pH. Results of plaque exposed to a 20-percent mannitol solution
showed the minimum pH obtained was slightly above 6.0. The plaque
samples in these two studies were not concentrated as they were in the
study by Bibby and Fu (Ref. 38) or by Grenby et al. (Ref. 76), which
may account for the differences in plaque pH values reported for
mannitol solutions. The results of one other in vitro microbiological
study, with 10-percent mannitol and an incubation time of 48 h (Ref.
62), support the observation that mannitol is fermented very slowly,
resulting in little acid production and small pH changes.
Animals fed mannitol (Refs. 59 and 64) or maltitol (Refs. 66, 67,
and 69) showed significantly fewer caries compared to animals fed
sucrose diets. The concentrations of the sugar alcohols in these
studies ranged from 10 to 56 percent. An in vitro microbiological study
(Ref. 62) showed that a 10-percent solution of mannitol was fermented
very slowly.
4. Maltitol
Three studies (Refs. 33, 34, and 36) measured the effects on enamel
decalcification of maltitol and sucrose solutions using an ICT with
bovine enamel fragments adhered to a partial denture. Ikeda and
coworkers (Ref. 33) showed significantly more decalcification in the
presence of sucrose as compared to maltitol. Additional rat caries
tests were in agreement with the results of the ICT. Rats fed a diet
with maltitol had significantly fewer caries than the sucrose group. In
this study maltitol was almost noncariogenic. Yagi (Ref. 34) reported
significantly harder enamel after exposure to maltitol than after
exposure to sucrose. Lack of details in this study, however, make it
difficult to completely interpret the results. Rundegren (Ref. 36)
reported significantly less enamel demineralization with maltitol
compared to sucrose. The authors associated the changes that they
observed in enamel hardness in the maltitol group with the effects of
other dietary carbohydrates and not maltitol. Sucrose was found to
exert an effect on enamel hardness that is not related to the effects
of other dietary carbohydrates.
Three studies (Refs. 39, 41, and 46) evaluated plaque pH or acid
production in maltitol. Birkhed and Edwardsson (Ref. 39) measured in
vitro acid production and pH changes in human dental plaque following
the use of various sweeteners in a mouth rinse. The results with
maltitol showed an acid production rate of 10 to 30 percent
[[Page 37522]]
of that of sucrose. Changes in plaque pH in the presence of maltitol
showed only a slight decrease from baseline pH (about pH 6.9).
Birkhed et al. (Ref. 41) measured in vivo pH changes in human
dental plaque after subjects consumed lozenges sweetened with various
sweeteners for 3 mo and then rinsed with a mouth rinse sweetened with
the same sweetener as in the lozenge. A sucrose mouth rinse was also
used by each sweetener group. Results with maltitol showed small, but
some significant, changes in plaque pH compared to baseline pH (about
pH 7.0) over the 30-min test period. The lowest plaque pH recorded,
however, was about pH 6.8. In vitro acid production with maltitol was
found to be about 26 to 32 percent of glucose.
Havenaar et al. (Ref. 46) measured changes in pH and acid
production in vitro in growing cultures of oral bacteria obtained from
caries active and caries free subjects. Results showed that a 1 percent
solution of maltitol was slowly fermented to acid by plaque bacteria.
Cell suspensions of S. mutans in maltitol showed pH decreased from a
baseline of about pH 7.0 to about pH 6.5. Adaptation of S. mutans by
frequent subculturing in maltitol showed a marked increase in
fermentation by S. mutans. However, the ability to ferment the sugar
alcohol was lost after one subculturing of the adapted strain in
glucose.
5. Lactitol
Havenaar et al. (Ref. 46) showed that a 1 percent solution of
lactitol was fermented by S. mutans and Actinomyces. Cell suspensions
of S. mutans in lactitol showed pH decreased from a baseline of about
pH 7.0 to about pH 6.5 or above after a 2-h incubation period.
Adaptation of S. mutans by frequent subculturing in lactitol showed a
marked increase in fermentation by S. mutans to give a plaque pH of
about 5.0. However, the ability to ferment the sugar alcohol was lost
after one subculturing of the adapted strain in glucose. Grenby et al.
(Ref. 76) showed that a 1-percent solution of lactitol, when incubated
for 24 h with human plaque and pieces of a human molar tooth, resulted
in slight acid production and a final pH of about 6.3 and almost no
loss of calcium and phosphorus from tooth enamel.
Results of two animal studies (Refs. 73 and 77) showed that
substitution of lactitol for sucrose in laboratory chow resulted in
significantly fewer caries in the lactitol group compared to the
sucrose group. The lactitol group (Ref. 73) experienced slightly, but
not significantly, more caries than the xylitol group and the wheat
flour control group and fewer caries than the sorbitol group. There was
no significant difference between the caries score in animals fed
lactitol-containing or xylitol-containing chow (Ref. 77). There were
significantly fewer caries in animals fed lactitol-containing biscuits
compared to the sucrose biscuit group (Ref. 77). The average caries
score in the lactitol biscuit group was less than one per animal.
6. Isomalt
Two studies investigated the effects on plaque pH with isomalt
(Refs. 38 and 45). Bibby and Fu (Ref. 38) measured pH changes in fresh
plaque from adult volunteers with increasing concentrations of isomalt.
Results showed that as the concentration of the sugar alcohol
increased, the pH of the plaque decreased. The range of plaque pH
values reported for isomalt was from 6.6 (0.1 percent solution) to
approximately 5.7 (10-percent solution). Gehring and Hufnagel (Ref. 45)
reported a minimum plaque pH of about 6.0 after 5 min with isomalt.
This value increased gradually over the next 27 min to about pH 6.3. As
discussed above, the methods and type of dental plaque must be
considered when comparing the results of these studies.
Results of animal studies with concentrations of isomalt from 16 to
30 percent of the rat diet showed significantly fewer caries compared
to sucrose diets (Refs. 57, 60, 62, 63, 65, and 70). The caries
incidence was high in xerostomized rats consuming either sucrose or
isomalt (Ref. 57). The isomalt group of nonxerostomized rats, however,
had significantly fewer caries than the sucrose group.
7. HGS and HSH
Frostell et al. (Ref. 31) studied the effect on caries increment in
children of substitution of HSH for sucrose in candy. The results of
this study are confounded for a number of reasons (see Table 2) and do
not support a significant dental benefit from the use of HSH candies in
place of sucrose-containing candies.
Rundegren et al. (Ref. 36) measured enamel hardness in the presence
of sucrose, sodium chloride, or HSH using an ICT. The investigators
reported significantly less enamel demineralization with HSH. The
results of the study were that only sucrose promoted demineralization
over and above the effect of dietary carbohydrates. The authors
attributed the demineralization measured in the presence of HSH to the
effect of dietary carbohydrates.
Eight studies measured plaque pH changes from exposure to HSH in
solutions (Refs. 38 and 46), rinses (Refs. 39, 41, 45, and 47), and
candy (Refs. 42 and 43). Bibby and Fu (Ref. 38) showed that as the
concentration of HSH increased, plaque pH decreased. The lowest plaque
pH value (10-percent solution of HSH) obtained was about 5.0. Havenaar
et al. (Ref. 46) showed that a 1-percent solution of HSH was fermented
by S. mutans and Actinomyces. Cell suspensions of S. mutans in HSH
showed a pH decrease from a baseline of about pH 7.0 to about pH 6.5.
Adaptation of S. mutans by frequent subculturing in HSH showed a marked
increase in fermentation by S. mutans to give a plaque pH of slightly
below 6.0. However, the ability to ferment the sugar alcohol was lost
after one subculturing of the adapted strain in glucose.
Birkhed and Edwardsson (Ref. 39) measured plaque pH in vitro
following the use of a mouth rinse containing Swedish or French HSH.
French HSH appeared to have little effect on plaque pH. Plaque pH
values remained slightly below or at 7.0. Swedish HSH showed a decrease
in plaque pH within 5 to 10 min to just less than pH 6.0. Over the
remaining 20 min, the pH increased to just over 6.0. Birkhed et al.
(Ref. 41) measured pH changes in human dental plaque after subjects
consumed lozenges sweetened with Swedish HSH for 3 mo and then rinsed
with a mouth rinse sweetened with Swedish HSH. Plaque pH was also
measured after a sucrose mouth rinse. The results of the study showed
that HSH resulted in a drop in plaque pH in all tests; however, the
minimum pH values reached were above 6.0. Gehring and Hufnagel (Ref.
45) reported an intraoral plaque pH change with a HSH rinse (20 percent
solution) from about pH 6.6 to about 5.6.
Jensen (Ref. 47) showed interproximal plaque pH values from five
different HGS rinses were statistically significantly different
compared to the sucrose control. Differences between the HGS test
solutions and a sorbitol control were not significantly different. The
minimum pH values obtained with the HGS solutions were above pH 6.0.
Composition of the HGS test substances was not provided.
Frostell (Ref. 42) reported a slight decrease in vitro plaque pH
(from about 6.7 to about 6.5) after subjects consumed HSH candy. After
consuming a sucrose lozenge, plaque pH decreased to about 5.8. A
sucrose solution resulted in a minimum plaque pH of about 5.3. Toors
and Herczog (Ref. 43) showed that plaque pH is affected by more than
the sweetener component of a food. Results
[[Page 37523]]
of plaque pH in vivo with an experimental licorice, containing soy
flour, HPS, and potato starch derivative among other ingredients,
showed a minimum pH of about 5.5. The fermentability of the HPS (60
percent), potato starch derivative (82 percent) and soy flour (75
percent) contributed to the observed changes in plaque pH in the
experimental licorice.
Acid production in vitro was reported in two studies (Refs. 39 and
51). Birkhed and Edwardsson (Ref. 39) reported an acid production rate
from French HSH of 20 to 40 percent and from Swedish HSH of 50 to 70
percent compared to glucose syrups. Birkhed and Skude (Ref. 51)
reported significantly lower acid production rates (i.e., slower rate
of fermentation) from a 3 percent solution of Swedish HSH (61.5
percent) compared to glucose (99.7 percent). The investigators also
reported that HSH was metabolized significantly more slowly than
soluble starch.
Results of animal studies evaluating the effect of HSH showed the
sweetener to be relatively noncariogenic compared to sucrose (Refs. 52,
53, 64, and 69). Differences in the incidence of caries between the
sucrose and HSH groups were significant.
IV. Decision To Propose a Health Claim Relating Sugar Alcohols To the
Nonpromotion of Dental Caries
FDA limited its review of the scientific evidence relating sugar
alcohols and dental caries to those studies evaluating changes in
plaque pH, plaque acid production, decalcification or remineralization
of tooth enamel, and the incidence of dental caries with sugar
alcohols. FDA considered these limitations to be appropriate because
previous Federal government and other authoritative reviews had focused
on these areas (Refs. 14 through 16), and the majority of research
efforts to date have focused on these areas.
FDA tentatively concludes that, based on the totality of publicly
available scientific evidence regarding the relationship among sugar
alcohols, plaque pH, and dental caries, there is significant scientific
agreement to support the relationship between the use of xylitol,
sorbitol, mannitol, maltitol, isomalt, lactitol, HSH, HGS, or a
combination of these sugar alcohols and the nonpromotion of dental
caries. Thus, it appears that use of a health claim relating the use of
sugar-alcohol containing products to dental caries will be useful in
helping consumers identify food products consumption of which will not
promote the development of dental caries.
A. Xylitol
In its 1978 review of the xylitol studies, FASEB concluded that
xylitol appeared to be noncariogenic in studies evaluating the effect
of sucrose replacement with xylitol and in studies evaluating the
effect of partial replacement of sucrose with xylitol in chewing gum
(Ref. 14).
The agency reviewed over 15 studies published since the FASEB
report that evaluated the relationship between xylitol and dental
caries, plaque pH, and acid production. Overall results from the human
caries field trials (Refs. 26 and 28) suggest that substitution of
xylitol-containing foods and chewing gums for sucrose-containing foods
and chewing gums is associated with a lower incidence of dental caries.
Plaque pH and acid production studies further support this result. In
both in vivo and in vitro studies, xylitol had negligible to no effect
on plaque pH or plaque acid production. In some instances, xylitol
increased plaque pH above the mean baseline value, suggesting that
xylitol may truly be nonpromotional of dental caries. The results of
over 10 animal studies confirm the observations from clinical and in
vitro studies. Substituting xylitol (from 10 to 30 percent) for sucrose
in a basic laboratory chow resulted in significantly fewer dental
caries. FDA tentatively concludes that the overall results from human
and animal studies strongly support the observation that xylitol does
not promote acid production in plaque and, therefore, does not promote
dental caries.
B. Sorbitol
In its 1979 report on sorbitol, FASEB concluded that the weight of
evidence from animal studies suggests that sorbitol is less cariogenic
than sucrose and other fermentable sugars (Ref. 15). The report noted
that the results of human plaque studies show that sorbitol does not
lower plaque pH below 5.5, the pH of plaque where decalcification may
begin. FASEB concluded that it could be assumed that sorbitol may have
similar relative cariogenic properties in humans as observed in
animals.
The agency reviewed over 10 clinical studies with sorbitol
published since the FASEB report. Subjects consuming sorbitol-
containing sweets between meals experienced fewer dental caries than
those consuming sucrose-containing sweets. Plaque pH and acid
production studies consistently show that sorbitol is slowly fermented
by plaque microflora and by S. mutans in particular. However, results
show that plaque acid did not decrease pH to levels associated with
incipient enamel decalcification (i.e., approximately at pH 5.5 or
below). There is some evidence that suggests that long-term,
uninterrupted use of sorbitol results in adaptation by S. mutans and
other plaque microorganisms and, therefore, in more acid production.
However, there are no human caries trials to show whether such
adaptation results in a change in the incidence of dental caries. There
is some evidence to show that adaptation may be lost in the presence of
other sugars.
The results of six animal studies confirmed the observations from
human studies. The incidence of caries in animals consuming diets
containing sorbitol was significantly less than the caries incidence in
animals consuming diets containing sucrose. FDA tentatively concludes
that the overall results from human and animal studies show that oral
bacteria cannot be sustained in the presence of sorbitol, and that
changes in acidity are within a range that is safe for tooth enamel.
C. Mannitol
In its 1979 report on mannitol, FASEB concluded that results of
acid production, plaque pH changes, and changes in microhardness of
bovine enamel were consistent with the results of animal experiments
indicating that mannitol, in the absence of adaptation of the oral
microflora, is less cariogenic than sucrose (Ref. 16). One study
evaluated plaque pH with mannitol in a concentrated plaque suspension
in vitro (Ref. 38). One and ten percent solutions of mannitol resulted
in a plaque pH of 5.5 or below. Contrary to these results, however,
three studies showed only slight acid production and small changes in
plaque pH to a value not below pH 6.0 from mannitol (Refs. 39, 45, and
76). Likewise, there was little evidence of demineralization from
mannitol in vitro (Ref. 76). Two rat studies, in which mannitol was
substituted for sucrose in animal chow, showed significantly fewer
caries with the mannitol diet (Refs. 59 and 64). FDA tentatively
concludes that the overall results from both human and animal studies
support the claim that mannitol does not promote dental caries.
D. Maltitol
Results of three ICT's showed significantly less decalcification
with maltitol than sucrose. Additional plaque pH studies showed that
maltitol is fermented very slowly (acid production of 10 to 30 percent)
compared to sucrose and is associated with small plaque pH changes from
resting baseline values.
[[Page 37524]]
Four animal studies confirmed that maltitol was significantly less
cariogenic than sucrose. FDA tentatively concludes that the overall
results from both human and animal studies support the claim that
maltitol does not promote dental caries.
E. Isomalt
The agency reviewed two plaque pH studies evaluating the acidogenic
potential of isomalt. Results with 10 percent isomalt showed a minimum
in vitro plaque pH of 5.7. An intraoral test with a 20 percent solution
of isomalt reported a minimum pH of about 6.0. Results of five animal
studies consistently showed that isomalt was significantly less
cariogenic than sucrose. FDA tentatively concludes that the overall
results show that isomalt does not lower plaque pH below 5.5 and does
not promote dental caries.
F. Lactitol
Two in vitro plaque pH studies showed that lactitol produced little
acid and only slight changes in plaque pH from resting baseline values.
Results of two animal studies are consistent with these results and
showed lactitol to be significantly less cariogenic than sucrose. The
cariogenicity of lactitol was not significantly different than xylitol.
FDA tentatively concludes that the overall results support the claim
that lactitol does not promote dental caries.
G. Hydrogenated Starch Hydrolysates and Hydrogenated Glucose Syrups
In an ICT, a solution of HSH resulted in significantly less
demineralization than sucrose. The investigators attributed the
observed demineralization with HSH to an effect of other dietary
components. The effects of sucrose on enamel demineralization, however,
were noted to be over and above the effect of other dietary components.
Seven studies evaluating the effect of HSH on plaque pH showed
inconsistent results in final pH values reported. The differences in
results are attributed to the source of the HSH. HSH is manufactured by
hydrolyzing a source of food grade starch (usually potato or corn
starch) with acid or an enzyme to a mixture of sugars and dextrins of
various glucose lengths (i.e., glucose syrups). The hydrogenated
mixture contains sorbitol, maltitol, maltitriol, maltotrititol, and
hydrogenated dextrins of various molecular weights (Ref. 79). The
percentage of each component sugar alcohol in the final substance
depends on the manufacturing process and controls. The two major forms
of HSH (i.e., one manufactured in Sweden and the other in France) used
in the studies reviewed gave dramatically different results in plaque
pH and acid production tests. The Swedish version, which has a higher
percentage of higher molecular weight, fermentable polysaccharides than
the French version, produced plaque pH values of 5.5 to 6.0 and an acid
production of 50 to 70 percent compared to sucrose. The French version
produced final plaque pH values above 6.0 and an acid production rate
of 20 to 40 percent of sucrose. Results with HGS of unidentified
composition showed minimum plaque pH values all above 6.0. Results of 4
rat studies support the observations that HSH (source not identified)
is significantly less cariogenic than sucrose. FDA tentatively
concludes that the overall results support the claim that HSH and HGS
do not promote dental caries.
Based on its review of the scientific evidence, the agency noted
that the HSH and HGS sugar alcohol mixtures may vary in their
acidogenic response in dental plaque. For example, HSH manufactured in
Sweden usually gave a lower plaque pH response than the French version
of HSH. This variation in acidogenic response has been attributed to
the differences in the chemical composition of these substances. HSH
and HGS are not well defined chemical substances as are xylitol and
sorbitol. Instead, the sugar alcohol compositions of these substances
will vary depending on the manufacturing process. Therefore, the agency
is asking for comments on how to determine whether sugar alcohol
mixtures, such as HSH, when used in a food whose label bears a dental
caries health claim, are in compliance with any final rule resulting
from this proposal.
V. Decision To Propose An Exemption From Sec. 101.14(E)(6) For Chewing
Gum and Confectioneries
Section 101.14(e)(6) provides, as stated above, that except for
dietary supplements or where provided for in other regulations in part
101, subpart E, to be eligible to bear a health claim, a food must
contain 10 percent or more of the reference daily intake or the daily
reference value for vitamin A, vitamin C, iron, calcium, protein, or
fiber per reference amount customarily consumed before there is any
nutrient addition.
The petition states that products containing sugar alcohols often
will not be able to satisfy the requirement of Sec. 101.14(e)(6)
because the products utilizing sugar alcohols are largely chewing gum
and confectioneries, none of which are a significant source of any
nutrients. The petition states that the use of these products in lieu
of traditional sugar-based confectionery would be consistent with
public health recommendations, and that the health claim statement,
``useful only in not promoting tooth decay,'' is an important and
useful message for consumers in making decisions on which foods to
purchase.
FDA has tentatively determined that there is significant public
health evidence to support providing an exemption to Sec. 101.14(e)(6)
for sugar alcohol-containing foods, e.g., chewing gums, hard candies,
and mints. In the Surgeon General's Report (Ref. 7), dental caries is
recognized as an important and widespread public health problem in the
United States. Although dental caries among children are declining, the
overall prevalence of the condition imposes a substantial economic
burden on American health care costs. The Surgeon General's report
states that of the 13 leading health problems in the United States,
dental disorders rank second in direct costs (Ref. 7).
The role of sugars, and of sucrose in particular, in the etiology
of dental caries is well established. Caries-producing bacteria can
readily metabolize a range of simple sugars (e.g., sucrose, glucose,
fructose) to acids that can demineralize teeth. The unique role of
sucrose, however, is related to its ability to be used by S. mutans,
the primary etiologic agent in coronal caries, and other oral bacteria
to form extracellular polymers of glucose or fructose that adhere
firmly to tooth surfaces (Ref. 7).
The Surgeon General's report recommends several types of
intervention to help reduce the risk of dental caries. The diet-related
factors include the use of fluoridated drinking water and control of
sugars consumption. In this regard, the Surgeon General's report
recommends that those who are particularly vulnerable to dental caries,
especially children, should limit their consumption and frequency of
use of foods containing relatively high levels of sugars.
FDA agrees that limiting the amount of sugars in the diet is one
important approach to help reduce the risk of dental caries. Sugar
alcohols can be used to replace dietary sugars in food by providing
sweetness and usefulness as bulking agents. Sugar alcohol-containing
chewing gum and confectioneries, such as hard candies and mints, are
specifically formulated without dietary sugars. Although these foods
have little or no nutritional value,
[[Page 37525]]
they are an important alternative to sucrose-containing snacks.
Therefore, FDA tentatively finds that the use of health claims on the
label of sugar alcohol-containing products will facilitate compliance
with dietary guidelines that recommend a reduced intake of dietary
sugars to reduce the risk of dental caries. Moreover, the sugar alcohol
and dental caries health claim, if authorized, will apply in large
measure, although not entirely, to snack foods that do not play a
fundamental role in structuring a healthy diet.
Section 101.14(e)(6) was included in FDA's regulations to ensure
that those foods that bear a health claim are useful in structuring a
healthy diet. Usually usefulness in structuring a healthy diet derives
from the vitamin, mineral, protein, or fiber content of the food. In
this case, however, FDA tentatively finds that the replacement of
dietary sugars with sugar alcohols will help reduce the risk of dental
caries and thus will help to facilitate compliance with the dietary
guidelines. In recognition of the special character of the foods
involved, FDA tentatively concludes that it is appropriate to exempt
these food products from Sec. 101.14(e)(6). Therefore, in new
Sec. 101.80(c)(1), FDA is proposing to exempt sugar alcohol-containing
food products from the provisions of paragraph 101.14(e)(6).
VI. Description And Rationale For Components Of Health Claim
A. Relationship Between Sugar Alcohols and Dental Caries
In proposed Sec. 101.80(a), FDA describes the relationship between
sugar alcohols and dental caries. Dental caries is a multifactorial
disease, characterized by the demineralization of the surface of tooth
enamel by acid-forming organisms in dental plaque. It is well
established that the relationship between sugars consumption and dental
caries is one of cause and effect within the multifactorial context
(Refs. 71 and 72). The role of sucrose in the etiology of dental caries
is related to its ability to be metabolized by oral bacteria into
extracellular polymers that adhere firmly to the tooth surfaces, at the
same time forming acids that can demineralize tooth enamel (Ref. 7).
The extracellular polymers that adhere to tooth surfaces (i.e., plaque)
facilitate the further attachment of additional plaque to teeth and the
proliferation of bacteria. Although saliva can help neutralize plaque
acids and influence the attachment of oral bacteria to the tooth
surface (Ref. 7), it has limited access to the acids generated at the
tooth surface beneath the plaque.
Diets in the United States tend to be high in sugars. Although
there has been a decline in the prevalence of dental caries in the
United States, there has been no decline in the consumption of sugars.
Furthermore, the incidence of dental caries is still widespread (Ref.
7).
Sugar alcohols are used as sweeteners and bulking agents to replace
dietary sugars in foods. Because of their composition, sugar alcohols
are not as fermentable by plaque bacteria as sucrose and are,
therefore, less cariogenic than dietary sugars. Replacing dietary
sugars with sugar alcohols helps to maintain dental health.
B. Significance of Sugar Alcohols in the Caries Process
As explained in section IV of this document, based on the totality
of the publicly available evidence, FDA has tentatively concluded that
there is significant scientific agreement among experts qualified by
training and experience to evaluate such claims that there is adequate
scientific evidence to conclude that the sugar alcohols xylitol,
sorbitol, mannitol, maltitol, isomalt, lactitol, HSH, and HGS are less
cariogenic than sucrose and do not promote dental caries. In proposed
Sec. 101.80(b), FDA discusses the significance of the relationship
between sugar alcohols and dental caries.
Sugar alcohols have been shown in human and animal studies to be
nonfermentable (i.e., xylitol) or slowly fermentable (i.e., sorbitol,
maltitol, mannitol, isomalt, lactitol, HSH, and HGS) by S. mutans and
other acid-forming microorganisms in dental plaque. Human studies have
shown a reduced rate of acid production in plaque and, in some studies,
a reduced incidence of dental caries from the use of sugar alcohol-
containing products.
C. Nature of the Claim
In new Sec. 101.80(c)(1), FDA is proposing that all requirements of
Sec. 101.14 be met except, as explained above, that sugar alcohol-
containing foods are exempt from Sec. 101.14(e)(6).
Under Sec. 101.14(d)(3), nutrition labeling in accordance with
Sec. 101.9 must be provided on the label or labeling of any food for
which a health claim is made. Therefore, if FDA adopts this proposed
regulation, the labeling of the amount of sugar alcohol in a serving
will have to be declared on the nutrition label in accordance with
Sec. 101.9(c)(6)(iii) when a claim is made on the label or in labeling
about sugar alcohols and dental caries.
In new Sec. 101.80(c)(2)(i), FDA is proposing to authorize a health
claim on the relationship between sugar alcohols and the nonpromotion
of dental caries. This action is consistent with the agency's review of
the scientific evidence, which showed that, although sugar alcohols are
slowly fermented by S. mutans and can form some acid, they do not
contribute to the promotion of dental caries.
In new Sec. 101.80(c)(2)(i)(A), the agency is proposing to require
that in describing the relationship between sugar alcohols and dental
caries, the claim states ``does not promote,'' ``useful in not
promoting,'' or ``expressly for not promoting'' dental caries. FDA
finds that these terms accurately describe the relationship between
sugar alcohol consumption and dental caries.
In new Sec. 101.80(c)(2)(i)(B), the agency is proposing to require
that the terms ``dental caries'' or ``tooth decay'' be used in
specifying the disease. These terms are commonly used in dental and
dietary guidance materials and are familiar to consumers.
Under Sec. 101.14(d), a health claim must be complete, truthful,
and not misleading. It must enable the public to comprehend the
information provided and to understand the relative significance of
such information in the context of a total daily diet. In addition, a
health claim may not attribute any specific degree of reduction in risk
of disease from consumption of the product.
In recognition of these general requirements, and in light of the
fact that both environmental and genetic factors, as well as eating
behaviors, all affect a person's risk of developing dental caries (see
proposed Sec. 101.80(a)(1)), FDA is proposing in
Sec. 101.80(c)(2)(i)(C) that for packages that have a total surface
area available for labeling of 15 or more square inches, the claim must
state that dental caries depends on many factors.
FDA is aware that many sugar alcohol-containing chewing gum and
confectionery products have a total surface area available for labeling
of less than 15 square inches, however. Such a small area would
preclude the use of a health claim that included all of the required
elements. Many of these products, packaged in small packages, have used
the claim ``useful only in not promoting dental caries'' on their
labels for more than 15 years. Because of the potential dental health
benefits to consumers resulting from a positive action on this proposal
and given the unique history of this claim, the agency tentatively
finds that continued use of an abbreviated claim on packages with less
than 15 square inches of surface area will not be misleading or
confusing
[[Page 37526]]
to consumers of these products. However, the agency continues to
believe that the fact that dental caries are multifactorial in their
etiology is fundamental to an understanding of the claim. Therefore,
the agency tentatively concludes that this fact is a material fact, and
that it must be disclosed on packages with space available for labeling
of 15 or more square inches. In Sec. 101.80(c)(2)(i)(D), given the
unique circumstances surrounding this claim, FDA is proposing to exempt
packages with a total surface area available for labeling of less than
15 square inches from the provisions of Sec. 101.80(c)(2)(i)(C).
In proposed Sec. 101.80(c)(2)(i)(E), FDA states that the claim must
not attribute any degree of nonpromotion of dental caries to the use of
the sugar alcohol-containing food. Based on the agency's review of
human and animal studies in this document, none of the studies provide
a basis for determining the percent reduction in risk of dental caries
from consuming sugar alcohol-containing foods. This requirement is also
consistent with the general requirements for health claims in
Sec. 101.14(d), and those health claims authorized under part 101,
subpart E.
D. Nature of the Food
In Sec. 101.80(c)(2)(ii)(A), FDA is proposing to require that the
food bearing this health claim meet the requirement in
Sec. 101.60(c)(1)(i) with respect to sugars content, that is, qualify
to bear the claim ``sugar free.'' This requirement is consistent with
the scientific evidence showing that foods with a mixture of sugar
alcohols and sugars are still acidogenic (Ref. 38) and cariogenic
(Refs. 52, 55, and 56, for examples).
In new Sec. 101.80(c)(2)(ii)(B), the agency is proposing that the
sugar alcohols be limited to xylitol, sorbitol, mannitol, maltitol,
isomalt, lactitol, HSH, HGS, or a combination of these. This
requirement reflects the available scientific evidence on the sugar
alcohols and their effects on the promotion of dental caries.
Sugar alcohols in combination with high intensity sugar
substitutes, such as aspartame and saccharin, are also used to replace
sucrose. The agency notes that under proposed Sec. 101.80(c)(2)(ii)(A)
and (c)(2)(ii)(B), a sugar alcohol and dental caries claim could appear
on a food that contains a combination of sugar alcohols and high
intensity sweeteners but no sugars. The agency notes that high
intensity sweeteners are not considered fermentable by oral bacteria
(Ref. 75).
The agency is not specifying a level of sugar alcohols in the food
product because these ingredients are being used as a substitute for
sugars. Therefore, the amount of the substance required is that needed
to achieve a desired level of sweetness.
In new Sec. 101.80(c)(2)(ii)(C), the agency is proposing that to
qualify to bear a claim, the sugar alcohol-containing food, when tested
for its effects on plaque pH using in vivo methods, must not lower
plaque pH below 5.7. Based on the agency's review of the scientific
evidence, foods that lowered plaque pH below 5.5 were contributing to
an acidic environment in the mouth that is detrimental to tooth enamel.
Although a ``critical'' plaque pH has not been defined, changes in pH
to a minimum that is above 5.5 are generally considered above the level
where enamel decalcification would be promoted (Refs. 8, 75, 86, and
87).
In its review of the scientific evidence, the agency noted that
sugar alcohol-containing chewing gum and confectioneries, such as
mints, that do not contain fermentable carbohydrates, did not lower
plaque pH below 5.5. However, in one study that evaluated the
cariogenic potential of an experimental licorice that contained soy
flour, the soy flour was shown to be highly fermentable and dropped
plaque pH to below 5.5 (Ref. 43). The agency is concerned that use of
sugar alcohols in a food product that contains an ingredient, such as
refined flour, that would cause plaque pH to drop below 5.5 would thus
cause the food to be cariogenic.
In the Swiss ``zahnschonend'' program, if a food does not promote a
drop in plaque pH, using intraoral plaque pH telemetric tests, below
5.7 by bacterial fermentation either during consumption or up to 30 min
later, the food is considered ``safe for teeth'' and may be labeled as
such (Ref. 75). The intraoral plaque pH telemetric test is an in vivo
method that measures the acidogenicity of foods and dietary patterns.
Based on experience and experimentation, foods judged by the Swiss
program to be safe for teeth are those that have been shown not to
promote dental decay in animal or human model systems (Ref. 75).
In this proposed rule, FDA is proposing to require in
Sec. 101.80(c)(2)(ii)(C) that to be eligible to bear the claim, the
food product not lower plaque pH below 5.7, based on in vivo
measurements, during the time food is consumed and for up to 30 min
after the food is consumed. The agency is proposing a more conservative
value than pH 5.5 because such a value gives assurance that, consistent
with the health claim, the food will not promote dental caries.
The methods that have been described as the most suitable for
assessing plaque acidity of dietary constituents in humans are
indwelling electrode systems, such as the intraoral plaque pH
telemetric test used in the Swiss program (Refs. 8 and 75). ICT's (Ref.
88), which incorporate enamel blocks into dental appliances for the
production of carious lesions when used in combination with intraoral
plaque pH telemetry, are also good methods for assessing changes in
plaque pH in response to food. The agency is asking for comments on
whether establishing a minimum plaque pH that is measured in vivo
during consumption and up to 30 min following consumption is a
reasonable approach to use to determine whether a sugar alcohol-
containing food, other than sugar alcohol-containing chewing gum and
confectioneries, that contains other carbohydrate ingredients is in
compliance with any final rule resulting from this proposal.
E. Optional Information
FDA is proposing in new Sec. 101.80(d)(1), consistent with the
regulations that have authorized other health claims, that health
claims about the relationship between sugar alcohols and dental caries
may provide additional information that is drawn from proposed
Sec. 101.80 (a) and (b).
In new Sec. 101.80(d)(2), the agency is proposing that when
referring to sucrose, the claim may use the term ``sucrose'' or
``sugar.'' The use of either of these terms is consistent with FDA's
regulation that affirms that use of this substance is GRAS
(Sec. 184.1854).
FDA is proposing in Sec. 101.80(d)(3), consistent with the health
claims that it has already authorized under part 101, subpart E, to
allow manufacturers to provide additional information about risk
factors associated with the development of dental caries. Although
sugars consumption and infection with S. mutans are often identified as
the cause of dental caries, there are several risk factors that play
significant roles in the etiology of this disease (Ref. 71). These
factors include frequent consumption of sucrose or other fermentable
carbohydrates, presence of oral bacteria capable of fermenting sugars,
length of time sugars are in contact with the teeth, lack of exposure
to fluoride, individual susceptibility, socioeconomic and cultural
factors, and characteristics of tooth enamel, saliva, and plaque (Refs.
7, 71, and 89).
[[Page 37527]]
F. Model Health Claims
In proposed Sec. 101.80(e), FDA is providing model health claims to
illustrate the requirements of new Sec. 101.80. FDA emphasizes that
these model health claims are illustrative only. If the agency
authorizes claims about the relationship between sugar alcohols and
dental caries, manufacturers will be free to design their own claim so
long as it is consistent with Sec. 101.80(c).
VII. Environmental Impact
The agency has determined under 21 CFR 25.24 (a)(11) that this
action is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
VIII. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354).
Executive Order 12866 directs agencies to assess all costs and benefits
of available regulatory alternatives and, when regulation is necessary,
to select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). The agency believes that
this proposed rule is consistent with the regulatory philosophy and
principles identified in the Executive Order. In addition, the proposed
rule is not a significant regulatory action as defined by the Executive
Order and so is not subject to review under the Executive Order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because it enables firms to make claims that they
would otherwise be prohibited from making, the agency certifies that
the proposed rule will not have a significant economic impact on a
substantial number of small entities. Therefore, under the Regulatory
Flexibility Act, no further analysis is required.
IX. Effective Date
FDA is proposing to make these regulations effective 30 days after
the publication of a final rule based on this proposal.
X. Comments
Interested persons may, on or before October 3, 1995, submit to the
Dockets Management Branch (HFA-305), Food and Drug Administration, rm.
1-23, 12420 Parklawn Dr., Rockville, MD 20857, written comments
regarding this proposal. Two copies of any comments are to be
submitted, except that individuals may submit one copy. Comments are to
be identified with the docket number found in brackets in the heading
of this document. Received comments may be seen in the office above
between 9 a.m. and 4 p.m., Monday through Friday.
XI. 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. Drozen, Melvin S., ``Health claim petition regarding the
noncariogenicity of sugar alcohols,'' August 31, 1994.
2. Drozen, Melvin S., ``Objections and request for a hearing by
Working Group of sugar alcohol manufacturers to the revocation of 21
C.F.R. section 105.66(f),'' Docket No. 91N-384L, Dockets Management
Branch, FDA, Rockville, MD.
3. Saltsman, Joyce J., CFSAN, FDA, Letter to Melvin S. Drozen,
September 15, 1994.
4. Saltsman, Joyce J., CFSAN, FDA, Letter to Melvin S. Drozen,
October 7, 1994.
5. Drozen, Melvin S., Letter to FDA, November 15, 1994.
6. Saltsman, Joyce J., CFSAN, FDA, Memorandum of telephone
conversation, December 8, 1994.
7. DHHS, Public Health Service (PHS), ``The Surgeon General's
Report on Nutrition and Health,'' U.S. Government Printing Office,
Washington, DC, 1988.
8. Harper, D. S., D. C. Abelson, and M. E. Jensen, ``Human plaque
acidity models,'' Journal of Dental Research, 65 (Special Issue):1503-
1510, 1986.
9. Ten Cate, J. M., ``Demineralization models: Mechanistic aspects
of the caries process with special emphasis on the possible role of
foods,'' Journal of Dental Research, 65 (Special Issue):1511-1515,
1986.
10. Curzon, M. E. J., ``Integration of methods for determining the
cariogenic potential of foods: Is this possible with present
technologies?,'' Journal of Dental Research, 65 (Special Issue):1520-
1524, 1986.
11. Stookey, G. K., ``Considerations in determining the cariogenic
potential of foods: How should existing knowledge be combined?,''
Journal of Dental Research, 65(Special Issue):1525-1527, 1986.
12. Working Group Consensus Report, ``Integration of methods,''
Journal of Dental Research, 65(Special Issue):1537-1539, 1986.
13. DePaola, D. P., ``Executive summary,'' Scientific Consensus
Conference on Methods for Assessment of the Cariogenic Potential of
Foods, Journal of Dental Research, 65(Special Issue)1540-1543, 1986.
14. LSRO, FASEB, ``Dietary Sugars in Health and Disease, II.
Xylitol,'' Bethesda, MD, July, 1978.
15. LSRO, FASEB, ``Dietary Sugars in Health and Disease, III.
Sorbitol,'' Bethesda, MD, July, 1978.
16. LSRO, FASEB, ``Dietary Sugars in Health and Disease, IV.
Mannitol,'' Bethesda, MD, July, 1978.
17. Working Group Consensus Report, ``Animal caries,'' Journal of
Dental Research, 65:1528-1529, 1986.
18. Working Group Consensus Report, ``Human plaque acidity,''
Journal of Dental Research, 65:1530-1531, 1986.
19. Working Group Consensus Report, ``Demineralization/
remineralization,'' Journal of Dental Research, 65:1532-1536, 1986.
20. Moller, I. J., and S. Poulsen, ``The effect of sorbitol-
containing chewing gum on the incidence of dental caries, plaque and
gingivitis,'' Community Dental and Oral Epidemiology, 1:58-67, 1973.
21. Banozcy, J., E. Hadas, I. Esztary, I. Marosi, and J. Nemes,
``Three-year results with sorbitol in clinical longitudinal
experiments,'' Journal of the International Association of Dentistry in
Children, 12:59-63, 1981.
22. Kandelman, D., and G. Gagnon, ``Clinical results after 12
months from a study of the incidence and progression of dental caries
in relation to consumption of chewing-gum containing xylitol in school
preventive programs,'' Journal of Dental Research, 66:1407-1411, 1987.
23. Rekola, M., ``Changes in buccal white spots during two-year
total substitution of dietary sucrose with xylitol,'' Acta Odontologica
Scandinavica, 44:285-290, 1986.
24. Makinen, K. K., and A. Scheinin, ``Turku sugar studies. VI. The
administration of the trial and the control of the dietary regimen,''
Acta Odontologica Scandanavia, 33:105-127, 1975.
25. Rekola, M., ``Approximal caries development during 2-year total
substitution of dietary sucrose with xylitol,'' Caries Research, 21:87-
94, 1987.
26. Scheinin, A., J. Banoczy, J. Szoke, I. Esztari, K.
Pienihakkinen, U. Scheinin, J. Tiekso, P. Zimmerman, and E. Hadas,
``Collaborative WHO xylitol
[[Page 37528]]
field studies in Hungary. I. Three-year caries activity in
institutionalized children,'' Acta Odontologica Scandinavica, 43:327-
347, 1985.
27. Banoczy, J., A. Scheinin, R. Pados, G. Ember, P. Kertesz, and
K. Pienihakkinen, ``Collaborative WHO xylitol field studies in Hungary.
II. General background and control of the dietary regimen,'' Acta
Odontologica Scandinavica, 43:349-357, 1985.
28. Scheinin, A., K. Pienihakkinen, J. Tiekso, J. Banoczy, J.
Szoke, I. Esztari, P. Zimmerman, and E. Hadas, ``Collaborative WHO
xylitol field studies in Hungary. VII. Two-year caries incidence in 976
institutionalized children,'' Acta Odontologica Scandinavica, 43:381-
387, 1985.
29. Barmes, D., J. Barnaud, S. Khambonanda, and J. Sardo Infirri,
``Field trials of preventive regimes in Thailand and French
Polynesia,'' International Dental Journal, 35:66-72, 1985.
30. Kandelman, D., A. Bar, and A. Hefti, ``Collaborative WHO
xylitol field study in French Polynesia. I. Baseline Prevalence and 32-
month caries increment,'' Caries Research, 22:1-10, 1988.
31. Frostell, G., L. Blomlof, I. Blomqvist, G. M. Dahl, S. Edward,
A. Fjellstrom, C. O. Henrikson, O. Larje, C. E. Nord, and K. J.
Nordenvall, ``Substitution of sucrose by Lycasin in candy.
`The Roslagen study','' Acta Odontologica Scandinavica, 32:235-253,
1974.
32. Glass, R. L., ``A two year clinical trial of sorbitol gum,''
Caries Research, 17:365-368, 1983.
33. Ikeda, T., K. Ochiai, Y. Doi, T. Mukasa, and S. Yagi,
``Maltitol and SE58 in rats and decalcification as human intraoral
substrate, Nihon University Journal of Oral Science, 25:1-5, 1975.
34. Yagi, S., ``Effects of maltitol on insoluble glucan synthesis
by S. mutans and change of enamel hardness,'' Nihon University Journal
of Oral Science, 4:136-144, 1978.
35. Leach, S. A., G. T. R. Lee, and W. M. Edgar, ``Remineralization
of artificial caries-like lesions in human enamel in situ by chewing
sorbitol gum,'' Journal of Dental Research, 68:1064-1068, 1989.
36. Rundegren, J., T. Koulourides, and T. Ericson, ``Contribution
of maltitol and Lycasin to experimental enamel demineralized
in the human mouth,'' Caries Research, 14:67-74, 1980.
37. Creanor, S. L., R. Strang, W. H. Gilmour, R. H. Foye, J. Brown,
D. A. M. Geddes, and A. F. Hall, ``The effect of chewing gum use on in
situ enamel lesion remineralization,'' Journal of Dental Research,
71:1895-1900, 1992.
38. Bibby, B. G., and J. Fu, ``Changes in plaque pH in vitro by
sweeteners,'' Journal of Dental Research, 64:1130-1133, 1985.
39. Birkhed, D., and S. Edwardsson, ``Acid production from sucrose
substitutes in human dental plaque,'' Proceedings of ERGOB Conference,
pp. 211-217, 1978.
40. Birkhed, D., S. Edwardsson, B. Svensson, F. Moskovitz, and G.
Frostell, ``Acid production from sorbitol in human dental plaque,''
Archives of Oral Biology, 23:971-975, 1978.
41. Birkhed, D., S. Edwardsson, M. L. Ahlden, and G. Frostell,
``Effects of 3 mo frequent consumption of hydrogenated starch
hydrolysate (Lycasin), maltitol, sorbitol and xylitol on human dental
plaque,'' Acta Odontologica Scandinavica, 37:103-115, 1979.
42. Frostell, G., ``Dental plaque pH in relation to intake of
carbohydrate products,'' Acta Odontologica Scandanavia, 27:3-29, 1969.
43. Toors, F. A., and J. I. B. Herczog, ``Acid production from a
nonsugar licorice and different sugar substitutes in Streptococcus
mutans monoculture and pooled plaque-saliva mixtures,'' Caries
Research, 12:60-68, 1978.
44. Gallagher, I. H., and S. J. Fussell, ``Acidogenic fermentation
of pentose alcohols by human dental plaque microorganisms,'' Archives
of Oral Biology, 24:673-679, 1979.
45. Gehring, F., and H. D. Hufnagel, ``Intra- and extraoral pH
measurements on human dental plaque after rinsing with some sugar and
sucrose substitute solutions,'' Oralprophylaxe, 5:13-19, 1983.
46. Havenaar, R., J. H. J. Huis In't Veld, O. Backer Dirks, and J.
D. de Stoppelaar, ``Some bacteriological aspects of sugar
substitutes,'' Proceedings from ERGOB Conference, pp. 192-196, 1978.
47. Jensen, M. E., ``Human plaque acidogenicity studies with
hydrogenated starch hydrolysates,'' unpublished.
48. Maki, Y., K. Ohta, I. Takazoe, Y. Matsukubo, Y. Takaesu, V.
Topitsoglou, and G. Frostell, ``Acid production from isomaltulose,
sucrose, sorbitol, xylitol in suspensions of human dental plaque,''
Caries Research, 17:335-339, 1983.
49. Park, K. K., B. R. Schemehorn, J. W. Bolton, and G. K. Stookey,
``Comparative effect of sorbitol and xylitol mints on plaque
acidogenicity,'' presented at the International Association for Dental
Research, April 17-21, 1991.
50. Soderling, E., K. K. Makinen, C.-Y. Chen, H. R. Pape, and P.-L.
Makinen, ``Effect of sorbitol, xylitol and xylitol/sorbitol gums on
dental plaque,'' Caries Research, 23:378-384, 1989.
51. Birkhed, D., and G. Skude, ``Relation of amylase to starch and
Lycasin metabolism in human dental plaque in vitro,''
Scandinavian Journal of Dental Research, 86:248-258, 1978.
52. Havenaar, R., J. S. Drost, J. D. de Stoppelaar, J. H. J. Huis
in't Veld, and O. Backer Dirks, ``Potential cariogenicity of Lycasin
80/55 in comparison to starch, sucrose, xylitol, sorbitol and L-sorbose
in rats,'' Caries Research, 18:375-384, 1984.
53. Havenaar, R., J. S. Drost, J. H. J. Huis in't Veld, O. Backer
Dirks, and J. D. de Stoppelaar,, ``Potential cariogenicity of Lycasin
80/55 before and after repeated transmissions of the dental plaque
flora in rats,'' Archives of Oral Biology, 29:993-999, 1984.
54. Havenaar, R., J. H. J. Huis In't Veld, J. D. de Stoppelaar, and
O. Backer Dirks, ``A purified cariogenic diet for rats to test sugar
substitutes with special emphasis on general health,'' Caries Research,
17:340-352, 1983.
55. Havenaar, R., J. D. Huis in't Veld, J. D. J. de Stoppelaar, and
O. B. Dirks, ``Anti-cariogenic and remineralizing properties of xylitol
in combination with sucrose in rats inoculated with Streptococcus
mutans,'' Caries Research, 18:269-277, 1984.
56. Grenby, T. H., and J. Colley, ``Dental effects of xylitol
compared with other carbohydrates and polyols in the diet of laboratory
rats,'' Archives of Oral Biology, 28:745-758, 1983.
57. Karle, E. J., and F. Gehring, ``Kariogenitatsuntersuchungen von
zuckeraustauschstoffen an xerostomierlen ratten. (Studies on the
cariogenesis of sugar substitutes in xerostomized rats),'' Deutsche
Zahnarztliche Zeitschrift, 34:551-554, 1979.
58. Muhlemann, H. R., R. Schmid, T. Noguchi, T. Imfeld, and R. S.
Hirsch, ``Some dental effects of xylitol under laboratory and in vivo
conditions,'' Caries Research, 11:263-276, 1977.
59. Shyu, K.-W., and M.-Y Hsu, ``The cariogenicity of xylitol,
mannitol, sorbitol and sucrose,'' Proceedings of the National Science
Council ROC, 4:21-26, 1980.
60. Bramstedt, F., F. Gehring, and E. J. Karle, ``Comparative study
of the cariogenic effects of Palatinit, xylitol and
saccharose in animals,'' unpublished, 1976.
61. Izumiya, A., T. Ohshima, and S. Sofue, ``Caries inducibility of
various sweeteners,'' Academy of Pedodontia, p. 65, May 1984.
62. Gehring, F., and E. J. Karle, ``The sugar substitute
Palatinit with special emphasis on microbiological and
caries-preventing aspects,'' Zeitschrift Ernahrungswiss, 20:96-106,
1981.
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63. Karle, E. J., and F. Gehring, ``Palatinit-A New Sugar
Substitute and its Carioprophylactic Assessment,'' Deutsche
Zalnarztliche Zeitschrift 33:189-191, 1978.
64. Larje, O., and R. H. Larson, ``Reduction of dental caries in
rats by intermittent feeding with sucrose substitutes, Archives of Oral
Biology, 15:805-816, 1970.
65. Muhlemann, H. R., ``Effect of topical application of sugar
substitutes on bacterial agglomerate formation, caries incidence and
solution rates of molars in the rat,'' unpublished, 1978.
66. Ooshima, T., A. Izumitani, T. Minami, T. Yoshida, S. Sobue, T.
Fujiwari, and S. Hamada, ``Non-cariogenicity of maltitol in SPF rats
infected with mutans streptococci,'' submitted for publication.
67. Tate, N., S. Wada, H. Tani, and K. Oikawa, ``Experimental
studies on correlations between progressive caries and sugar intake,''
unpublished.
68. Leach, S. A., and R. M. Green, ``Effect of xylitol-supplemented
diets on the progression and regression of fissure caries in the albino
rat,'' Caries Research, 14:16-23, 1980.
69. Mukasa, T., ``The possibility of maltitol and SE 58 as non-
cariogenic sweeteners: their utilization by Streptococcus mutans for
insoluble glucan synthesis and experimental dental caries in rats,''
Nihon University Journal of Oral Science, 3:266-275, 1977.
70. Hoeven, J. S. van der, ``Cariogenicity of disaccharide alcohols
in rats,'' Caries Research, 14:61-66, 1980.
71. Burt, B. A., and A. I. Ismail, ``Diet, nutrition, and food
cariogenicity,'' Journal of Dental Research, 65 (Special Issue): 1475-
1484, 1986.
72. National Research Council, National Academy of Sciences, ``Diet
and Health,'' National Academy Press, Washington, DC, 1989.
73. Hoeven, J.S. van der, ``Carigenicity of lactitol in program-fed
rats,'' Caries Research, 20:441-443, 1986.
74. Imfeld, T., and H. R. Muhlemann, ``Cariogenicity and
acidogenicity of food, confectionery and beverages,'' Pharmacology and
Therapeutic Dentistry, 3:53-68, 1978.
75. Imfeld, T., ``Identification of Low Caries Risk Dietary
Components,'' Monographs in Oral Science, vol. 11, Karger, Basel,
Switzerland, pp. 1-8 and 117-144, 1983.
76. Grenby, T. H., A. Phillips, and M. Mistry, ``Studies of the
dental properties of lactitol compared with five other bulk sweeteners
in vitro,'' Caries Research, 23:315-319, 1989.
77. Grenby, T. H., and A. Phillips, ``Dental and metabolic effects
of lactitol in the diet of laboratory rats,'' British Journal of
Nutrition, 61:17-24, 1989.
78. Edgar, W. M., and D. A. M. Geddes, ``Plaque acidity models for
cariogenicity testing--some theoretical and practical observations,''
Journal of Dental Research, 65 (Special Issue): 1498-1502, 1986.
79. Birkhed, D., S. Kalfas, G. Svensater, and S. Edwardsson,
``Microbiological aspects of some caloric sugar substitutes,''
International Dental Journal, 35:9-17, 1985.
80. Schrotenboer, G. H., ``In the Matter of Revising the Regulation
for Foods for Special Dietary Uses,'' Docket No. FDC-78, March 4, 1970
at 6-7.
81. Saltsman, Joyce J., CFSAN, FDA, Memorandum to file--
Environmental Assessment of Health Claim Petition, December 23, 1994.
82. Ayers, C. S., and R. A. Abrams, ``Noncariogenic sweeteners,
sugar substitutes for caries control,'' Dental Hygiene, April, 162-
167:1987.
83. Rugg-Gunn, A. J., and W. M. Edgar, ``Sweeteners and dental
health,'' Community Dental Health, 2:213-223, 1985.
84. Grenby, T. H., ``Nutritive sucrose substitutes and dental
health,'' In: Developments in Sweeteners, editors: T. H. Grenby, K. J.
Parker, and M. G. Lindley, Elsevier Science, Inc., 2:51-88, 1983.
85. Rugg-Gunn, A. J., ``Lycasin and the prevention of
dental caries,'' In: Progress in Sweeteners, editor: T. H. Grenby,
Elsevier Science, Inc., pp. 311-328, 1989.
86. Loesche, W. J., ``The rationale for caries prevention through
use of sugar substitutes,'' International Dental Journal, 35:1-8, 1985.
87. Mandel, I. D., ``Dental caries,'' American Scientist, 67:680-
688, 1979.
88. Koulourides, T., R. Bodden, S. Keller, L. Manson-Hing, J.
Lastra, and T. Housch, ``Cariogenicity of nine sugars tested with an
intraoral device in man,'' Caries Research 10:427-441, 1976.
89. Baer, A., ``Significance and promotion of sugar substitution
for the prevention of dental caries,'' Lben.-Wiss U. Technology,
Academic Press, 22:46-53, 1989.
90. LSRO, FASEB ``Health Aspect of Sugar Alcohols and Lactose,''
Bethesda, MD, December 1986.
91. Joint FAO/WHO Expert Committee on Food Additives, ``Evaluation
of Certain Food Additives and Contaminants,'' Geneva, Switzerland, pp.
16-17, 1993.
List of Subjects in 21 CFR Part 101
Food labeling, Nutrition, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 101 be amended as follows:
PART 101--FOOD LABELING
1. The authority citation for 21 CFR part 101 is revised to read as
follows:
Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act
(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342,
343, 348, 371).
2. New Sec. 101.80 is added to subpart E to read as follows:
Sec. 101.80 Health claims: dietary sugar alcohols and dental caries.
(a) Relationship between dietary sugar alcohols and dental caries.
(1) Dental caries, or tooth decay, is a disease caused by many factors.
Both environmental and genetic factors can affect the development of
dental caries. Risk factors include tooth enamel crystal structure and
mineral content, plaque quantity and quality, saliva quantity and
quality, individual immune response, types and physical characteristics
of foods consumed, eating behaviors, presence of acid producing oral
bacteria, and cultural influences.
(2) The relationship between dietary sugars consumption and tooth
decay is well established. Sucrose is one of the most, but not the
only, cariogenic sugar in the diet. Bacteria found in the mouth are
able to metabolize sugars producing acid and forming dental plaque.
Prolonged exposure of the tooth enamel to acids from dental plaque
causes tooth enamel to demineralize, or decay. Frequent between-meal
consumption of sugary foods, particularly foods that easily stick to
the teeth, can cause tooth decay.
(3) U.S. diets tend to be high in sugars consumption. Although
there has been a decline in the prevalence of dental caries in the
United States, per capita consumption of sugars has not declined, and
the disease remains widespread throughout the population. Federal
government agencies and nationally recognized health professional
organizations recommend decreased consumption of sugars.
(4) Dietary sugar alcohols can be used to replace dietary sugars in
food. Sugar alcohols are significantly less cariogenic than dietary
sugars. Thus, replacing dietary sugars with sugar alcohols helps to
maintain dental health.
(b) Significance of the relationship between sugar alcohols and
dental caries. Sugar alcohols do not promote
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dental caries because they are slowly metabolized by bacteria to form
some acid. The rate and amount of acid production is significantly less
than that from sucrose and does not cause the loss of important
minerals from tooth enamel.
(c) Requirements. (1) All requirements set forth in Sec. 101.14
shall be met, except that sugar alcohol-containing foods are exempt
from section Sec. 101.14(e)(6).
(2) Specific requirements. (i) Nature of the claim. A health claim
relating sugar alcohols and the nonpromotion of dental caries may be
made on the label or labeling of a food described in (c)(2)(ii) of this
section, provided that:
(A) The claim shall state ``does not promote,'' ``useful in not
promoting,'' or ``expressly for not promoting'' dental caries.
(B) In specifying the disease, the claim uses the following terms:
``dental caries'' or ``tooth decay.''
(C) For packages with a total surface area available for labeling
of 15 or more square inches, the claim shall indicate that dental
caries depends on many factors.
(D) Packages with a total surface area available for labeling of
less than 15 square inches are exempt from paragraph (C) of this
section.
(E) The claim shall not attribute any degree of nonpromotion of
dental caries to the use of the sugar alcohol-containing food.
(ii) Nature of the food. (A) The food shall meet the requirement in
Sec. 101.60(c)(1)(i) with respect to sugars content.
(B) The sugar alcohol in the food shall be xylitol, sorbitol,
mannitol, maltitol, isomalt, lactitol, hydrogenated starch
hydrolysates, hydrogenated glucose syrups, or a combination of these.
(C) The sugar alcohol-containing food shall not lower plaque pH
below 5.7 by bacterial fermentation either during consumption or up to
30 minutes after consumption, as measured by in vivo tests.
(d) Optional information. (1) The claim may include information
from paragraphs (a) and (b) of this section, which describe the
relationship between diets containing sugar alcohols and dental caries.
(2) In referring to sucrose, the claim may use the term ``sucrose''
or ``sugar.''
(3) The claim may identify one or more of the following risk
factors for dental caries: Frequent consumption of sucrose or other
fermentable carbohydrates; presence of oral bacteria capable of
fermenting sugars; length of time sugars are in contact with the teeth;
lack of exposure to fluoride; individual susceptibility; socioeconomic
and cultural factors; and characteristics of tooth enamel, saliva, and
plaque.
(e) Model health claim. The following model health claims may be
used in food labeling to describe the relationship between sugar
alcohol and dental caries.
(1) For packages with total surface area available for labeling of
less than 15 square inches:
(i) Useful only in not promoting tooth decay;
(ii) Does not promote tooth decay; and
(iii) [This product] does not promote tooth decay.
(2) For packages with total surface area available for labeling of
15 or more square inches:
(i) Tooth decay is a disease caused by many factors including
frequent between meal consumption of sugary foods. [Name of sugar
alcohol] does not promote tooth decay.
(ii) [Reserved].
Dated: July 7, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
Note: The following tables will not appear in the annual Code of
Federal Regulations.
BILLING CODE 4160-01-P
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[FR Doc. 95-17505 Filed 7-19-95; 8:45 am]
BILLING CODE 4160-01-C