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Review
Nutrafoods (2015)
DOI 10.1007/s13749-014-0067-5
Health effects of erythritol
Daniëlle M.P.H.J. Boesten, Gertjan J.M. den Hartog, Peter de Cock,
Douwina Bosscher, Angela Bonnema, Aalt Bast
Received: 7 August 2014 / Accepted: 3 November 2014
© Springer – CEC Editore 2015
Correspondence to:
Daniëlle Boesten
danielle.boesten@maastrichtuniversity.nl
Abstract
Erythritol (1,2,3,4-butanetetrol) is a non-caloric C4
polyol made by fermentation that has a sweetness
60–70% that of sucrose. The safety of erythritol has
been consistently demonstrated in animal and hu-
man studies. Erythritol has a higher digestive toler-
ance compared to all other polyols because about
90% of the ingested erythritol is readily absorbed
and excreted unchanged in urine. Erythritol is used
in a wide range of applications for sweetening and
other functionalities, e.g., in beverages, chewing
gum and candies. In this review, we summarise the
health effects of erythritol described in the literature.
We focus on studies involving the anti-cariogenic
and endothelial protective effects of erythritol. We
conclude that erythritol could be of great importance
and could be considered to be the preferred sugar
substitute for a rapidly growing population of people
with diabetes or pre-diabetes to reduce their risk of
developing diabetic complications.
General characteristics
Erythritol (1,2,3,4-butanetetrol) is a four-carbon
sugar alcohol, or polyol, and a meso-butanetetrol
(Fig. 1). It occurs naturally in some mushrooms,
some fruits (e.g., watermelon, grapes and pears) and
in fermented foods including wine, cheese, sake
and soy sauce [1, 2]. Consumption of erythritol nat-
Keywords:
erythritol, sweetener,
health effects,
anti-cariogenic,
endothelial, diabetes
13
Daniëlle M.P.H.J. Boesten (•), Gertjan J.M. den Hartog, Aalt Bast
Department of Toxicology
Maastricht University
PO Box 616
6200 MD Maastricht, The Netherlands
tel: +31 43 3881340
danielle.boesten@maastrichtuniversity.nl
Peter de Cock, Douwina Bosscher
Cargill R&D Center Europe
1800 Vilvoorde, Belgium
Angela Bonnema
Cargill R&D Center
Minneapolis, MN, USA
Figure 1 Two possible stereoisomers of 1,2,3,4-butanetetrol are
shown. On the left: erythritol, the 2R,3S isomer.
Although this compound contains two asymmetric
carbon atoms, the overall molecule is achiral because
it contains an intramolecular plane of symmetry.
This plane of symmetry is absent in the compound
on the right, D-threitol, which is therefore chiral: it has
an enantiomer (mirror image) L-threitol (not shown)
HO
HO
OH
OH
2R,3S-1,2,3,4-butanetetrol
erythritol
2R,3R-1,2,3,4-butanetetrol
D-threitol
**
HO
HO
OH
OH
**
erythritol does not affect reproductive performance
or fertility of parental rats. In addition, no adverse
effects on the developing foetus were observed [2,
5–7]. Erythritol does not have mutagenic potential,
as observed in the Ames test and chromosomal
aberration test [2, 5, 8, 9].
In summary, animal toxicological studies and clin-
ical studies have consistently demonstrated the
safety of erythritol. Therefore, it is not expected
that erythritol will cause adverse effects under the
conditions of its intended use in food.
Metabolic fate
The metabolic profile of erythritol is not like that
of any other polyol, which gives rise to some of
erythritol’s unique properties. Erythritol is readily
and virtually completely absorbed from the small
intestine via passive diffusion similar to fructose.
Fructose transport can also occur via GLUT2 trans-
port with absorption enhanced in the presence of
glucose due to greater GLUT2 insertion in the apical
membrane as SGLT1 transports glucose. This ex-
plains the enhanced absorption of fructose in the
presence of glucose. In addition, the presence of
glucose has been shown to enhance paracellular
flow due to the opening of tight junctions resulting
in increased absorption of small solutes [10]. En-
hanced GLUT2 insertion and enhanced paracellular
flow in the presence of glucose has been hypothe-
sised to be the same pathway with altered functions
in the absence/presence of glucose. However, this
hypothesis does not support the differences noted
for minor increases in small solute transport com-
pared to the greatly enhanced transport of fructose
when glucose is present [11, 12]. As erythritol is
readily absorbed on its own, the impact of the pres-
ence of glucose on erythritol absorption would be
minimal and has not been investigated to date. Af-
ter absorption, erythritol is distributed throughout
the body, with maximum plasma concentrations
occurring within the first 2 h of digestion. Up to
90% is excreted unchanged in the urine [5, 13, 14].
Unabsorbed erythritol may be subjected to microbial
urally occurring in foods has been estimated to be
80 mg/day (~1.3 mg/kg body weight/day) in the
United States [2]. Erythritol is also found endoge-
nously in human and animal tissues and body fluids
including blood, urine and cerebrospinal fluid [2].
Erythritol is a white, anhydrous, non-hydroscopic
and crystalline substance. It is 60–70% as sweet as
sucrose [3]. Although erythritol was first isolated in
1852, it took until 1990 for it to be marketed as a
new natural sweetener in Japan. Currently, the use
of erythritol in foods has been approved in more
than 60 countries. The range of applications includes
as a tabletop sweeteners and in beverages, chewing
gum, chocolate, candies and bakery products [3].
Manufacturing process
Large-scale production of erythritol uses fermenta-
tion. Pure glucose, sucrose or glucose from maize
(as a source of starch) is used as a starting material.
Starch is extracted from the maize, and through hy-
drolysis the starch chains are broken down into glu-
cose molecules, which are fermented into erythritol
using an osmophilic yeast, like Moniliella pollinis.
After fermentation, yeast cells and other impurities
are removed by filtering. Once the fermentation
broth is filtered, erythritol is purified by ion ex-
change resin, activated charcoal and ultrafiltration.
In the last step, crystallisation, the broth is cooled
down and erythritol precipitates from the solution
yielding crystals with over 99% purity [3, 4].
Safety
A number of toxicological studies have been per-
formed to evaluate the safety of erythritol. These
have been extensively discussed in reviews by Bernt
et al. and Munro et al. [2, 5].
In summary, based on acute toxicity studies, ery-
thritol is classified as essentially non-toxic after
oral administration. Subchronic studies further sup-
port the safety of erythritol. Chronic studies (up to
2 years) revealed that erythritol has no effect on
survival or carcinogenicity [2, 5].
Even at high doses (up to 16 g/kg body weight),
Nutrafoods (2015)
13
patients. No effect on plasma glucose or insulin
levels was observed within 3 h after ingestion of 1
g/kg body weight erythritol [14]. Ingestion of 0.3
g/kg body weight erythritol did not influence serum
glucose or insulin levels, whereas the same dose of
glucose rapidly increased these levels [21].
Health effects
Dental health
Mutans streptococci play an important role in the
development of dental plaque. They attach to the
biofilm on teeth and produce glucosyltransferase.
This enzyme is responsible for the synthesis of in-
soluble glucan plaque material. Glucans and the
bacteria accumulate on the teeth and are known
as dental plaque. When large amounts of plaque
form on teeth in the presence of sugar, the mutans
streptococci produce lactic acid. The acid weakens
tooth enamel through demineralisation, ultimately
causing dental caries [3, 22].
When erythritol was incubated with a range of mu-
tans streptococci species, no lactic acid production
was observed. Furthermore, it was not used for
growth or plaque formation by the mutans strep-
tococci [23]. Another study showed that erythritol
inhibited the growth of several strains of mutans
streptococci strains [24]. A study by Hashino et al.
showed that erythritol has inhibitory effects on
Porphyromonas gingivalis and Streptococcus gordonii
heterotypic biofilm development via several path-
ways, including a decrease in DNA/RNA synthesis,
decreased extracellular matrix production and al-
terations of dipeptide acquisition and amino acid
metabolism [25].
This was also supported by an in vivo study into
the effects of 6-month use of erythritol, xylitol and
glucose (in the form of chewable tablets and tooth-
paste). Erythritol and xylitol led to a significant re-
duction in the amount of plaque and saliva levels
of mutans streptococci. In addition, a reduction in
the amount of dental plaque was observed in sub-
jects that had received erythritol and xylitol [24].
A 3-year clinical trial also found that erythritol pro-
fermentation in the colon. However, studies with
13C-erythritol showed no increase in breath 13CO2
and H2, which indicated that erythritol was not
metabolised by the host [15]. The inability of faecal
flora to metabolise erythritol was confirmed in in
vitro studies with fermentation times of up to 24 h
[15, 16]. The potential for erythritol fermentation
exists with exceedingly high doses, much greater
than those represented with current intake [17].
Erythritol has much higher digestive tolerance than
other polyols. This can mainly be attributed to the
fact that it is readily absorbed and only a small
fraction reaches the colon. Other polyols are poorly
absorbed, which can provoke undesirable intestinal
effects when they are consumed in excessive quan-
tities. These effects can occur due to gas formation
by fermentation (leading to flatulence) or as a result
of osmotic effects (leading to laxative effects). Gas-
trointestinal responses of persons ingesting erythri-
tol at up to 0.8 g/kg body weight were comparable
to those of sucrose [13]. Repeated ingestion of ery-
thritol at daily doses of 1 g/kg body weight did not
show more frequent gastrointestinal effects than
sucrose, indicating that erythritol was well tolerated
[18]. When 35 g of erythritol was consumed in a
drink, it was well tolerated, while at a dose of 50 g,
only significant increases in borborygmi and nau-
sea were observed. The consumption of 35 and 50
g of xylitol in the same study induced significant
gastrointestinal distress [19]. The maximum dose
of erythritol not causing laxation was calculated
to be 0.80 g/kg body weight for females and 0.66
g/kg for males [20]. However, the maximum dose
is also dependent on the delivery method. Con-
sumption of erythritol with solid foods is tolerated
at a higher intake level than with beverages, be-
cause digestion of food products is slower, provid-
ing a longer period for absorption to occur [19].
Because of its metabolic profile, erythritol does not
provide energy to the body and therefore has a
caloric value of 0 calories/g [3]. In addition, ery-
thritol does not raise plasma glucose or insulin lev-
els and can therefore be regarded as safe for diabetic
Nutrafoods (2015)
13
jor structural requirement for superoxide scav-
engers. The ability of erythritol to scavenge radicals
in a cellular system was tested with a haemolysis
assay. Erythritol delayed radical-induced haemolysis
in red blood cells in a concentration-dependent
manner [30].
The reaction of erythritol with hydroxyl radicals
was also demonstrated in an in vivo model using
diabetic rats. The rats were fed 1000 mg/kg per day
for a period of 3 weeks after diabetes was induced
by streptozotocin. The urine of the rats was inves-
tigated for the presence of two oxidative metabo-
lites of erythritol: erythrose and erythrulose. The
amount of erythrose in the urine was highest in
the diabetic group fed with erythritol, indicating
that erythritol scavenged hydroxyl radicals pro-
duced during hyperglycaemia in these rats [30].
In another in vivo study, by Yokozawa et al., an-
tioxidant properties of erythritol were also investi-
gated [31]. Several doses of erythritol (100, 200 and
400 mg/kg body weight) were orally administrated
to streptozotocin-induced diabetic rats for 10 days.
The highest dose resulted in a decrease of 5-hy-
droxymethylfurfural (5-HMF) levels, a marker for
the extent of glycosylation of serum protein. In
addition, thiobarbituric acid reactive substances
levels of serum, liver and kidney were lower in the
groups that received erythritol, indicating a reduc-
tion of lipid peroxidation (a marker of oxidative
stress). This study also found a reduction in serum,
liver and kidney glucose levels and a reduction in
serum creatinine when rats were given erythritol.
They conclude that erythritol is able to affect glu-
cose metabolism and reduce lipid peroxidation and
kidney damage caused by hyperglycaemia [31].
Endothelial protective effects
Most of the complications that arise from chronic
hyperglycaemia find their origin in damaging the
endothelium, a thin layer of cells lining the car-
diovascular system [32–34]. The endothelium plays
an important role in numerous physiological func-
tions with one of the most important endothe-
motes dental health [26]. In this study, initially, 7–
8-year-old children were given erythritol, xylitol
or sorbitol candies containing 7.5 g of the polyol
daily for three years. Erythritol consistently reduced
the amount of dental plaque during the follow-up
period. In addition, the plaque of erythritol-receiv-
ing subjects showed a reduction in the levels of
acetic acid, propionic acid and lactic acid. Further-
more, erythritol consumption led to lower salivary
and plaque mutans streptococci counts compared
with other groups. This long-term study also in-
vestigated the impact of polyol consumption on
dental caries development [27]. It was found that
less children in the erythritol group developed
enamel or dentin caries over the three years (4.6%
vs. 5.5% in the sorbitol and 5.8% in the xylitol
group). In addition, in the erythritol group, a lower
number of enamel caries tooth surfaces developed
to dentin caries (1.3% vs. 1.7% in the sorbitol and
2.0% in the xylitol group). Furthermore, the time
to development of enamel/dentin and dentin caries
lesions (surfaces) was statistically significantly
longer in the erythritol group compared to the sor-
bitol or xylitol group. These studies demonstrate
that erythritol can reduce the risk of dental caries
development.
Antioxidant properties
It is well known that the polyol mannitol is a hy-
droxyl radical scavenger [28, 29]. Since erythritol
closely resembles the structure of mannitol, den
Hartog et al.investigated the hydroxyl radical scav-
enging capacity of erythritol and several other poly-
ols with a test tube assay. A correlation between
the number of hydroxyl groups in the investigated
compound and its rate constant for the reaction
with hydroxyl radicals was found. Erythritol proved
to be an excellent hydroxyl radical scavenger, with
a rate constant of 1.18×109M–1 s–1 [30].
In the same study, the ability of erythritol to scav-
enge superoxide radicals was investigated in a test
tube assay. Erythritol proved to be inert towards
superoxide radicals, probably because it lacks a ma-
Nutrafoods (2015)
13
lium-dependent vascular relaxation was prevented
by erythritol in these rats [30].
To further investigate the endothelium protective
effect, a study in endothelial cells was performed
[36]. The cells were exposed to normal and high
glucose concentrations and targeted and transcrip-
tomic approaches were used to examine the effect
of erythritol under these conditions. Overall, it was
found that erythritol by itself (i.e., under non-dia-
betic conditions) has no effect on the endothelial
cells. However, under high glucose conditions, ery-
thritol was able to reverse a number of deleterious
effects. The most striking observation was that ery-
thritol reversed the direction of change of 148 of
the 153 transcripts altered by high glucose incuba-
tion. Another finding was that erythritol did not
seem to affect single endpoints, but rather had an
effect on multiple targets – a mode of action which
is not uncommon for natural compounds [37, 38].
A pilot study on the effects of erythritol in patients
with type 2 diabetes also revealed protective effects
on vascular function [39]. In this study, 24 subjects
consumed 12 g of erythritol three times daily for 4
weeks. Subjects were tested at baseline and after 4
weeks. In addition, acute and acute-on-chronic ef-
fects before and 2 h after consumption of 24 g ery-
thritol at baseline and follow-up visit were meas-
ured. Acute consumption of erythritol improved
small vessel endothelial function as measured by
fingertip peripheral arterial tonometry (EndoPAT).
Chronic erythritol consumption showed a decrease
in central pulse pressure and a trend towards a
lower carotid-femoral pulse wave velocity. These
findings suggest that erythritol can reduce arterial
stiffness and improve small vessel endothelial func-
tion. However, this was a pilot study without a
control group and a modest sample size. To validate
the findings of this study, a randomised, placebo-
controlled study is required [39].
Conclusion
Erythritol is a non-caloric bulk sweetener which
has been shown in multiple studies to reduce the
lium-derived mediators being the soluble gaseous
radical nitric oxide (NO), responsible for vascular
relaxation. Endothelial dysfunction occurs when
the endothelium loses its physiological properties.
This has been linked to diabetes through the
demonstration of impaired endothelial-dependent
vasodilatation [35].
The study of den Hartog et al. also focused on the
effect of erythritol on endothelial function. This
was investigated in rings prepared from the thoracic
aorta. Carbachol concentration response curves
were recorded for the different groups (Fig. 2). In
diabetic rats, the ex vivo carbachol response is
smaller and requires higher concentrations than
in control rats. This indicates that the endothelium
of these rats is damaged. Since the carbachol re-
sponse is mediated by NO, the diabetic rats seem
to be incapable of generating sufficient NO to in-
duce maximum relaxation. In diabetic rats fed with
erythritol, the carbachol response curve was similar
to control rats, indicating that the loss of endothe-
Nutrafoods (2015)
13
Figure 2 Carbachol concentration–response curves recorded
with aortic rings from normoglycaemic rats (N),
diabetic rats (D), normoglycaemic rats that
had consumed erythritol (NE) and diabetic rats
that had consumed erythritol (DE). In diabetic rats,
the ex vivo carbachol response is smaller and requires
higher concentrations than in control rats.
Erythritol prevents the loss of response to carbachol,
thus maintaining endothelium-dependent vascular
relaxation. Adapted from den Hartog et al. [30].
N NE D
0.2
0.6
0.4
0.0
-0.2
Relaxation (g)
-7 -5 -4-6
log [carbachol]
DE
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Kennepohl E, Bar EA, Modderman J, Bernt WO (1998) Ery-
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toxicological and clinical data. Food Chem Toxicol
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erythritol in rats. Regul Toxicol Pharmacol 24:S237–246
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Mutagenicity studies on erythritol in bacterial reversion
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Xia T, Gisolfi CV (1997) Fructose transport mechanisms in
humans. Gastroenterology 113:1171–1179
11. Kellett GL, Brot-Laroche E (2005) Apical GLUT2: a major
pathway of intestinal sugar absorption. Diabetes 54:3056–
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12. Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG
(2007) Review article: fructose malabsorption and the bigger
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10.1111/j.1365-2036.2006.03186.x
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testinal response and plasma and urine determinations in
human subjects given erythritol. Regul Toxicol Pharmacol
24:S296–302. doi: 10.1006/rtph.1996.0111
14. Bornet FRJ, Blayo A, Dauchy F, Slama G (1996) Plasma and
urine kinetics of erythritol after oral ingestion by healthy
humans. Regul Toxicol Pharmacol 24:S280–S285. doi:
http://dx.doi.org/10.1006/rtph.1996.0109
15. Hiele M, Ghoos Y, Rutgeerts P, Vantrappen G (1993) Me-
tabolism of erythritol in humans: comparison with glucose
and lactitol. Br J Nutr 69:169–176
16. Arrigoni E, Brouns F, Amado R (2005) Human gut micro-
biota does not ferment erythritol. Br J Nutr 94:643–646
17. Beards E, Tuohy K, Gibson G (2010) Bacterial, SCFA and
risk of caries development. As erythritol does not
influence glucose or insulin levels, it is a good al-
ternative for sugar in patients with diabetes as well
as for people needing or desiring to manage blood
sugar levels due to prediabetes or compromised car-
bohydrate metabolism. In addition, diabetes pa-
tients could benefit from the vascular effects of
erythritol described above. It is expected that in
non-diabetic subjects the endothelium will not be
affected by erythritol. However, in diabetic subjects,
where the endothelium is under diabetic stress,
erythritol could shift a variety of damage and dys-
function parameters to a safer side, as observed in
the in vitro, ex vivo and in vivo studies. Erythritol
can therefore be regarded as a compound that has
protective effects on the endothelium under high
glucose conditions, leading to a prevention or delay
in onset of diabetic complications.
The characteristic of erythritol of having small ef-
fects on multiple targets may also prove to be ben-
eficial. A compound with a strong biological effect
is less suitable for chronic supplementation, as is
needed in diabetes. The alternative is to use a com-
pound with mild protective effects like erythritol.
Erythritol could therefore be of great importance
and could be considered to be the preferred sugar
replacer for a rapidly growing population of people
with diabetes or pre-diabetes to reduce their risk of
developing diabetic complications.
Conflict of interest
This research was financially supported by Cargill Inc. Cargill is
a manufacturer of erythritol and the employer of Peter de Cock,
Douwina Bosscher and Angela Bonnema. Daniëlle Boesten, Gert-
jan den Hartog and Aalt Bast received funding from Cargill.
Human and Animal Rights
This review article does not contain any studies with human or
animal subjects performed by any of the authors.
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