Clinical Nutrition 33 (2014) 483e488

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Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Original article

Assessment of xylitol serum levels during the course of parenteral

nutrition including xylitol in intensive care patients: A case control
studyq
Andrea S. Schneider*, a, Anika Schettler a, Andrea Markowski, Birgit Luettig,
Michael Momma, Claudia Seipt, Johannes Hadem, Michaela Wilhelmi b
Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: Xylitol has been approved for parenteral nutrition and may be beneficial in catabolic
Received 11 April 2013 situations. The aim was to establish an easy method to monitor xylitol serum levels in patients receiving
Accepted 29 June 2013 xylitol and to determine whether xylitol is safe.
Methods: A commercially available xylitol test was validated and used to measure serum levels in
Keywords: 55 patients admitted to our intensive care unit with an indication for parenteral nutrition with xylitol for
Critically ill
at least 24 h. Controls consisted of the most recent 56 patients admitted to the intensive care unit who
Sepsis
received parenteral nutrition without xylitol for at least 2 days. Xylitol serum levels were determined
Antioxidants
Parenteral nutrition
using the test. Adverse events, liver enzymes, lactate, bilirubin, g-glutamyl transpeptidase, and insulin
Nutrient requirement were secondary endpoints.
Early feeding Results: Patients receiving xylitol received 32.6% less insulin than controls. The amount of energy they
received was comparable (xylitol: 810.1; controls: 789.8 kcal). Mean liver enzymes and lactate levels
were similar in both groups. Adverse events considered attributable to xylitol did not occur. Xylitol did
not accumulate in patients’ blood and returned to near baseline values one day after parenteral nutrition
was stopped.
Conclusions: Parenteral nutrition with xylitol appears to be safe for critical care patients. There were no
signs of hepatoxicity.
Trial registration DRKS: DRKS00004238.
Ó 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

1. Introduction improved survival, nitrogen balance, loss of intracellular glutamine

Xylitol is a sugar substitute that is approved for clinical paren-
teral nutrition (PN). In contrast to glucose that requires insulin to be
metabolized, it is processed via the pentose-monophosphate
shunt.1 This may be beneficial in catabolic situations, because the
release of stress hormones during post-aggression metabolism is
often associated with glucose intolerance and insulin resistance.2,3
Aside from the insulin-independent metabolism, xylitol has been
shown to have other advantages. In rats suffering from intestinal
sepsis Ardawi4 demonstrated that PN with xylitol significantly
q Conference presentation: Barcelona ESPEN Congress on September 8e11th,
2012.
* Corresponding author. Tel.: þ49 511 532 3806; fax: þ49 511 532 3351.
E-mail address: andrea.s.schneider@gmx.de (A.S. Schneider).
a
Both authors contributed equally.
b
Trauma Department, Hannover Medical School, Germany.
in skeletal muscles, and hepatic protein and RNA content compared
to PN without the sugar substitute. Studies in humans showed
rapid metabolism, smaller effects on blood glucose concentrations,
enhanced efficiency in preserving body protein, reduced hepatic
gluconeogenesis, an antiketogenic effect, and a less damaging effect
on the veins.5e8 Thus, parenteral xylitol solutions may be especially
beneficial for intensive care patients.9
So far, the guidelines for PN do not recommend the use of the
sugar substitute xylitol. Its use is still controversial because of
possible hepatotoxicity or nephrotoxicity. To study these effects it is
important to monitor xylitol levels in serum. However, so far, no
simple practical tests are available that quantify serum levels in a
clinical setting. To our knowledge there is only one early study that
assesses xylitol in the serum of intensive care patients using an
enzymatic method.9 However, the method is not described in detail
and measures sorbitol concomitantly. In other studies xylitol is
determined using gas chromatography, which is time consuming,

0261-5614/$ e see front matter Ó 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
http://dx.doi.org/10.1016/j.clnu.2013.06.018
484 A.S. Schneider et al. / Clinical Nutrition 33 (2014) 483e488
expensive, and requires special expertise.10 Xylitol test kits exist,
but they have been established for use in the food industry. They
have not been adapted to measure xylitol in human serum in
clinical situations.
Under in vitro conditions, we validated a test to quantify xylitol
in human serum. This test is based on a first reaction in which a
dehydrogenase oxidizes xylitol to D-xylulose. In a second reaction
NADH reduces iodonitrotetrazolium chloride with the help of
diaphorase to a 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-phenyl-2H-
tetrazolium chloride (INT)-formazan compound. The amount of
INT-formazan that is formed is proportional to the xylitol content
and can be measured at a wavelength of 492 nm using a spectro-
photometer. The test’s accuracy and reliability was assessed by
adding defined amounts of the sugar substitute to control serum
that was definitely xylitol negative. After its validation, the test was
used to assess xylitol levels in the serum of patients receiving PN
with xylitol. To our knowledge, so far no good quality studies have
been published in English that systematically compare PN with and
without xylitol. Only a few older studies of poor quality are avail-
able, mainly in German, which investigate PN with xylitol.5,7e9 The
relevance of the evaluations is limited.
The aim of this case-control study was to determine whether
this method is reliable and safe under actual clinical conditions.
Patients admitted to the intensive care unit who had an indication
to receive PN with xylitol for at least 24 h were included in the
study. Xylitol levels were measured in patients’ serum. In addition
to this primary objective, possible adverse events resulting from
the application of PN containing xylitol and the subsequent xylitol
serum levels were documented. Liver enzymes (aspartate amino-
transferase (AST), alanine aminotransferase (ALT)), lactate, g-glu-
tamyl transpeptidase (g-GT), bilirubin, and daily insulin
requirement were also assessed.
2. Material and methods
2.1. Validation of a test to determine xylitol in human serum
A commercially available test kit for xylitol (K-SORB, Mega-
zyme Deutschland, Gernsheim, Germany) was used according to
the manufacturer’s instructions. Before they were measured,
samples were deproteinized according to the instructions using
Carrez solutions. Defined amounts of xylitol (SigmaeAldrich
Chemie, Munich, Germany) were added to control serum from a
healthy donor who was definitely negative for sugar substitutes.
Since measurement errors due to turbidity were possible
(depending on the amount of sample in the cuvette), different
sample volumes and concentrations were tested to assess the
test error and to determine the range in which the test is accu-
rate. This volume was then used to measure sera from patients
who had received PN with xylitol. Samples were measured at
492 nm using a spectrophotometer (Hitachi U-2000, Mannheim,
Germany).
2.2. Patients and study design
This was a case-control study (registered at DRKS:
DRKS00004238) performed at the trauma intensive care unit at the
Hannover Medical School. It conforms to the ethical guidelines of
the Declaration of Helsinki (1996) and was approved by the ethics
committee of the Hannover Medical School. Consecutive adult
patients who had been admitted to the intensive care unit for a
maximum of 3 days before PN and had an indication to receive PN
with xylitol for at least 24 h were included in the study over a
period of about 8 months. Written informed consent was obtained
from the patients or their next of kin. For the determination of
xylitol, residual serum samples taken as part of routine care were
used. Patients had to meet the following inclusion criteria:
admission to the intensive care unit at Hannover Medical School for
a maximum of 3 days before PN and PN containing xylitol for at
least 24 h.
The retrospective control group consisted of the most recent 56
patients who had been admitted to the Hannover Medical School
intensive care unit for a maximum of 3 days before receiving PN
prior to May 31, 2011 and who had received PN without xylitol for
at least 2 days. Until this date PN at the facility did not include
xylitol on a regular basis. From May 31, 2011 on, there was a change
of standard hospital procedure and all trauma patients received PN
with xylitol unless indicated otherwise. Patients from the control
group were admitted between December 7, 2008 and May 30, 2011.
Patients receiving PN with xylitol entered the trial between May 31,
2011 and February 11, 2012.
The observation period was day 0 (before PN containing
xylitol was applied) up to day 7. According to our nutritional
standard, patients received PN with xylitol via a multi-chamber
bag (Nutriflex Combi, B. Braun, Melsungen, Germany) plus an
MCT/LCT lipid composite (Lipofundin 20%, B. Braun) and a
preparation containing water-soluble and lipid-soluble vitamins
and trace elements as a 24 h infusion via a central venous
catheter. The ingredients of the solutions are shown in Table 1.
The only difference between the PN of the two patient groups
was that the group receiving xylitol (50 g) was given 100 g
glucose in a 2-chamber bag while the controls received 150 g in
a 3-chamber bag. Both groups received MCT/LCT lipids. If
indicated, patients were administered enteral nutrition at a
maximum of 500 kcal/d at the earliest on day 4. A maximum of
120 g xylitol was given per day. Blood samples were taken once a
day on day 0 up to 7 at about the same time as part of routine
care. Samples were stored at 4  C until they were tested. Xylitol
serum levels (mg/dL) were determined within 14 d of blood
sampling. If necessary to maintain normoglycemia, patients
received insulin to keep their plasma glucose level at a range of
6.5e9 mmol/L. The maximum insulin dose was set at 8 IU per
hour (concentration: 1 IU per mL). Adjustments of the insulin
dose were based on whole-blood glucose measurements at 2e
6 h intervals. Each sample was deproteinized and tested in
duplicate against a standard xylitol solution according to the
manufacturer’s instructions (Megazyme). In addition, the amount
of infused xylitol (g/d) was calculated. Secondary parameters
were liver enzymes (AST, ALT), bilirubin, g-GT, and lactate. More
than twice the initial value was defined as increased. The daily
total insulin requirement and acute kidney failure with the
indication for kidney replacement therapy were documented.
Data were collected using the documentation and archive data-
base of the Hannover Medical School (ALIDA, MHH, Hannover
Table 1
Composition of parenteral nutrition given to each study group.
Xylitol group Control group
NutriflexÒ Combi þ Lipofundin 20% NutriflexÒ lipid plus
Volume (mL) 1250a 1250
Energy (kcal) 1277 1265
Carbohydrate (g) 150 150
Glucose 100 150
Xylitol 50 0
Fat (g) 50 50
Amino acids (g) 50 48
Electrolytes 239 198
(mmol)
a
1000 ml NutriflexÒ Combi þ 250 mL Lipofundin MCT/LCT 20%.
 A.S. Schneider et al. / Clinical Nutrition 33 (2014) 483e488 485

Measured xylitol value

45 3. Results
40
35 3.1. Xylitol test can be used to measure xylitol levels in human
30 serum
(mg/dL)

25
20 The difference between the nominal and measured xylitol
15 concentrations was assessed. The mean values that were deter-
10 mined using the test were 0.815  0.011 (actual 0.8) and
2.079  0.073 (actual 2.0) mg/dL. The mean errors were 1.8 and
5
3.9%, respectively (n ¼ 5 each). Figure 1 demonstrates that the
0
actual and the measured xylitol concentrations were comparable at
0 4 10 20 30 40 a concentration ranging from 0 to 40 mg/dL. The mean xylitol level
Xylitol-concentration (mg/dL) in sera from patients who had received PN with xylitol was 3.4 mg/
dL (range 0.00e7.84; n ¼ 20).
Fig. 1. Comparison of actual vs. measured xylitol concentrations.

3.2. Patients in the xylitol and control groups were comparable

Germany) and the intensive care unit database m.life (medisite
Systemhaus Ltd., Hannover, Germany).
2.3. Statistics
This study was performed as a case-control study. Based
on our experience of the previous 2 years, we assumed that
about 100 patients per year would have an indication for PN. The
sample size was calculated at 50 patients to determine a differ-
ence of 10% with a probability of 80%. Means and standard
deviations were calculated and descriptive statistical analyses
performed. Differences between the two patient groups were
tested using Student’s T-test. If mentioned, the chi-square
test was used instead. P-values of <0.05 were considered
significant.
This case-control study included 55 patients who received PN
containing xylitol for at least 24 h. We screened 423 patients over an 8
month period and recruited 58 subjects (Fig. 2). However, 3 patients
in the group receiving PN with xylitol died. One patient (88 years old)
died of respiratory failure due to lung metastases and the second (age
87 years) died of unknown cause. Both patients had not started PN
with xylitol and were not included in the analysis. The third patient
(54 years old) died on day 5 of treatment of aorta vertebralis
dissection with stroke after a fall. He was included in the analysis. One
patient who had started PN with xylitol was given PN without xylitol
during the course of the study and excluded from the analysis.
Table 2 summarizes the patient characteristics of the 2 patient
groups. There were no significant differences in the two patient
populations regarding their baseline characteristics.

Assessed for eligibility

(n = 423)

Excluded (n = 362)

Enrollment Not meeting inclusion criteria

(n = 362)
(n = 58)

Retrospective assessment (n = 1749)

Not meeting inclusion criteria (n = 1693)

Allocated to xylitol group (n = 58)

Received PN with xylitol (n = 55)
Did not receive PN with xylitol
(n = 3) Allocation
Retrospective allocation to control
Reason: 2 died before treatment;1 group (n = 56)

received incorrect PN

Analyzed (n = 55) Analyzed (n = 56)

Excluded from analysis (n = 3) Analysis Excluded from analysis (n = 0)

Fig. 2. CONSORT flow diagram showing the number of patients screened, recruited, and dropped.
486 A.S. Schneider et al. / Clinical Nutrition 33 (2014) 483e488

Table 2
Patients’ baseline characteristics. 100 *
PN with xylitol Controls Difference between
groups (p-valuea) 90
Gender n(%) n(%)
Male 36(65.5) 42(75.0) 0.27
80
Female 19(34.5) 14(25.0)

Insulin requirement per day (IU)

Age years 47.7  19.8 50.7  21.9 0.45
(range) (18e84) (18e89) 70

Diagnosis n(%) n(%) 0.85

Polytrauma 40(72.7) 38(67.9) 60
Fall 8(14.5) 10(17.9)
Other 7(12.7) 8(14.3)
50
Diabetes n(%) n(%) 0.76
5(9.1) 6(10.7)
40
SAPS score 30.7  10.1 29.3  11.5 (8e61) 0.49
(range) (6e58)
a
P-values were calculated using the c2etest for all parameters but age. 30

3.3. PN with xylitol was safe for intensive care patients

Mean aminotransferase levels did not differ between patients
receiving xylitol and patients who were not given the sugar substitute
(AST: 72.1  71.8 (n ¼ 55) vs. 68.4  111.5 IU/L (n ¼ 56), respectively,
p ¼ 0.83 and ALT: 52.4  45.3 (n ¼ 55) vs. 62.1  123.6 IU/L (n ¼ 55),
respectively, p ¼ 0.59). The mean maximum increase in AST was
1.2  1.0 vs.1.7  1.4 IU/L (p ¼ 0.06) and in ALT 1.9  2.1 vs. 2.2  2.5 IU/
L (p ¼ 0.50), respectively. There was no significant difference in the
mean increase by more than twice the baseline value for AST or ALT
(p ¼ 0.17 and p ¼ 0.66, respectively, c2-test) for both groups.
Lactate levels were similar (1.2  0.5 (n ¼ 55) vs. 1.1  0.5 mmol/
L (n ¼ 50), respectively, p ¼ 0.42) and within the normal range
(0.6e4.0 mmol/L). The mean maximum increase from baseline was
not significantly different between the groups (1.1  0.7 (n ¼ 55)
and 1.1  0.5 mmol/L (n ¼ 50), respectively, p ¼ 0.66).
Mean bilirubin levels were similar in the group receiving PN
with xylitol and the group that did not (xylitol group: 33.1  72.1
(n ¼ 33); controls: 26.5  30.6 mmol/L (n ¼ 44), p ¼ 0.56). There was
no difference in the maximum increase from baseline up to day 7
between the groups (1.6  1.9 (n ¼ 33) and 2.0  1.7 mmol/L
(n ¼ 44), respectively, p ¼ 0.38).
Mean g-GT levels were similar (99.3  104.8 (n ¼ 34) and
146.7  145.9 IU/L (n ¼ 43), respectively, p ¼ 0.10) in the xylitol and
control group. The mean maximum increase in g-GT levels was also
the same between the groups (6.3  8.6 (n ¼ 34) and 6.7  7.7 IU/L
(n ¼ 43), respectively, p ¼ 0.82).
Adverse events considered attributable to PN containing xylitol
did not appear to occur.
20
10
0
1
Xylitol group Control group
Fig. 3. Comparison of daily insulin requirement. The number of patients receiving PN
with xylitol were n ¼ 55 and controls were n ¼ 56. Values are given as means  SD. The
asterisk depicts a significant difference between the two groups (p ¼ 0.01).
3.5. Xylitol did not accumulate in the serum of patients receiving
PN with xylitol and quickly returned to baseline values
As is shown in Fig. 4, the amount of xylitol that was infused only
had a slight effect on the level in blood of patients receiving PN with
xylitol. Of the xylitol values 97.2% were below 10 mg/dL. The trend
line is nearly horizontal indicating that there was no accumulation
of xylitol.
In addition, the measured levels were near the detection limit of
0.5 mg/dL. The mean xylitol level was 3.7  3.0 mg/dL (n ¼ 323).
Already one day after PN with xylitol was terminated, levels
returned almost to values before PN with the sugar substitute was
administered (mean xylitol level 3.6  2.0 decreased to
0.88  1.2 mg/dL (n ¼ 14), range 1.5e7.9 and 0.0e3.9 mg/dL,
respectively). The difference in the levels before and after termi-
nation was significant (p ¼ 0.0002).

3.4. Patients given PN with xylitol received similar amount of

energy, but required less insulin 4. Discussion

Mean blood glucose values at baseline were similar in the
groups receiving PN with and without xylitol (7.0  0.7 vs. 7.0  0.8
(range 6.8e7.2 and 6.6e7.2), respectively, p ¼ 0.78). Both patient
groups received the same mean amount of energy via PN per day as
carbohydrates plus xylitol and carbohydrates (PN with xylitol:
810.1  147.6 kcal (n ¼ 55) and controls: 789.8  110.7 kcal (n ¼ 56),
p ¼ 0.41). One of the secondary endpoints of this study was the
amount of insulin patients required to keep their serum glucose
level at 6.5e9 mmol/L. Twenty percent of the patients receiving
xylitol had stable glucose levels and did not need insulin compared
to only 7.1% of the controls (p ¼ 0.04). Figure 3 shows that subjects
receiving PN with xylitol had a significantly lower insulin require-
ment than control patients.
This case-control study was done to determine whether a
commercially available xylitol test kit that is normally used in the
food industry is reliable and safe to assess xylitol in human serum
under actual clinical conditions. We first validated the xylitol test.
Our results showed that it was accurate (error 3.9%) in measuring
xylitol levels found in serum at a range of 0e40 mg/dL. An earlier
poor quality study that also measured xylitol in serum of 10 pa-
tients enzymatically did not describe the method used in detail.9 In
addition, their test concomitantly measured sorbitol which meant
that these sugar substitutes could not be differentiated. Other
studies used gas chromatography to quantify xylitol.11,12 This is of
course valid. However, the method is tedious and time consuming
and requires special skills.
 A.S. Schneider et al. / Clinical Nutrition 33 (2014) 483e488
Fig. 4. Serum levels of xylitol vs. amount of xylitol infused in 24 h.
Although there is still controversy about whether PN with
xylitol is safe and benefits critical care patients, to our knowledge
there is no study that directly compares complete PN with and
without xylitol with the only difference being that one group
receives less glucose and in exchange xylitol. Table 3 lists the
studies that have compared PN with and without xylitol. Leute-
negger et al.9 compared different PN, but not all results were sta-
tistically evaluated. Georgieff et al.11 also compared PN with and
without xylitol, but they gave no information on hepatoxicity. In
addition, their PN formula was not complete i.e. it contained only
xylitol or glucose and amino acids. Our study is the first to sys-
tematically compare serum from patients receiving complete PN
with and without xylitol. We compared serum from 55 patients
receiving PN containing xylitol with serum from a retrospective
group (n ¼ 56) who received the same amount of energy, amino
acids, and lipids. The only difference was that control patients
received 150 g glucose per bag while patients in the xylitol group
received 100 g glucose plus xylitol per bag. The patients in both
groups were similar with regard to age, gender, diagnoses, diabetes,
and SAPS score and, thus, comparable.
There were no clinical or laboratory signs of hepatotoxity due to
xylitol. The groups showed no difference with respect to AST levels
or an increase of the level by at least double. Leutenegger et al.9
who studied patients who were given PN with and without
Table 3
Studies that compare xylitol and glucose as energy sources in parenteral nutrition (PN).
Studies Main findings
Georgieff M et al. 198111 Lower glucose levels and insulin
requirement in the xylitol group
Leutenegger A et al. 19849 Lower glucose levels and insulin
requirement in the xylitol group
Schricker T et al. 19937 Lower glucose levels in xylitol and
xylitol/glucose groups in both studies
Schricker T et al. 19948 Lower glucose levels in the xylitol
group, lower increase in serum insulin
levels
487
xylitol also determined AST. They did not mention whether there
was a significant difference between the groups. The values appear
similar since standard deviations depicted in the graph are high.
Also the results are based on few patients (n ¼ 10). In our study
mean ALT, g-GT, and bilirubin levels were comparable in both pa-
tient groups and also did not differ in their mean increase. Similar
to our study Leutenegger et al.9 found slight hyperbilirubinemia in
both patient groups, but they did not compare the groups directly.
Additionally, we did not observe metabolic decompensation due
to xylitol. Lactate was similar in both groups and within the normal
range. This is in agreement with Leutenegger et al.,9 but in contrast to
results from Georgieff et al.11 who described higher lactate values in
the xylitol group. However, these were also within the normal range.
Schricker et al.7,8 observed lower values in the sugar substitute group.
However, patients in this study as already mentioned did not receive
complete PN. Aside from xylitol or glucose, the infusion only included
amino acids and the authors did not give information on the exact
composition of the energy supply. Furthermore, the number of
patients included in all three studies was small (n ¼ 8e18).
We observed no adverse effects considered attributable to PN in
the group receiving xylitol. Furthermore, there was no difference
with regard to adverse events between the two patient groups.
Therefore, PN with xylitol was safe for intensive care trauma pa-
tients who, based on experience, are metabolically more stable and
usually do not have preexisting liver diseases.
The mean blood glucose values at baseline for both groups were
comparable. However, the xylitol patient group received signifi-
cantly less insulin during the course of the study with the same
energy intake. The requirement was 32.6% lower and 20.0% did not
need insulin at all. This is in accordance with results of López
Martinez et al.13 who show that patients receiving PN with xylitol
also had a lower insulin requirement. This means that these
patients had a better and more constant metabolic adjustment and,
thus, a lower risk of steatosis hepatis.
Mean xylitol levels (3.2 mg/dL) were lower in our study as
compared to values found in the Georgieff study (about 7.5 mg/
dL).11 This was most likely due to differences in the amount of
xylitol that were given which was about twice the amount we gave,
and perhaps to differences in the test method. We found no accu-
mulation of xylitol in patient serum after they had stopped
receiving PN with xylitol. Serum levels returned almost to baseline
values within 24 h. Although there is no defined cut-off point
known for xylitol, the levels were at a very low range (close to the
detection level of 0.5 mg/dL).
We conclude that PN with xylitol may be safe for critical care
trauma patients. There were no signs of hepatoxicity due to the
sugar substitute. In addition, the lower insulin requirement may be
Difference to our study
PN formula contained no lipids, n ¼ 11e13 per group;
gaschromatographic xylitol measurement; postoperative
gastric patients; PN: 5 d
Only xylitol group received lipids; n ¼ 10 per group;
enzymatic xylitol/sorbitol measurement which is not
described; trauma patients
Study 1: Compared glucose and xylitol PN in postoperative
pancreatitis or abdominal abscess patients; Study 2:
Compared glucose and xylitol/glucose (1:1) PN in sepsis
patients; n ¼ 8 per group; PN: 6 h; the exact formulations
of PN is not given; xylitol was not assessed
Compared glucose and xylitol/glucose (1:1); n ¼ 6 per
group; postoperative cardiac patients PN: 36 h; the exact
formulations of PN is not given; xylitol was not assessed
488 A.S. Schneider et al. / Clinical Nutrition 33 (2014) 483e488
beneficial to patients. Although the patient number we observed
was higher than have previously been studied, larger studies are
needed to determine whether all critical care patients or ones with
certain diseases would benefit from PN with xylitol.
Statement of authorship
ASS, AS, MM, CS, BL, JH, and MW carried out the study and data
analyses and drafted the manuscript. AM and AS carried out the
sample analyses and AM performed the statistical analysis. ASS, AS,
and MW conceived of the study, and participated in its design and
coordination. All authors read and approved the final manuscript.
Conflict of interest
Andrea Schneider has given conference presentations for B.
Braun (Melsungen, Germany).
Acknowledgments
The authors would like to thank the staff of the trauma unit for
their support in performing the study and Heinz Geerlings for help
with statistical analyses.
Sources of funding: This study was supported by B. Braun
(Melsungen, Germany). The company was not involved in the study
design, in the collection, analysis, or interpretation of data, in the
writing of the manuscript, and in the decision to submit the
manuscript for publication.
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