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Gastrointestinal Disturbances Associated with the Consumption of Sugar Alcohols with Special Consideration of Xylitol: Scientific Review and Instructions for Dentists and Other Health-Care Professionals

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Sugar alcohols (polyols) are used in food manufacturing and in medical tests and examinations. d-Glucitol (sorbitol) and d-mannitol were previously the most common alditols used for these purposes. After the 1960s, xylitol became a common ingredient in noncariogenic confectioneries, oral hygiene products, and diabetic food. Erythritol, a polyol of the tetritol type, can be regarded as the sweetener of the "next generation." The disaccharide polyols maltitol, lactitol, and isomalt have also been used in food manufacturing and in medical tests. Consumption of pentitol- and hexitol-type polyols and disaccharide polyols may cause gastrointestinal disturbances at least in unaccustomed subjects. The occurrence of disturbances depends on consumer properties and on the molecular size and configuration of the polyol molecule. Adaptation may take place as a result of enzyme induction in the intestinal flora. Some of the literature on xylitol has been difficult to access by health-care professionals and will be reviewed here. Research and clinical field experience have found no pathology in polyol-associated osmotic diarrhea-the intestinal mucosa having normal basic structure, except in extreme instances. Xylitol is better tolerated than hexitols or the disaccharide polyols. Erythritol, owing to its smaller molecular weight and configuration that differ from other alditols, normally avoids the gastrointestinal reactions encountered with other polyols. This review will also touch upon the FODMAPs diet concept.
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Review Article
Gastrointestinal Disturbances Associated with
the Consumption of Sugar Alcohols with Special Consideration
of Xylitol: Scientific Review and Instructions for Dentists and
Other Health-Care Professionals
Kauko K. Mäkinen
Institute of Dentistry, University of Turku, Lemmink¨
aisenkatu 2, 20520 Turku, Finland
Correspondence should be addressed to Kauko K. M¨
akinen; kauko.makinen@uusikaupunki.
Received  June ; Revised  September ; Accepted  September 
Academic Editor: Vincent Everts
Copyright ©  Kauko K. M¨
akinen. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sugar alcohols (polyols) are used in food manufacturing and in medical tests and examinations. -Glucitol (sorbitol) and -
mannitol were previously the most common alditols used for these purposes. Aer the s, xylitol became a common ingredient
in noncariogenic confectioneries, oral hygiene products, and diabetic food. Erythritol, a polyol of the tetritol type, can be regarded
as the sweetener of the “next generation.” e disaccharide polyols maltitol, lactitol, and isomalt have also been used in food
manufacturing and in medical tests. Consumption of pentitol- and hexitol-type polyols and disaccharide polyols may cause
gastrointestinal disturbances at least in unaccustomed subjects. e occurrence of disturbances depends on consumer properties
and on the molecular size and conguration of the polyol molecule. Adaptation may take place as a result of enzyme induction in the
intestinal ora. Some of the literature on xylitol has been dicult to access by health-care professionals and will be reviewed here.
Research and clinical eld experience have found no pathology in polyol-associated osmotic diarrhea—the intestinalmucosa having
normal basic structure, except in extreme instances. Xylitol is better tolerated than hexitols or the disaccharide polyols. Erythritol,
owing to its smaller molecular weightand conguration that dier from other alditols, normally avoids the gastrointestinal reactions
encountered with other polyols. is review will also touch upon the FODMAPs diet concept.
1. Introduction
e use of sugar alcohols (polyols) in the manufacturing of
foods, medicines, and oral hygiene products has increased
considerably during the past decades. Examples of more fre-
quently used polyols include simple alditols such as erythr itol,
xylitol, -glucitol (sorbitol), and -mannitol and disaccha-
ride sugar alcohols such as maltitol, lactitol, and isomalt.
Sugar alcohols have been used in surprisingly numerous
medical, cosmetic, techno-chemical, and similar applica-
tions. Xylitol-based infusion therapy currently comprises one
of the largest single applications of this alditol []. Xylitol-
containingchewinggumshavealsobeenemployedinvarious
medical studies related to cognitive function, mastication,
drug delivery, physiologic tests, and others [].
Xylitoland-glucitolareusedinchewinggumsand
troches aimed at reducing the incidence of dental caries [].
Physiologically and physicochemically, these substances are
normally absorbed slowly from the intestinal lumen and
may cause so-called osmotic diarrhea in some individuals
if the amounts consumed are too high []. Such symptoms
may occur especially in subjects unaccustomed to sugar
alcohols, as has been found already since s [–]. e
occurrence of diarrhea, however, depends on a multitude
of factors such as the person’s weight, the composition and
structure of the rest of the simultaneously consumed diet
[, ], state of fasting, the type of food that contains the
sugar alcohols (liquid and solid consumables normally have
dierent eects) [], and other factors []. What is even
more decisive is the molecular structure of the ingested sugar
alcohol. e size and symmetry of the sugar alcohol molecule,
and the number of hydroxyl groups present in the molecule,
signicantly inuence the behavior of each sugar alcohol
along the entire length of the alimentary tract. It is possible
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International Journal of Dentistry
Volume 2016, Article ID 5967907, 16 pages
http://dx.doi.org/10.1155/2016/5967907
International Journal of Dentistry
that these causative factors are not known to all health-care
workers.
Despite the many positive eects of sugar alcohols, their
consumption is frequently linked also to irritable bowel
syndrome (IBS) and abnormal atulence [, ], which aect
quality of life negatively and result in a considerable economic
burden in terms of health-care costs. However, it has become
evident that sugar alcohols can be benecial in the treatment
of chronic constipation []; for example, -glucitol has been
exploited in several commercial preparations. erefore, den-
tists, physicians, and other health-care workers should be
made to understand where to focus t heir attention when com-
municating with patients, detecting false opinions and mis-
conceptions about diarrhea, atulence, IBS, and constipation,
and correcting them on the basis of scientic evidence and
long-term clinical experience. Tuck et al. [], Xiao et al.
[], and other authors have provided information on the gut
function-enhancing eects of “indigestible sugars” (i.e., sugar
alcohols and certain oligosaccharides) [, , , –]. ese
aspects are represented in this review by older German publi-
cations [, ] and those from the former Soviet Union []
(vide infra).
No previous dental article has specically focused on
osmotic diarrhea associated with excessive consumption of
sugar alcohols. Consequently, the primary objective of this
article is to review the gastrointestinal research carried out
with sugar alcohols with special consideration of simple
dietary alditols which have been used principally for dental
purposes. Because xylitol has been used for decades in
consumer products favored by children—in ever-increasing
amounts—this review will especially focus on the experience
gathered with xylitol in clinical feeding studies. Some of
the older scientic literature on xylitol has been dicult to
access by regular health-care workers and will be reviewed
here. Erythritol, “the next-generation” sweetener of a tetritol
nature, will be concisely discussed owing to its generally
recognized gastrointestinal safety []. e newly developed
FODMAPs concept will also be touched upon. It is necessary
to emphasize that osmotic diarrhea occasioned by excessive
consumption of carbohydrates and polyols is not a disease,
but rather a simple physicochemical response of the intestinal
tract to the presence of slowly absorbed carbohydrates or
polyols in the gut lumen.
2. Physicochemical Considerations and
Introduction of the FODMAPs Concept
In the systematic chemical nomenclature sorbitol is called
-glucitol. is term will be used in the present text since
thepresenceofthismoleculeinthestructureofcertaindis-
accharide sugar alcohols is most appropriately depicted using
the ocial chemical term. e symmetric xylitol molecule
should not be written with either the  or  prex. For meso-
erythritol or i-erythritol, the simple term erythritol will be
used. Mannitol requires a  or . For the present purpose,
glucose, galactose, and fructose are shown without specifying
the conguration (i.e., ), unless the names appear in those
of disaccharide sugar alcohols.
When a person consumes solutions containing excessive
amounts of carbohydrates and polyols (or salt), water can
draw from the body into the gut lumen, causing osmotic diar-
rhea. is can naturally also result from a disease condition
(such as pancreatic disease). Although the present review will
focus only on cases with osmotic diarrhea that may occur in
healthy subjects who consume excessive quantities of sugar
alcohols, it is necessary to recall that acute osmotic eects
may also result from consuming too great a quantity of pro-
cessed grains and cereals [] and certain fruits and vegetables
[] (vide infra,Section).Inhealthyindividuals,too-large
quantities of common substances such as vitamin C, magne-
sium salts, lactose, and certain antibiotics may cause severe
cases of osmotic diarrhea and bowel distension. Owing to its
simple physical cause, osmotic diarrhea normally stops com-
pletely when the use of the oending agent is discontinued.
Experiments involving oral administration of sugar alco-
hols have normally been carried out using glucose or fructose
as comparisons. It has been found that, in most subjects,
glucose has no laxative eect even in extraordinarily high
dosages.Forfructose,thethresholdofasingledoseis
normally around – g. Fructose represents an important
point of comparison, since consumers’ own judgments as
to the origin of osmotic diarrhea following consumption of
sugar alcohols are oen confused by simultaneous consump-
tion of fructose. e role of fructose and -glucitol in the
etiology of IBS has been somewhat controversial when these
substances are ingested together []. It nevertheless appears
that the degree of symptom provocation is related to the
amounts present in such a mixture but may not be related
directly to the extent of colonic hydrogen production [].
Sugar alcohols behave in the gut lumen in dierent ways,
and their eects are not identical. Sugar alcohol molecules
react in the gut lumen as physical and chemical entities based
on their molecular mass, number of hydroxyl groups present
in the molecule, the spatial orientation of those groups,
and the overall symmetry of the molecule. All common
dietary alditols are characterized by the presence of only two
types of chemical groups, that is, CHOH and CH2OH. e
number of OH groups present in these molecules is shown
in Table , which also reveals how the praxis of expressing
concentrations diers signicantly. ese dierences have
also generated misunderstandings, since most clinical and
nutritional reports customarily give the amount of sugar
alcohols as percentages. e true chemical concentrations can
besignicantlydierent,however.ecaseoferythritoland
sucrose serves as an example. e molarity of sucrose in a
% (w/w) solution is only about one-third of the molarity
of erythritol at the same % concentration. In physiological
studies, it may be preferable to use chemical activities, that is,
the chemical concentrations (molarities), to make the cases
chemically comparable.
e intestinal absorption of xylitol is almost totally
limitedtothemechanismofpermeationwhichappliesto
all strongly hydrophilic substances. e driving force behind
free diusion of xylitol is the direction of the concentration
gradient between the intestinal lumen and the outside com-
partment [, , , –, ]. ese papers have concluded,
among other things, that in case facilitated diusion of xylitol
International Journal of Dentistry
T : Relationship between the molarities and grams per  mL values in aqueous solutions of some dietary sugar alcohols and sucrose.
Sweetener (number of OH
groups in the molecule)
Molecular
weight (g/mole)
Molarity of a %
solution
Molarity of a %
solution Molarity of a % solution
Erythritol (4) . . . .
Xylitol (5) . . . .
Sorbitol (6) . . . .
Mannitol (6) . . . .
Sucrose (8) . . . .
is involved, the transport system must exert very low anity
to xylitol. In free diusion, the uptake of the substance
from the intestinal lumen takes place because of a simple
physicochemical process through the hydrophobic pores in
the membrane. In this process, molecular size is of particular
signicance. is parameter is to a certain extent indicated
by the molecular weight of the substance. It is obvious that
relatively extended molecules are in themselves ill-suited to
the permeation process.
exylitolmoleculeistotallysymmetricalandsmall
compared with the -glucitol molecule whose molar mass
and dimensions are larger and which is also relatively asym-
metrical (in the latter molecule, the hydroxyl groups on C
andCareinthe-conguration).emolarmassandsym-
metry of -mannitol also dier signicantly from those of
xylitol. Hence the consumption of -glucitol and -mannitol
generates far more severe gastrointestinal disturbances than
xylitol. A comparison between the molecular weights of
xylitol (.) and glucose (.) suggests that xylitol absorp-
tion amounts to approximately % of the free diusion
of glucose. In this comparison, the intestinal uptake of -
glucitol (.) may be about % of the absorption of xylitol.
While glucose is virtually completely absorbed in the
upper part of the small intestine, xylitol is normally only
partly absorbed in the upper part and is present in consid-
erable amounts in the lower region of the small intestine.
However, this depends on the quantity of xylitol consumed.
Experience from the Finnish Turku Sugar Studies [, ] also
indicated that xylitol-associated diarrhea can be prevented
by simultaneous administration of bulky food. However,
bulky food does not considerably increase the absorbability
of xylitol, since the preventive eect results primarily from
delayed emptying of the stomach. e presence of plant bers
may bind water, mitigating xylitol-associated diarrhea. As
soon as the causative agent (xylitol) is removed, the tendency
of osmotic diarrhea passes. Also, no irritation is generally
observed in mucous membranes, except in extreme instances.
Total absorption of xylitol and lessened osmotic diarrhea are
more likely to occur when smaller quantities are consumed
as part of a regular diet.
When xylitol is administered in an isolated form in bever-
ages, the xylitol molecules are no longer suciently absorbed
in the small intestine and will reach the colon. is concerns
other pentitols and all hexitols as well. erefore, con-
sumption of polyol-containing beverages—apart from those
based on erythritol—is not generally recommended. In the
colon, bacterial action converts -glucitol to low-molecular
T : Maximum bolus doses of some dietary sugar alcohols not
causing catharsis. Based on de Cock [].
Sugar alcohol
Maximum sugar alcohol dose
(g/kg body weight)
Male Female
Erythritol . .
Xylitol . .
.–..–.
-Glucitol . .
-Mannitol . .
Based on the -year Turku feeding study in adult subjects accustomed to
xylitol [].
decomposition products with much higher osmotic potential
than in the case of xylitol.
A form of adaptation to xylitol was rst discovered in
animal feeding studies and subsequently also in humans.
Most notably this phenomenon was discovered in the two-
year xylitol feeding study in Turku [, ]. is adjustment
hasnormallybeenlinkedtoanenzymeinduction;theactivity
levels of liver sorbitol dehydrogenase which catalyzes the ini-
tial oxidation of xylitol increase during habitual consumption
of xylitol.
e largest single boluses of sugar alcohols that can
elicit osmotic diarrhea in adult subjects dier based on
experimental details. Typical results obtained in feeding stud-
ies are shown in Table . Such values must not be regarded
as universally valid. e true eects depend on circum-
stances; evaluations conducted by dierent research teams
may not be exactly congruent.
Basedontheinterestfocusedondietsthatreduceintake
of poorly absorbed small-molecular-size carbohydrates, a
particular FODMAP concept was developed [, , –].
FODMAPs are short-chain carbohydrates that are poorly
absorbed in the small intestine. e term is an acronym
derived from “Fermentable Oligo-, Di-, Mono-Saccharides,
and Polyols.” e FODMAPs research and the low
FODMAPs diet concept was developed at the Monash Uni-
versity in Melbourne. It is important to emphasize the
role of polyols, such as xylitol, -glucitol, and -mannitol,
in the FODMAP group of carbohydrates. Understanding
the importance of dietary FODMAPs will be assisted by
comprehensive food composition data []. Although sugar
alcoholscanbeusedtoalleviatechronicconstipation,it
is thus obvious that sugar alcohols—with the exception
International Journal of Dentistry
of erythritol—should generally be avoided as part of low
FODMAPs diet. Dental health professionals are encouraged
to get familiar with the FODMAPs concept.
3. The Pivotal Role of
d-Glucitol and d-Mannitol
Older literature is cited here on purpose in order to emphasize
the existence of gradually growing clinical interest in this area
of research. One of the earliest scientic reports on the very
slow absorption rate of -glucitol was published by Dahlqvist
andTelenius[].Intractablediarrheaassociatedwiththeuse
of -glucitol has later been frequently reported in the clinical
literature. is has most oen resulted from the use of -
glucitol as a sweetener and bulking agent in dietetic candies
andchewinggum,althoughuseof-glucitolasavehiclefor
suspending active drugs for oral preparations can also cause
intractable diarrhea []. Only about  years ago several
researchers seemed surprised by the appearance of “dietetic
food diarrhea” caused by excessive -glucitol and -mannitol
consumption [] and by the metabolism of -glucitol by
gut bacteria [], even though already in the late s some
physicians had noted the very slow absorption of -glucitol
from the small intestine []. e situation was partly a result
of the limited information available in pediatric textbooks
concerning diarrhea caused by poorly absorbed osmotically
active substances. Pediatric gastroenterology texts contained
only passing references to this form of diarrhea, caused
by dietetic, -glucitol-containing candies or chewing gum
[, ]. A typical case report normally follows a series of
events similar to the following example: A -year-old boy
consumes six full packs of a -glucitol chewing gum brand.
e consumed amount of -glucitol is about  g. About
one hour aer the gum ingestion the child complains of
abdominal cramps and explosively passes about  mL of
thin liquid stool.
Several case reports began to call attention to -glucitol-
containing “diet foods.” Special “pink” diarrhea was caused
by -glucitol-containing vitamin C supplements; the pink
color was attributed to the cochineal dye added to the
preparation []. (“Cochineal” originally referred to the red
dye manufactured from the dried bodies of female cochineal
insects or wood lice; the dye can also be synthesized.) As
late as , physicians alerted public health experts to the
diarrheal potential of -glucitol [], as the quantities of
-glucitol used in the candy and food industry increased
signicantly.epopularuseof -glucitolincoughmixtures,
cough drops, and various pharmaceutical syrups also began
to receive attention; all of them have been reported as poten-
tial causes of diarrhea especially in infants. Such products
were, however, benecial from a dental standpoint, provided
that -glucitol replaced all fermentable carbohydrates pre-
viouslyusedinsuchproducts.iswasclearlyapositive
property of -glucitol-containing items.
It is well known that -glucitol and -mannitol are
present in a wide variety fruits and other plant material
[, ]. e concentration of -glucitol in dried fruit, such
as prunes, may reach levels that can contribute to diarrhea.
Anecdotal evidence suggests that, historically, pediatricians
advised mothers to give prunes to children with constipation.
Modern scientic research concerning the FODMAPs con-
cept has, however, more quantitatively underlined the role
of -glucitol and -mannitol in osmotic diarrhea and their
occurrence in natural products [, ] (vide supra).
As stated above, IBS was also reported to result from the
ingestion of mixtures of fructose and -glucitol []. Yao et al.
[] concluded that increased and discordant absorption of -
mannitol and -glucitol occurs in patients with IBS compared
to that in healthy controls. Both alditols induced gastroin-
testinal symptoms in patients with IBS independently of their
absorptive pathway, indicating that dietary restriction of the
alditols may be ecacious. Xiao et al. [] emphasized the
health-enhancing properties of so-called indigestible sugars
which include a large assembly of simple and complex dietary
carbohydrates including monosaccharides, oligosaccharides,
and certain alditols and disaccharide polyols. -Glucitol,
erythritol, and xylitol were presented as health-enhancing
substances. Similar comments have been made elsewhere
[, ], with evidence that particularly fructose conditions
the gut microora. “Toxicity” of -mannitol and -glucitol
wasdiscussedasearlyas[].RecentIBSpapersincluded
those of Shepherd et al. [], Tuck et al. [], Respondek et al.
[], Goebel-Stengel and M¨
onnikes [], and El-Salhy [].
Some researchers also interpreted other -glucitol eects
as positive: -glucitol therapy reportedly improved psycho-
motor performance in cirrhotic patients []. Patients with
hepatic encephalopathy improved in all ve mental func-
tion tests, whereas similar patients not receiving -glucitol
showed no improvement. -Glucitol has naturally been
exploited in medical practice as a cathartic preparation,
another useful sugar alcohol application. A comparison
between -glucitol and lactulose showed that both were
extensively fermented by the colonic ora []. It was sug-
gested that the much cheaper -glucitol could be used in
thetreatmentofpostsystemicencephalopathy.emedical
literature has, however, simultaneously been replete with case
reports and clinical studies relating detrimental -glucitol
eects, that is, intolerance to this sugar alcohol, as evidenced
by the literature references shown above. Based on eld expe-
rience and clinical evaluations, most experts contend that -
glucitol may produce osmotic diarrhea if ingested in amounts
of  g to  g. A debate on the possibility of glucose-stim-
ulated inux of -glucitol across the human jejunal mucosa
hascontinuedsincethelates[].
4. Also Disaccharide Sugar Alcohols May
Cause Osmotic Diarrhea
Maltitol (O-𝛼--glucopyranosyl-,--glucitol; molar mass
.) is a disaccharide sugar alcohol derived from maltose
by dehydrogenation. Owing to the hydrolytic cleavage of
maltitol by intestinal enzymes, free glucose and free -glu-
citol are formed. e liberated glucose molecules are
absorbed virtually completely, whereas the liberated -
glucitol is incompletely absorbed, contributes to osmotic
diarrhea, and is eventually subject to microbial fermentation
in the gut. Zun et al. [] showed already in  that
maltitolwillbedigestedandutilizedbyman,rat,andrabbit.A
International Journal of Dentistry
daily application of  g maltitol to humans “did not inuence
the parameters of well-being, compatibility, and fecal state.”
A study carried out with maltitol indicated that  g
maltitol in chocolate caused no signicant symptoms in
young adults, while  g caused mild borborygmus and atus,
but no laxation. An increased breath H2response indicated
primarily colonic maltitol fermentation []. Another study
reported that occasional or regular consumption of maltitol
was not associated with severe digestive symptoms [].
In both patterns of maltitol consumption, osmotic diarrhea
frequency was higher but appeared only for very high doses
of maltitol (about  g); maltitol did not lead to intestinal
ora adaptation aer a -day period of consumption. In
another experiment, a  g dose of maltitol caused transitory
osmotic diarrhea in  of  subjects (.%) []. e
symptoms could be suppressed by simultaneous ingestion of
partially hydrolyzed guar gum which consists of the ground
endosperm of guar (a legume) seeds. e gum, which swells
and disperses in water, contains a mannose- and galactose-
based polysaccharide, guaran.
It may be of interest that maltitol has been shown
to protect against dimethylhydrazine-induced tumours in
rat caecum and proximal colon. is may result from
butyric acid formation []. Another possible benet is
the maltitol-associated promotion of calcium absorption
and advantageous bone eects in rat models [, ], a
reaction that has also been observed with xylitol []. In
the past, some countries, including Canada, Australia, New
Zealand, Mexico, and Norway, have required manufacturers
to include warning labels on packages of maltitol-containing
comestibles, since “excessive consumption may have laxative
eects.” e FDA has regarded maltitol as a GRAS substance
(generally recognized as safe) with a warning about its cathar-
tic potential when consumed at levels above g per day (in
adults).
-Glucitol is also a hydrolysis product of isomalt (molar
mass .), which is an equimolar mixture of 𝛼--gly-
copyranosyl----glucitol and 𝛼--glucopyranosyl-,--
mannitol. e intact portion of isomalt and the unabsorbed
-glucitol and -mannitol molecules eventually reach the
lower parts of the gut where they serve as substrates for bac-
terial formation of volatile fatty acids. Isomalt may not be
consumed by adults in quantities larger than about  g per
day; atulence and diarrhea may occur. For children,  g per
day may represent a practical upper limit. Isomalt represents
those disaccharide sugar alcohols that are treated by the
human body as “dietary ber” and not as a regular disac-
charide. Consequently, isomalt can pass through the bowel
partlyundigested;partofitishydrolyzedinthesmallintes-
tine. Habitual consumption of isomalt may lead to partial
adaptation, which suggests decreased occurrence of gastroin-
testinal changes. Isomalt could be used as an alternative to
lactulose for colonic delivery system utilizing the principles
of a unique colon-specic delivery technique called CODES
[]. Since -glucitol has been associated with greater colonic
fermentation compared with isomalt [], its formation from
the latter should be considered.
Lactitol [-O-(𝛽--galactopyranosyl)--glucose; molar
mass .] passes through the small intestine almost
completely unabsorbed and is subject to microbial fermenta-
tion in the distal parts of the gut. Lactitol can cause atulence
and osmotic diarrhea in some individuals, since most subjects
lack the necessary 𝛽-galactosidase enzyme in the upper gas-
trointestinal tract. Aer reaching the large intestine, the lac-
titol molecules can pull water into the gut lumen by simple
osmosis. True loading tests with lactitol are limited. In a
human study, consumption of  g of lactitol per day resulted
in no gastrointestinal distress, while  g per day did cause
some changes []. Compare also with Natah et al. [],
whose study subjects reported no abdominal pain aer
ingesting lactitol.
In conclusion concerning disaccharide sugar alcohols,
excessive consumption of maltitol and isomalt can cause sig-
nicant osmotic diarrhea and atulence. True gastrointestinal
loading tests on lactitol should be repeated. e amount of
disaccharide polyols present in chewing gum is too low to
cause any gastrointestinal eects in most subjects.
5. Involvement of the Raffinose-Family
Galactooligosaccharides (GOSs)
e GOSs are not sugar alcohols but may occasion similar
gastrointestinal disturbances as the latter. Historically, the
GOS group of carbohydrates deserve attention in this con-
text because of the presence of GOS in some polyol-con-
taining manufactured foods. Indeed, eld experience sug-
gests that consumers frequently misjudge the causative food
agent when simultaneously consuming ranose-based food
of a leguminous nature and sugar alcohol-containing confec-
tionaries or medicines. erefore, the role of GOS will be
concisely discussed here. Legumes, rich in GOSs, normally
contain only insignicant quantities of sugar alcohols.
Oligosaccharides began to receive more attention as a
result of the growing interest in bringing new sources of
protein into the food system, including soybeans, which con-
tain these sugars. Oligosaccharides are not digested because
the human alimentary canal does not produce the necessary
enzyme, 𝛼-galactosidase. Nor are oligosaccharides resorbed
by the intestinal wall, owing to their high molecular weight.
Consequently, they come in contact with bacteria that inhabit
the lower parts of the intestine. e bacteria are able to uti-
lize the ranose-family oligosaccharides with subsequent
formation of atus []. ese oligosaccharides may also
promote the growth of bidobacteria in the human intestine
and cause diarrhea when consumed in excess of a particular
quantity [].
e molecular weight of oligosaccharides has an inu-
ence on atus formation. ese compounds include stachy-
ose (molar mass .), a tetraholoside, and verbascose
(., a pentaholoside). A holoside is a glycoside that
yields only glycoses on hydrolysis. Both have marked
eects as atus formers. Ranose (or melitose; .), a
triholoside, that is, O-𝛼--galactopyranosyl-()-O-𝛼--
glucopyranosyl-()-𝛽--fructofuanoside, normally has a
less signicant eect. e objective of emphasizing the role
of ordinary leguminous plants as a source of atus (and
diarrhea) is to underline the role of regular human food as
another common source of gastrointestinal discomfort.
International Journal of Dentistry
Flatulence is an old problem; the rst scientic reports
dealing with it were published early in the last century. Even a
slight increase in pressure in rectal gas may lead to symptoms
of discomfort. Researchers discovered about y years ago
that some GOSs play a part in atus formation. Flatus is oen
accompanied by a lowering of the pH. e lowered pH may
in turn aect the metabolism of other substances [, ].
Microbial fermentations of GOS in the large intestine
are responsible for atus components such as hydrogen,
methane, and carbon dioxide. Oxygen and nitrogen may also
be present and originate from swallowed air. Signicant, pos-
itive correlations were discovered between hydrogen produc-
tion and the following chemical components that are present
in various pea varieties: stachyose and ranose and various
glucans and pentosans. A study in patients with ileostomies
showed that % of ranose passed unabsorbed through the
small intestine; in the same study, % of -mannitol and
% of lactulose passed unabsorbed [–].
6. Main Features of Xylitol
Metabolism in Humans
Glucose and galactose which are common dietary carbo-
hydrates can be concentrated against a tenfold gradient
by an active transport mechanism that assures their early
absorption in the intestinal tract [, , , , , ]. e
question is of a facilitated transport mechanism. In the case
of xylitol and -glucitol, however, there is no evidence of
such transport mechanisms [, –]. As mentioned above,
their absorption takes place based on free diusion, or, if
an active transport system exists, it has only a low anity.
e driving force behind free diusion is the concentration
dierence for the substance in question [–]. Another
factor limiting diusion is the pore size []. e diameter of
hydrophilic pores may range considerably from less than one
nanometer to between . nm and .nm, but the structures
may not assume the shape of pores but, rather, tunnel-like
channels. Although the molecular weights of xylitol (.)
and -glucitol (.) dier by only about %, this dierence
is signicant in the borderline range of free diusion. e
symmetrical conguration of the xylitol molecule may facil-
itate a single-le diusion of the molecule through tunnels.
e greatest portion of absorbed xylitol is metabolized
in the liver, although kidneys and other tissues are also sites
of xylitol metabolism [, ]. Red blood cells metabolize
xylitol readily. Most xylitol is metabolized by a pathway
involving normal, physiologic enzyme-catalyzed steps of the
pentose phosphate pathway. is pathway is a portion of
the glucuronate-xylulose cycle, also called Touster’s cycle
that was introduced already in the s and s [, –
]. It has been dicult to visualize in practical terms the
link between this cycle and the better-known glycolysis. It is
possible that the German researcher B¨
assler [] succeeded
in outlining this link graphically (Figure ). e identity of
the enzymes involved in this cycle and theoverall metabolism
of xylitol in human tissues was established by the mid-s,
when the United States FDA released its expert opinion on
the safety of xylitol and lactose. is resolution (vide infra)
isstillineectandformsthebasisfortheFDAsmost
Dietary xylitol Xylulose 5-phosphate
Glucose
Glycolysis
Glucose
6-phosphate
Glucuronate-
xylulose cycle
Lactic acid
acid
Pyruvic
CoA
Pentose phosphate shunt
Several intermediates
F : Relationship between the metabolism of xylitol and
glycolysis in humans. e scheme describes the metabolism of
dietary xylitol in broad outline only. e body receives energy
from glycolysis (the thick horizontal arrow). e rst intermediate
of glycolysis is glucose -phosphate which forms an important
link between glycolysis and another metabolic pathway, called
the pentose phosphate shunt, or pentose phosphate cycle (curved
arrow). e thinner black arrow represents the glucuronate-xylulose
cycle of Touster. e dierences in the thickness of the arrows
reect the relative portion of these three pathways in the overall
metabolism. Although the signicance of the Touster cycle is minor
from the energetic point of view, it is nevertheless absolutely
necessary for body functions. Pyruvic acid which may be regarded
as the end product of glycolysis can be further metabolized in two
ways: reduction to lactic acid under conditions of limited oxygen
supply, or becoming a part of coenzyme A when the oxygen supply
is sucient. e scheme shows how xylitol can contribute to the
overall energy metabolism of the body. e original scheme of
B¨
assler [] was modied and completed by the present author.
recent safety statements regarding xylitol and also for the
scientic opinion of the Joint Expert Committee of the World
Health Organization (WHO) and the Food and Agriculture
Organisation (JECFA) resolutions concerning the safety of
xylitol.
7. True Loading Tests of Xylitol in Humans:
A Historical Perspective
Few research papers have reported on gastrointestinal
changes during xylitol consumption. is partly results from
the nonexistence of such changes in clinical trials aimed at
investigating oral biologic and dental eects of xylitol. In
most stomatologic studies, xylitol consumption levels have
been relatively small, and, consequently, the researchers did
not need to focus on possible side eects of xylitol consump-
tion. e scantiness of such reports is unfortunate, since the
next generation of consumers, health-care authorities, and
medical and dental practitioners has retroactively started to
ask for hard data on the relationship between the consump-
tion of xylitol and bowel movements, atulence, meteorism,
and other bowel reactions.
International Journal of Dentistry
Observations on the occurrence of diarrhea in studies
involving consumption of xylitol and other dietary alditols
will be reviewed below, as reported by the authors of those
studies. e individual studies are summarized instead of
showing study details in the form of tables. is results
from the publication of several early studies in dicult-to-
locate journals, which have not provided abstracts of papers.
Since these studies represent real-life situations, their review
enables present readers to obtain direct information on the
studies involved, with practical instructions regarding dosage
levels of alditols for patient counselling purposes.
By the mid-s, various medical and dental benets
of xylitol were already known. Considerable experience had
become available since the s from the former Soviet
Union, where the metabolism and uses of xylitol for nutritive
andmedicalpurposeshadbecomeafavoredresearchtopic.
e Soviet researchers were not aware of the dental eects
of xylitol until the publication of the Finnish Turku Sugar
Studies in  []. is study prompted Galiullin [] to
undertakeatwo-yearxylitoltrialinthestateofKazan.His
resultswereinlinewiththoseoftheTurkustudy(vide infra).
Some Russian-language medical articles have been dicult to
access, but a valuable contribution to this xylitol literature was
made by Dr. Nesterin from the Moscow Nutrition Institute.
He wrote a comprehensive historic review of the Soviet
investigations into the general medical eects of xylitol,
including its toxicity, inuence on bodily functions in diabetes
mellitus, disorders of the hepatobiliary system, and other
medical conditions. is Russian-language article was trans-
latedintoEnglishandappearedininaGermanscientic
journal []. Although the article focused on diabetes and
disturbances of the liver and gallbladder system, observations
on gastrointestinal eects of xylitol were also made. Nesterin
also described a large number of animal experiments. e
direct quotes below are examples from the translation.
Nesterins review showed that the Soviet medical authori-
ties recommended xylitol in the treatment of various medical
conditions. Gastroenterological statements indicated that
“good tolerance to xylitol was noted in the treatment of
children who received – g xylitol for  weeks.” Similar
conclusions were made aer diabetic children had received
 g of xylitol daily for one month. In a study carried out
at the USSR Academy of Sciences Central Hospital,  adult
diabetic patients received – g of xylitol daily for one
year. e researchers noted no side eects; “laxative eects
never occurred,” while disorders of carbohydrate metabolism
disappeared “and the patients felt better.” As a result of
these observations, Soviet physicians started to prescribe
xylitol to patients suering from constipation. A common
dosewasgofxylitolwhichwas“consumedwell;no
pathological symptoms occurred, while the bolus structure
normalized (without diarrhoea).” e Soviet researches also
stated that female patients, aged  to  years, and who
had liver and gallbladder problems, beneted from a -
week xylitol program ( g per day); dispepsia [sic]and
painfulness during palpation vanished.” “Side-eects—such
as meteorism and watery stools—occurred seldom” [].
In the mid-s, the present author received a personal
report from Dr. M. V. Milishnikova who then worked at the
Department of Propedeutics of Internal Diseases of Astra-
chan Medical Institute. Her report represented an account
of medical studies entitled “Xylite in Ration of Patients with
Diabetes Mellitus”[sic].Relatedtoosmoticdiarrhea,the
followingisanexcerpt,indirectquotation,fromthereport:
“Twenty-one - to -year-old diabetic patients received
gofxylitolinmLofwaterperdaybeforeameal.
No side eects were observed.” e study focused on the
glycemic curve and on the extent of glycosuria, both of
which remained within the normal physiologic range. Dr.
Milishnikova further stated that “administration of xylitol
improved these patients’ feeling, and had a favorable eect on
bile secretion and emptying of intestine” [sic]. Her patients
also included diabetic subjects who had frequent pain in
the right hypochondrium and suered from constipation.
Following the “xylite treatment ( g daily), these symptoms
disappeared.” She added, however, that the improvement in
carbohydrate metabolism was not observed in all patients.
It is also possible that the patients’ meals contained water-
absorbent dietary bers which may have alleviated gastroin-
testinal responses.
In another experiment - to -year-old diabetic patients
received  g of xylitol divided into  or  portions during one
day.“Nosideeectssuchasepigastricpain,nausea,vomiting,
and diarrhoea were observed.” e metabolic parameters
werenormal(afavorableinuenceonbilesecretionwas
noted). In other experiments a general improvement in the
diabeticstateofalargenumberofdiabeticsubjectswas
observed. An expected observation was the relief of constipa-
tion some subjects suered. e Soviet physicians concluded
that “xylite can be used in diet for patients with diabetes
mellitus.” Some of these results were published in Russian
already in  by I. V. Domareva (in Vop r. P itan ija,No.
, p. ) and in the same year by M. S. Marshak and I.
S. Savoshtshenko (in Med. Gazeta,No.),asreportedby
Milishnikova.
Coinciding with the publication of the above Soviet
experiences in the German medical journal, several research
groups in Germany got engrossed in detailed gastrointesti-
nal studies with xylitol. Research teams in other countries
followed suit. e following twenty reports provide quanti-
tative information on osmotic diarrhea associated with the
consumption of xylitol by human subjects.
(1) ree-Week Feeding Study. Dubach et al. [] tested a group
of  subjects of both sexes, aged – years. e subjects
were given xylitol for  days in the form of “compressed
material” and in jam, increasing the doses up to a maxi-
mumofgperday.Intolerancewasnotobserved.Aer
onemonththesubjectsreceivedgxylitolinonesingle
dose without any signs of intolerance. is dose could be
increased to a maximum of  g/day. At this level, aversion
to sweets was noted. Body weight, fasting blood sugar values,
and stool consistency remained uninuenced. Diarrhea rst
developed at  g/day, but, according to the authors, this
resulted mainly from poor distribution of single doses. In
another experiment, tolerance for xylitol and -glucitol was
compared to levels of up to  g per day for up to two
weeks. Twenty-one subjects out of  preferred xylitol over
International Journal of Dentistry
-glucitol; meteorism and atus were more common with -
glucitol at the same dose. e authors concluded that “there
were no signicant adverse eects with xylitol except for
loose stools which could be controlled by appropriate dosing
schedule.
(2) Eect of Increasing Dosage. Asano et al. [] demonstrated
by modern absorptive gastroenterological techniques that,
in adult men, xylitol absorption decreases with increasing
dosage, being % absorbed at  g in a single dose, % at  g,
and % at  g xylitol in a single dose. Up to  g of xylitol
wasfound“tobewellabsorbedbyhumansubjectsandtohave
no adverse eect judging laboratory tests and symptoms.”
Asano et al., therefore, showed no incidences of laxation in
dosinghisadultsubjectsatalevelofgofxylitolasasingle
bolus. e authors concluded that -glucitol at a single dose
of only – g leads to diarrhea in young subjects whereas
approximately twice this quantity of xylitol (– g) would
berequiredforasimilareect[].F
¨
orster [] reevaluated
these studies in detail.
(3) Eect of 120 g Doses. Amador and Eisenstein adapted ve
persons with increments of  g of xylitol per day in three
individual doses at three-day intervals up to g per day.
e authors concluded that, overall, there was “virtually no
gastrointestinal stress at less than  g/day.” It should be noted
that the subjects who showed diarrhea at  g per day weighed
only about  kg and that the tolerance was greater than  g
to  g of xylitol per day for an adult,  g being the highest
level tested with adaptation. is study was described in detail
by Brin and Miller in  [].
(4) Two-Year Feeding Trial. A long-term feeding trial on
xylitol was carried out in – in Turku, Finland [, ].
ree groups of volunteers, totalling , lived for two years
on strict diets so that comparisons could be made with regard
to the sweeteners tested: sucrose (S), fructose (F), and xylitol
(X). ese diets were given to the subjects free of charge from
the institute carrying out the research. A total of about twelve
food manufacturing enterprises participated in providing a
wide variety of food items for the subjects [, ]. is
study constitutes perhaps the most compelling and detailed
evidence so far on the eects of long-term uninterrupted
consumption of a sugar alcohol in humans in a situation
where the average daily quantities of the substance amounted
to about  g per day. Consequently, since this study remains
theonlylong-termtruefeedingtrialwithanysugaralcohol
conducted in humans and since the above publication (a
 supplement to Acta Odontologica Scandinavica)has
not been readily available, this research is summarized
below.
esizesofthetestgroupswereS,;F,;X,.e
average daily amount of the sweeteners consumed in a varied
assortmentoffoodwasS,g;F,g;X,g.(ecalculated
consumption value for sucrose was most likely somewhat
higher, since subjects were known to consume food obtained
from other sources.) In this study, the highest daily doses
of xylitol were  to  g. e subjects were continuously
monitored by medical research teams. e study showed that
020 40 60 80 100 120 140
Days
0
2
4
6
8
10
12
14
16
18
Number of subjects
F : Gradual lessening of osmotic diarrhea and atulence
in human subjects who consumed on the average  g of xylitol
daily for two years. e results are here shown for the rst -day
period. e ordinate gives the number of subjects complaining even
about slight diarrhea or increased defecation frequency on each test
day. e initial peaks of consumption were found to result from
the interest of the subjects to get acquainted with the new dietary
regimen. Modied from [].
the consumption of xylitol and fructose was associated with
osmotic diarrhea, atulence, and gastric distress.
e ability of xylitol to produce gastrointestinal distur-
bances was found to depend on individual physiological
responses in each volunteer. In many cases, subjects reported
no symptoms even though high amounts of xylitol were
consumed. All pregnancies and deliveries in the xylitol group
were normal. e overview of the trial [] concluded that
“the osmotic diarrhea that occurred in a number of subjects
aer heavy peroral xylitol loading gradually disappeared as
a phenomenon of adaptation took place” (Figure ). e
illustration shows the number of subjects who reported loose
stools during the rst  days of the trial. As expected, sev-
eral subjects experienced loose stools during the rst weeks.
Aer the rst  days, the frequency of symptoms continued
almost unchanged for the rest of the study. Consequently,
during the last  days of the feeding trial, the occurrence of
diarrhea in the xylitol group was nearly of the same frequency
asinthesucroseandfructosegroups;thatis,thereportsabout
diarrhea decreased to about one-quarter compared to the rst
weeks. e total number of intakes of xylitol-containing food
items was , over the course of the two-year trial, or
aboutreportedintakesofxylitolfoodpersubjectand
per month. A total of  subjects in the xylitol group were
considered as having consumed exceptionally high quantities
of xylitol. Within this -subject group, the overall number of
days with an intake of – g of xylitol was , over two
years. In these subgroups, the overall numbers of days with an
intake of – g and > g were  and , respectively.
Aer the adaptation phase of about three weeks, it was
noted that several subjects had not reported diarrhea-like
conditions even though they were deliberately attempting to
cause laxative eects by consuming  g of granulated xylitol
asasingledose.Outoftheinitialnumberofsubjects()who
International Journal of Dentistry
started the xylitol regimen, ve discontinued the program as
aresultofstudyfatigue(subjects),poorcompliance(one
subject), employment reasons (one subject), and reported
persistent diarrhea (one subject). e nal medical reports
(including gastrointestinal information) were thus available
from  xylitol-consuming subjects. is information was
obtained by means of written diaries and was considered
somewhat subjective. It is possible that the levelling o
of the regression curve in Figure  resulted in part from
subjects gradually learning to use xylitol food in moderation.
However, a true adaptation in the intestinal ora and liver
wasmostlikelyalsoinvolved.eresearchersconcludedthat
“xylitol was well tolerated by the majority of the subjects.”
(5) Two-Year Soviet Union Study. As mentioned above,
following the completion of the Turku Sugar Studies [,
], the rst conrmatory clinical evidence of the caries-
limiting qualities of xylitol was obtained from the study
publishedinbyGaliullin[].Inthistwo-yeartrial,
- to -year-old subjects received  g of xylitol daily in
the form of candies. e comparison group received  g of
sucrose in the form of similar candies. e objective was to
replaceone-halfofdailyconsumptionofsweetsinthexylitol
group. In addition to registering of dental caries outcomes
(which showed xylitol to reduce caries incidence by about
% compared with sucrose), the study investigated several
anthropometric, pulmonary, otolaryngeal, rheumatologic,
endocrinologic, and metabolic parameters of the subjects.
e children’s comprehensive physical check-ups revealed no
dierences between the xylitol and the control groups, apart
from signicantly lower caries incidence in the former. e
groups also did not dier with regard to bowel movement
recordings.
(6) University of Texas Study. Astudyentitled“OralXylitol
in Humans” was published by Wang et al. []. e study
was carried out at the University of Texas System Cancer
Center in Houston. Seventeen adult subjects of both sexes
received xylitol enterally so that the xylitol level was gradually
increased from  × g per day to × g per day over a
-day period, with the nal dose maintained for  days. e
study investigated a total of  clinical-chemical parameters.
Severe diarrhea was observed in one male subject when
the xylitol dose was  × g per day. Milder diarrhea and
atulence were reported in all subjects. Adaptation to xylitol
was observed. e authors concluded that “the adult human
can tolerate substantial amounts of daily xylitol.”
(7) Reexamination of the Turku Sugar Study Subjects. e
general health of the participants in the above-mentioned
Turku Sugar Studies [, ] was reexamined four years fol-
lowing the nal xylitol feeding [, ]. ese reexaminations
included a special comparison of metabolic tolerance test of
nine “xylitol chronics,” that is, human volunteers who had
used xylitol regularly for .–. years (the rst two years in
the capacity of participants in the original two-year feeding
trial). In this tolerance test, the subjects consumed, over 
days, – g of sucrose per day with the basal diet (as in
the case of the study of F¨
orster et al.; vide infra), followed by
the consumption of – g of xylitol per day in the basal
diet for  days, and similar consumption of xylitol in normal
diet for  days. is basal diet (formula diet) did not contain
ber and thus lacked the water-binding capacity of normal
food. e subjects were investigated using versatile clinical,
anthropometric, ophthalmological, and metabolic tests. e
xylitol loading tests were not found to result in any abnormal
metabolic reactions. As expected, the sudden increase in
the level of xylitol consumption from those to which the
subjects were accustomed resulted in osmotic diarrhea in
some subjects. ese symptoms disappeared in most cases in
todays.Nosignicantdiarrheawasreportedbysubjects
who consumed normal diet plus xylitol. Four instances of
diarrhea(intwosubjects)andsixinstancesofatus(in
three subjects) were recorded during the basal sucrose diet
and normal diet periods (without xylitol). Upon completing
this review, all nine “xylitol chronics” are alive, the oldest
ones being nearly eighty years old. Four of them have
continued uninterrupted daily consumption of xylitol over 
years.
(8) 55-Day Study in Children.˚
Akerblom et al. [] studied
the tolerance of increasing amounts of dietary xylitol in
healthychildrenagedyears.Xylitolwasincorporated
into the diet in the form of chocolate, chewing gum, wafers,
crystallinexylitol,meringuecandies,yoghurt,andicecream.
e daily dose was increased from  to , , , and  g
(in successive -day increments) and nally decreased to
 g for  days. Gastrointestinal side eects were recorded
dailyduringthe-dayxylitolconsumption,aswellasduring
xylitol-free periods before and aer the trial. Flatulence was
the most common side eect occurring infrequently in about
half of the subjects during the  g/day intake of xylitol
andinthemajorityofthechildrenathigherdoses.During
the latter periods of high-level xylitol administration, an
obvious adaptation to the substance was observed. Transient
diarrhea (but no increase in the number of stools) occurred
in four children at g/day xylitol consumption and in one
childatg/day.eauthorsconcludedthat“areasonable
consumption of xylitol in the form of chewing gums and
small candies or confections is harmless for children, and
can be recommended when this would replace consumption
of similar confections sweetened with sucrose or other
cariogenic sweeteners.”
(9) German Study in Healthy Adults. F¨
orster et al. []
carried out a study on  healthy volunteers who consumed
a standardized basal diet consecutively supplemented with
either sucrose ( days, – g/day) or xylitol ( days, –
 g/day). With the exception of a few cases of diarrhea only
at the start of the xylitol regimen, no other clinical signs
indicated treatment-related side eects. is nding was
considered remarkable, since the liquid nature of the formula
diet consumed is devoid of ber (and hence lacks water-
binding capacity) and the subjects investigated had not been
previously exposed to xylitol. (In the previous xylitol loading
test of a similar nature [, ], subjects were partially adapted
to xylitol.) e subjects were allowed to reduce somewhat
the xylitol dosage until diarrhea subsided, although, in cases
 International Journal of Dentistry
where diarrhea occurred or persisted, the achieved levels
of xylitol nevertheless corresponded approximately to the
targeted level of up to g/day. “is provided further evi-
dence that the gastrointestinal tolerance of the subjects was
good” [].
In an earlier paper, F¨
orster [] referred to older German
experiments which indicated that xylitol was well tolerated by
children and diabetic subjects. For example, in a study carried
out by Mellingho already in  (published in ), xylitol
was used as a substitute for sugar with diabetics. Using low
dosages ( g per day), there were no symptoms of diarrhea.
Only at higher dosages ( g in tea), did cases of diarrhea
occur. In another experiment of his own, F¨
orster found that
 g of xylitol was tolerated “without much diculty” by six
volunteers over a period of ten days []. F¨
orster found no
adverse gastrointestinal eects during administration of  g
of xylitol over a period of four weeks to diabetic children.
F¨
orster mentions in his paper also a study by Mertz et al., who
observed no symptoms aer their subjects had consumed
 g xylitol, and a study with diabetic children who received
gxylitolperdayoveraperiodoffourweeks.Onlyonechild
withdrew prematurely from the sequence of experiments on
accountofdiarrhea[].
(10) Chronic Xylitol Users. Diarrhea-associated data of 
subjects,whohadhabituallyusedxylitolfor.to.years,
was published in  []. Four of the subjects had also
participated in the above-mentioned xylitol loading test [].
e group of  included three children who had used xylitol
formostoftheirlives.eiragesatthecommencementof
the program were ., ., and . years. Six adult subjects in
this group had also participated in the two-year Turku Sugar
Studies (–) involving, on the average,  g intake
of xylitol per day in the form of versatile xylitol products
[,,,].Followingtheterminationofthefeeding
study, that is, during the next . years, the six subjects
consumed xylitol daily mostly in the form of chewing gum,
troches, and chocolate, at consumption levels ranging from
. kg per year to  kg per year. Two additional adults in
the -subject group had used a total of  kg and .kg
of xylitol, respectively, during –, and . kg and
 kg, respectively, over the next . years (the .-year gures
resulted mostly from the use of confectioneries). Detailed
paper diary and questionnaire performances showed that
none of the subjects reported diarrhea during the entire study
period (the children’s data were based on parental monitor-
ing). Absence of gastrointestinal disturbances in the two
youngest children was noticeable. eir average daily fre-
quency of xylitol intake varied from  to  during their .-
or .-year participation.
(11) Eect on Gastric Inhibitory Polypeptide.egroupof
Salminen[]studiedsixhealthyvolunteers,agedyears,
whowereunaccustomedtoxylitol.esubjectsreceiveda
single  g xylitol dose in  mL water aer a  h fast. Two
subjects experienced transient diarrhea and one complained
of atulence. An important observation was that this xylitol
administration had no eect on the concentration of gastric
inhibitory polypeptide or insulin in plasma. In another study,
an aqueous solution of xylitol ( g/ mL) was used to study
gastric emptying (to wash down a scrambled-egg meal).
Aer ingestion of xylitol, gastric emptying was markedly
prolonged. Xylitol decreased food intake, causing the authors
to suggest a role for xylitol as a potentially important agent in
dietary control []. Salminen et al. stated in a later study []
that two of six healthy - to -year-old volunteers reported
sudden transient diarrhea - h aer xylitol consumption and
that all six had soer stools and increased stool frequency
aer xylitol intake. In this case the subjects received a  mL
drink containing  g xylitol or  g glucose.
(12) WHO Study. In a collaborative Hungarian World Health
Organization xylitol eld study carried out during early
s, institutionalized - to -year-old hearing- and sight-
impaired children or orphans (𝑛 = 278)receivedg
of xylitol daily over a period of three years. During the
entire course of the study, no problems were encountered
with regard to the reported frequency of laxation or possibly
associated abdominal discomfort [].
(13) Oral Xylitol in American Adults. Twelve healthy adult
subjects were given xylitol in incrementally increasing daily
doses from  g in three doses to  g in two doses along
with a regulated diet []. All subjects experienced dose-
dependent diarrhea. One of the subjects was intolerant of
doses greater than  g, while  subjects tolerated daily doses
of up to  g. Adaptation was observed in most subjects.
e authors concluded that “oral xylitol in combination
with normal American diet imposes no side eects other
than gastrointestinal intolerance as those observed in West
Germany and Scandinavian countries.”
(14) Metabolic Responses to Xylitol and Lactitol. Eight healthy,
nonobese male subjects with a mean age of 25 ± 1 years
werestudiedaertohfast.esubjectsingested,in
 mL water, either  g glucose,  g xylitol, or . g lacti-
tol monohydrate within - min. None of the subjects had
abdominalpainordiarrheaduringthestudy[].
(15) Seattle Studies.LamsgroupattheUniversityofWash-
ington used xylitol-containing foods in xylitol feeding studies
in young children aged  to  years []. e foods included
popsicles, puddings, gum drops, gelatin dessert, cookies,
and popcorn. is experiment was not a loading test but
measured children’s acceptance of xylitol-based foods; the
amount of xylitol presented to the children on a tray of xylitol
foods was up to . g per episode. ese snack foods were
generally well tolerated by children. In another experiment
xylitol-containing milk was well accepted by - to -year-old
children [].
(16) South Korea Study. In a kindergarten study carried out
in South Korea in -,  -year-old children were
divided into three groups of equal size. Two of the groups
received, in the form of chewing gum, . to . g of xylitol
or -glucitol, respectively, daily for six months, with one
group serving as a comparison []. None of the subjects
had gastrointestinal problems, as reported by kindergarten
International Journal of Dentistry 
personnel and parents. e children regarded the use of
chewing gum as a pleasurable experience.
(17) Comparison between Erythritol and Xylitol. Sixty-four
adult subjects completed a study where the gastrointestinal
responses to single oral bolus doses of erythritol and xylitol
(, , or  g) were investigated []. ese subjects can be
regarded as unaccustomed to the polyols tested. Compared
with a  g sucrose dose,  g xylitol in water signicantly
increased the number of subjects reporting nausea, bloating,
borborygmus, colic, watery feces, and total bowel movement
frequency. e  g xylitol dose increased bowel movement
frequency of passing watery feces, while  g erythritol sig-
nicantly increased the number of subjects reporting nausea
and borborygmus. Lower doses of  and  g erythritol did
notprovokeasignicantincreaseingastrointestinalsymp-
toms.
(18) Infant Study. Six- to -month-old infants received xylitol
in  g doses thrice per day or . g once a day in the form of
an aqueous solution for three months (to assess the eect of
xylitol on otitis media). A % -glucitol solution was used as a
control. Gastrointestinal complaints, excessive gas, diarrhea,
and vomiting were monitored. e authors reported that “the
infants tolerated the oral xylitol solution well” [].
(19) Japanese Study in Adult Subjects. e noneective dosage
of three sugar alcohols not causing transitory diarrhea was
investigated in  male and  female subjects in a Japanese
study []. e test substances ( to  g/ mL water) were
consumed - h aer meal. e noneective dose level of
xylitol was . g/kg body weight for males and . g for
females. e corresponding values for lactitol were about %
to % smaller, while erythritol was better tolerated: . g/kg
body weight for males and . g/kg for females.
(20) Japanese Study in Preschoolers.Xylitolchewinggumwas
given to --year-old preschoolers in a Japanese study [].
is study was chosen for the present piece to represent
another attempt at monitoring the occurrence of gastroin-
testinal side eects in a regular chewing gum study in young
children. e authors managed to monitor the occurrence
of osmotic diarrhea in the children with the aid of parental
participation. e children were supposed to chew one gum
pellet  times/day for  months, that is,  × (approximate
number of test days) =  pellets in toto.erequireddaily
consumption of xylitol was planned to amount to . g per
day. e percentage of the children who experienced diarrhea
during the xylitol consumption period was % ( subjects
out of ). Interestingly, % of children ( out of ) who
did not consume xylitol gum “well” (i.e., their cumulative
gum consumption was fewer than  pieces in  months)
experienced diarrhea, a proportion larger than among the
“well-consumed” children (%).
8. General Conclusions on Loading Studies
with Xylitol
Following the clinical and laboratory xylitol studies in
humans and experimental animals completed by the
mid-s, the FDA commissioned the Life Sciences
Research Oce (LSRO) of the Federation of American Soci-
eties for Experimental Biology (FASEB) to review and eva-
luate the available biomedical information on sugar alcohols
and lactose. FASEB and LSRO provide scientic assessments
of topics in the biomedical sciences. Reports are based on
comprehensive literature reviews and the scientic opinions
of knowledgeable investigators engaged in work in relevant
areas of biology and medicine. Health-care authorities
around the world frequently base their opinions on these
regulatory and scientic bodies of the United States, that
is,FDA,FASEB,andLSRO.Inclusionoflactoseinthesci-
entic survey of sugar alcohol research can be regarded as a
wise tactical decision. Aer the publication in  of the nal
scientic opinion, entitled “Health Aspects of Sugar Alcohols
and Lactose” [], there has been no need to examine the
safety of xylitol and lactose further. Authorities in various
countries have, when necessary, referred to this FDA resolu-
tion. New information regarding the absorption and meta-
bolism of xylitol and other sugar alcohols has become
available aer the publication of the joint FDA-LSRO
resolution. e new information,some of which was detailed
in cases ()–() above, has conrmed the historic knowledge
[]andisincongruencewiththeFDA-LSROresolution
regarding the occurrence of gastrointestinal eects associated
with the consumption of xylitol and other sugar alcohols.
Ten years aer the above joint FDA-LSRO resolution, the
FDA announced its “Final Rule” regarding the use of sugar
alcohols in the nonpromotion of dental caries, referring to
the GRAS-listed status of xylitol []. By the mid-s,
the advent of erythritol as a dietary sweetener had not yet
occurred.
Gastrointestinal side eects normally occur aer con-
sumption of excessive doses of slowly absorbed carbohydrates
such as lactose and sugar alcohols (apart from erythritol). e
severity of symptoms depends on the individual consumer,
state of fasting, dose consumed, mode of ingestion, molec-
ular characteristics of the test substance, composition and
structure of the other food simultaneously consumed, and
existence of any prior period of adaptation []. Protection
of the consumer from polyol-induced diarrhea can best
be achieved by providing appropriate instructions on food
label. Accordingly, the Scientic Committee for Foods (SCF)
of the European Economic Community (EEC) emphasized
already in the late s that ingestion of  g -mannitol
andg-glucitoldailyintheformofcommercialfood
products must bear a warning statement indicating that
“excess consumption may have a laxative eect.” At that
time no corresponding requirement was formulated by EEC-
SCF for xylitol, since the general understanding was that
xylitol consumption does not normally cause gastrointestinal
problems when xylitol is used “for dental purposes, even
by diabetic subjects.” Such formulations are now available
bytheEuropeanUnion(EU),however,butonlyconcerning
authorized EU dental health claims, and not specically
regarding diarrhea []. Osmotic diarrhea was touched upon
only by stating that “there is a risk of osmotic diarrhea at
excessive intakes of polyols. Children younger than  years
should not use chewing gum (owing to choking hazard).”
 International Journal of Dentistry
e absoluteness of the above-mentioned age limit is
understandable in view of the composition of SCF and
because relatively few studies in infants have been carried
out explicitly from the point of view of gastrointestinal
polyol eects. Most likely, some of the SCF members lacked
personal, long-term in-family experience in the use of xyl-
itol. Long-term eld experience obtained especially within
Finnish families, kindergartens, and day-care centers strongly
points to the role of families and public institutions in
teaching children to use xylitol chewing gum properly as part
of lunch programs and oral hygiene practices. Accordingly, a
largenumberof-and-year-oldFinnishchildrenhavecus-
tomarily received xylitol products under parental guidance.
Virtually all energy for the uptake of xylitol from the
intestinal lumen is oered by the concentration gradient [].
If the absorption capacity of xylitol is exceeded, osmotically
induced diarrhea may occur. It has been dicult to deter-
mine the proportion of orally administered xylitol that is
absorbed from the intestinal lumen in each particular set of
circumstances. is portion seems to depend, among other
things, on whether direct oral intake or consumption in
combination with solids is involved. It has nevertheless been
established that even when consumed in the most direct
form in solution, a signicant portion of xylitol will be
absorbed, since the associated metabolic eects can only be
interpreted in this way [, ]. e single dosage of xylitol that
is normally tolerated without diarrhea by healthy humans
ranges from  g to  g, although considerable variation
mayoccurbetweenindividuals[,,].Someadultscan
probably tolerate up to more than  g xylitol daily, provided
the dosage is increased gradually and that such quantities are
consumed during the entire day and not as a single bolus
[]. In general, aer adaptation, adults will tolerate – g
of xylitol daily without great diculty [, , ].
Itisnecessarytorecallthat,for“dentalpurposes”(i.e.,for
caries limitation), it may not be necessary to consume more
than – g of xylitol daily, provided that this dose is taken
in several smaller portions; protection against caries is more
eective when xylitol is used in several smaller quantities
during the day [, , ]. Success in caries prevention by
xylitol also relies on general oral hygiene and dietary prac-
tices; xylitol may not compensate for serious neglect of oral
hygiene. e previously recommended to  g daily doses of
xylitol for caries prevention were based on early xylitol trials.
Since some researchers have tested even smaller daily doses,
employing caries-resistant study cohorts, too-short interven-
tion periods, simultaneous use of uoride, and other pro-
cedures that have unnecessarily impoverished the intended
xylitol program, this author now recommends  to g
daily xylitol doses for caries prevention. In case of rampant
caries and poor oral hygiene, the doses may be even larger.
Naturally, several other precautionary steps must also be
taken when planning a xylitol-based caries program [].
e current concept of xylitol as a safe dietary food
ingredient is largely based on the above metabolic follow-up
and loading tests [, –] carried out in connection with
the Turku Sugar Studies [, ] and on the “defensive animal
experiments” that led to a joint FDA-FASEB-LSRO release
on the safety of xylitol []. ese safety aspects include
gastrointestinal eects of xylitol, such as its slow absorption
and potential causing of osmotic diarrhea in situations where
recommended upper consumption limits are exceeded by
unaccustomed subjects.
Tolerance to xylitol is better when it is consumed as part
of regular meals or snacks. Even when consumed in confec-
tionery items, such as pastilles, troches, lozenges, chocolate,
and chewing gum, the risk of osmotic diarrhea is not remark-
able,sincethoseitemsarenormallyusedinsmalleramounts.
Xylitol present in beverages normally causes diarrhea at
lower xylitol levels than when present in solid items (this
also applies to -glucitol). Experience from the Turku Sugar
Studies [, ] suggests that it may not be advisable to use
xylitol as a sweetener in so drinks. Since use of coee and
tea is normally self-restricting, it is possible to use xylitol as
a sweetener in coee and tea without notable gastrointestinal
symptoms. Simultaneous consumption of ber-rich food will
lessen the ability of xylitol to cause osmotic diarrhea. Such
bers include cellulose and xylans (a group of so-called hemi-
celluloses) which impute water-holding properties, resulting
in considerable bulking of digesta. Cereals, among other
plant-derived foods, are rich in xylans.
Long-term eld experience has shown that even health-
conscious consumers may be unable to dierentiate between
mild gastrointestinal eects occasioned by such common
dietary items as legumes, lactose, and -glucitol, if these
are consumed together with xylitol. Furthermore, several
xylitol-containing confectionery items also contain glucose
syrups and maltose syrups or polydextrose—popular bulking
agents and sugar replacers which are slowly absorbed and
may cause similar eects as polyols. Although polydextrose
has been claimed to provide physiological eects similar to
those of other bers and to be better tolerated than most
other low digestible carb ohydrates (such as p olyols), excessive
consumption of polydextrose can lead to osmotic diarrhea
[]. Finally, it may always be justiable to contemplate the
possibility that humans may to a certain extent have addled
our nutrition by continuous introduction of partly or fully
synthetic food ingredients to replace the traditional ones that
have constituted our evolutionary environment.
9. The Positive Erythritol Response
e four-carbon erythritol is a tetritol that shares many of
the functional and physicochemical properties of the sugar
alcohol family [, , , ]. Erythritol has gained an increas-
ing number of applications in food manufacturing and in
medical and other uses. Owing to the advent of erythritol as
a sweetener in foods, attention was directed at the gastroin-
testinal reactions associated with erythritol consumption.
Following extensive safety evaluations (reviewed in []), it
has been concluded that erythritol is well tolerated in humans
and does not cause any toxicologically relevant eects even
following ingestion of larger quantities. Tolerance studies []
conrmed that repeated ingestion of erythritol in amounts
of  g/kg body weight was well tolerated by humans. No
laxation was observed when adults consumed a single bolus
of erythritol (in a beverage; . g/kg body weight) in 
minutes on an empty stomach. No laxation was observed in
International Journal of Dentistry 
- to -year-old children either. ese consumption gures
indicate the safety of erythritol use, especially when it has
been estimated that the exposure to erythritol via oral health-
care products (such as chewing gums and troches) will be
very low, that is, approximately . g/kg body weight per
day []. e observation that erythritol at doses of up to
. or . g per kg body weight is well tolerated by the
digestive track was demonstrated already by mid-s [,
] and later corroborated by Jacqz-Aigrain et al. []. e
human intestinal microora does not ferment erythritol [].
Erythritol is normally better tolerated than xylitol by humans.
A study carried out in nondiabetic adults at the Louisiana
Technical University showed, however, that a combination of
.goferythritolandgoffructose(usedinequimolar
concentrations) increased watery stools and worsened the
gastrointestinal tolerance []. e authors concluded that
coingestion of equimolar concentrations of fructose and
erythritol may increase carbohydrate malabsorption; that
is,paracellularabsorptionoferythritolcouldalsoenhance
paracellular absorption of fructose in healthy adults. e
results of Kim et al. [] and Putkonen et al. [] suggest that
coingestion of equimolar concentrations of fructose and ery-
thritol increases carbohydrate malabsorption. Combinations
of erythritol-fructose and erythritol-glucose may also cause
untoward eects in dental plaque. Recent studies suggested
that erythritol can have utility value in caries prevention
[, ].
In some experimental animals erythritol may also react
dierent. Guinea pigs were given erythritol with or without
the addition of pectin. e endolymphatic volume of the
animals was investigated to consider the possibility that ery-
thritol is applicable as a therapeutic agent in M´
eni`
ere’s disease
[]. e feces were muddy in all animals with the uptake
of erythritol alone, while muddy or very so feces were not
observed in animals fed a mixture of pectin and erythritol.
10. Conclusions and Instructions
(i) Various gastrointestinal discomforts have been
knowntohumansforthousandsofyears.Osmotic
diarrhea, catharsis, meteorism, atulence, and bor-
borygmi (borborygmus) are terms that frequently
appear in this context.
(ii) Osmotic diarrhea may result from the consumption
of too-large doses of dietary sugar alcohols such as
xylitol, -glucitol, -mannitol, maltitol, lactitol, and
isomalt. Also other related substances, such as the
GOS and lactose, may cause similar eects. GOS-type
substances are normal constituents in the seeds of
leguminous plants, such as soya beans and peas.
(iii) Sugar alcohols, along with some oligosaccharides,
have also received attention in food and nutrition
research owing to their prebiotic properties and other
health benets. IBS and functional constipation serve
as examples of common gastrointestinal disorders
whose treatment may benet from the application of
sugar alcohols and certain GOSs.
(iv) Osmotic diarrhea occasioned by excessive consump-
tion of these substances is not a disease, but a simple
osmotic response to the presence of slowly absorbed
carbohydrates in the gut lumen. e presence of
these solutes in the lumen will draw water from
surrounding tissues.
(v) e capacity of the common alditols to cause osmotic
diarrhea depends on their molar mass, symmetry of
themolecule,and,thus,thedetailedcongurationof
the molecule.
(vi) Consumption of erythritol does not normally lead to
any gastrointestinal changes, while that of hexitols (-
glucitol and -mannitol) may cause changes in adults
alreadyattogdailyconsumptionlevels.Xylitol
is better tolerated, the largest safe doses ranging
widely, normally from  g to  g per day. However,
signicant variation may occur. Consumption of dis-
accharide sugar alcohols maltitol, lactitol, and isomalt
may also lead to similar gastrointestinal disturbances.
(vii) e quantity of xylitol currently recommended for
caries limitation is about  g/day or more for adults
and about half that for infants older than  to 
years; younger infants have received smaller quanti-
ties under parental guidance.
(viii) European Union recommends that daily ingestion of
gof-mannitolandgof-glucitolintheform
of commercial food products should bear a warning
statement about possible laxative eects.
(ix) Researchers have not always paid attention to study
conditions, such as comparing administration of
sugar alcohol in plain water versus as part of regular
ber-containing meals or snacks. For example, toler-
ance to xylitol present in beverages (such as lemon-
ades, zzes, and still drinks) normally causes diarrhea
at lower xylitol levels than when present in solid food.
Useofxylitolinabeverage(apartfromasasweetener
in tea of coee) cannot be recommended.
(x) Adaptation to tolerate increasing quantities of xylitol
hasbeenobservedinlong-termfeedingtrials.e
adaptive changes take place in the gut ora and
possibly by enzyme induction in the liver.
(xi) Xylitol, other alditols, and disaccharide sugar alcohols
possessundeniableutilityvalueindietaryandmed-
ical applications. erefore, health-care professionals
should be aware of restrictions and recommendations
regarding their safe and appropriate use.
Competing Interests
e author declares no competing interests with respect to
the authorship and/or publication of this article.
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... Some studies have shown that frequent consumption of sugary snacks was linked to increased odds of constipation [64]. On some occasions, excess intake of certain sugars such as fructose [65] and polyols [65] may be related to very loose stools due to the osmotic effect of these sugars in the gut [65]. However, a relatively high intake of these sugars/sugar alcohols is needed to cause these effects, and the majority of simple sugars in typical Westernized diets are sucrose and glucose [66]. ...
... Some studies have shown that frequent consumption of sugary snacks was linked to increased odds of constipation [64]. On some occasions, excess intake of certain sugars such as fructose [65] and polyols [65] may be related to very loose stools due to the osmotic effect of these sugars in the gut [65]. However, a relatively high intake of these sugars/sugar alcohols is needed to cause these effects, and the majority of simple sugars in typical Westernized diets are sucrose and glucose [66]. ...
... Some studies have shown that frequent consumption of sugary snacks was linked to increased odds of constipation [64]. On some occasions, excess intake of certain sugars such as fructose [65] and polyols [65] may be related to very loose stools due to the osmotic effect of these sugars in the gut [65]. However, a relatively high intake of these sugars/sugar alcohols is needed to cause these effects, and the majority of simple sugars in typical Westernized diets are sucrose and glucose [66]. ...
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Constipation, a disorder of bowel movements, is among the most frequent gastrointestinal complaints in Western countries. Dietary constituents such as inadequate fiber intake have been related to constipation, but discrepancies exist in the findings regarding dietary factors. This study investigated the association between dietary patterns and bowel movements in adults living in Luxembourg. Data from 1431 participants from ORISCAV-LUX 2 (a cross-sectional survey) who completed a 174-item food frequency questionnaire (FFQ) were analyzed. A questionnaire-based constipation score was assessed by a validated scoring system. Confounders such as physical activity and serum/urine indicators were assessed. Women had higher constipation scores than men (p < 0.001). In food group-based regression models, a negative association was found between higher constipation score and intake of grains (Beta = −0.62, 95%CI: −1.18, −0.05) and lipid-rich foods (Beta = −0.84, 95%CI: −1.55, −0.13), while a positive association was found for sugary products (Beta = 0.54, 95%CI: 0.11, 0.97) (p < 0.05). In a nutrient-based regression model, a positive association was found between constipation score and total energy (Beta = 5.24, 95%CI: 0.37, 10.11) as well as sodium intake (Beta = 2.04, 95%CI: 0.21, 3.87), and a negative one was found for total fats (Beta = −4.17, 95%CI: −7.46, −0.89) and starch (Beta = −2.91, 95%CI: −4.47, −1.36) (p < 0.05). Interestingly, neither fruits and vegetables or dietary fiber were significantly associated with constipation. Thus, grains, lipid-rich foods, total fats and starch were associated with a lower constipation score, while sugary products, sodium, and higher energy intake were correlated with higher constipation.
... Unpleasant off-tastes are more prevalent among synthetic sweeteners such as saccharin or cyclamate, which taste bitter or metallic, for example (Chattopadhyay et al., 2014). Laxative effects and flatulence, on the other hand, are more likely caused by sugar alcohols due to their higher intake rates and water-pulling properties (Mäkinen, 2016). ...
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5-Keto-D-fructose (5-KF) is a natural diketone occurring in micromolar concentrations in honey, white wine, and vinegar. The oxidation of D-fructose to 5-KF is catalyzed by the membrane-bound fructose dehydrogenase complex found in several acetic acid bacteria. Since 5-KF has a sweetening power comparable to fructose and is presumably calorie-free, there is great interest