[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=""><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=""><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="">6), 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=""><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)="">< 0.05),="" and="" each="" xylitol="" group="" had="" significantly=""><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=""><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=""><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=""><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=""><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=""><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=""><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=""><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=""><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=""><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=""><0.001) fewer="" sulcal="" caries="" compared="" to="" the="" sucrose="" group.="" the="" results="" of="" experiment="" 3="" showed="" significantly=""><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=""><0.001) fewer="" caries="" than="" the="" sucrose="" group="" (group="" l).="" groups="" d="" through="" i="" and="" k="" reported="" significantly=""><0.001 and=""><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=""><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=""><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=""><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=""> in candy.
`The Roslagen study','' Acta Odontologica Scandinavica, 32:235-253,
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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,
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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.
[[Page 37529]]
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.
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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
[[Page 37530]]
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
