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Intensive Care Unit and
*
Department of Gastroenterology and Hepatology, Department of Internal Medicine IV and
Institute of Medical Statistics and Documentation, University of Vienna, 1090 Vienna, Austria
1To whom correspondence and reprint requests should be addressed.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • Crohn's disease • humans • energy metabolism • enteral nutrition • substrate oxidation
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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);
this might explain weight loss in some patients. In others,
malabsorption and increased intestinal losses have been discussed as a
cause of a negative substrate balance as in other catabolic diseases
(Stokes 1992
). Another etiological factor could be an
increased energy expenditure. Increased energy expenditure and changes
in substrate oxidation have been found in several diseases and have
been linked to weight loss (Wilmore 1991
).
Several authors have measured resting energy expenditure in Crohn's
disease with controversial results: Chan et al. (1986)
found that
patients with Crohn's disease, without fever and sepsis, did not have
increased resting energy expenditure
(REE)2
, whereas Kushner and Schoeller (1991)
found a slight increase in energy
needs in stable outpatients with inflammatory bowel disease. These
conflicting results could be explained in part by the fact that these
authors investigated a rather heterogeneous group of patients with a
wide variation of disease activity. In the study of Chan et al. (1986)
43% of patients were receiving prednisone, which influences substrate
metabolism (Horber et al.1991
).
Parenteral as well as enteral nutrition are used in active Crohn's
disease although the therapeutic mechanism is not known. Improvement of
nutritional status appears to be essential for the anti-inflammatory
effect of nutritional therapy as shown in a recent publication
(Royall et al. 1994b
). In this study, a good
correlation between the achievement of a positive nitrogen balance and
remission after enteral nutrition in Crohn's disease was found.
Pollicino et al. (1991)
studied the effect of cyclic and continuous
total parenteral nutrition on energy expenditure and substrate
metabolism measured by 24-h whole-body calorimetry. They found that a
positive energy balance could easily be achieved in all subjects and
demonstrated net lipogenesis from carbohydrate during parenteral
nutrition. However, their patients had been in the remission phase of
Crohn's disease, were receiving a low dose oral prednisolon therapy
and had already been fed intravenously for at least 1 wk before they
were studied (Pollicino et al. 1991
).
Therefore, data on the effect of enteral nutrition on energy expenditure and substrate oxidation in active Crohn's disease are still incomplete.
In this study, therefore, we investigated energy and substrate metabolism in patients with active Crohn's disease without corticosteroid therapy. Furthermore, we investigated the effect of enteral nutrition on energy expenditure and substrate oxidation rates in these patients. We hypothesized that as in other acute diseases such as infection and trauma, energy expenditure is increased, the respiratory quotient (RQ) is decreased in patients with acute Crohn's disease and enteral nutrition is able to normalize changes in substrate oxidation rates.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Thirty-two patients with active Crohn's disease participated in the
study. The diagnosis of Crohn's disease was established by generally
accepted criteria in all patients before the study (Malchow et al.1984
). Activity of the disease was determined by the
Crohn's Disease Activity Index (CDAI) (Best et al. 1979
).
At the beginning of the study, all patients were in an active phase of the disease defined by a CDAI >150. No patient had a history of chronic liver disease, diabetes mellitus, thyroid dysfunction or other acute or chronic diseases. None of the patients received corticosteroids or other immunosupressants during the study or within 3 mo before the study. At the time of the study, no patient had a body temperature >37.3°C or any signs of infection.
Nineteen age- and sex-matched healthy subjects served as controls. The
clinical data at baseline of controls, patients, and the subgroup of
patients subsequently receiving enteral nutrition are presented in
Table
1.
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Metabolic studies.
After an overnight fast, initial resting energy expenditure and
substrate oxidation rates were determined in controls and in all
patients by indirect calorimetry. Seven of the 32 patients were treated
with enteral nutrition as the sole therapy. In these patients, the
effect of enteral nutrition on energy and substrate metabolism was
studied by indirect calorimetry before (d 0) during (d 1, 7 and 14) and
12 h after ending enteral nutrition (d 15). Clinical data of these
seven patients are presented in Table 1
. Enteral nutrition was infused
continuously via a nasogastric tube and was started immediately after
indirect calorimetry on d 0. Enteral nutrition was started with an
infusion rate of 50 mL/h; increasing infusion rates were used to reach
the full dose of 100 mL/h (10.042 kJ/d) after 48 h. One patient
did not tolerate the full dose and was infused with 80 mL/h. A
peptide-based nutrition solution (Salvipeptid, Salvia, Germany) was
used; it contained 19 energy% protein, 27 energy% fat, and 54
energy% carbohydrates. The composition of the diet is presented in
Table
2.
Indirect calorimetry.
Patients and controls were studied on an outpatient status. They were asked not to perform unnecessary activities before entering the metabolic unit. Subjects were lying in bed in a supine position for at least 30 min before starting the measurements. They were instructed to lie quietly until measurements were completed.
Respiratory gas exchange was measured by computerized open-circuit
indirect calorimetry using a ventilated hood system (Deltatrac
Metabolic Monitor, Datex Instruments, Finland) as previously
described (Schneeweiss et al.1993
). Measurements were
done every minute, and the results were averaged over periods of 20
min. Calibrations were performed before and at the end of the
measurements. Urea nitrogen appearance rate (UNP) was calculated from
12-h urinary nitrogen excretion and changes in the body urea nitrogen
pool (Maroni et al. 1985
).
Body composition.
Lean body mass (LBM) was determined by anthropometry according to
Durnin and Womersley (1979). Triceps-, biceps-, subscapular- and
suprailiac-skinfolds were measured by a Lange caliper (Cambridge
Scientific, Cambridge, MD) and used to determine body density. Body fat
and LBM were calculated from density using Siri's equation
(Durin and Womersley 1974
).
Calculations.
REE and substrate oxidation rates were calculated from measured
VO2, VCO2 and UNP according
to Ferranini (1989)
and Frayn (1983)
. For this purpose, protein
oxidation was estimated from UNP (1 g urea nitrogen = 6.25 g
protein). UNP was calculated from urine urea nitrogen concentration and
urine volume per day:
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Substrate oxidation rates were expressed as a percentage of
total energy expenditure. Energy balances were calculated on d 7 and 14
in the seven patients receiving enteral nutrition, from 24-h energy
expenditure based on REE,taking into account an activity factor of 12%
of resting energy expenditure and a diet-induced thermogenesis of 6%
energy intake (Acheson et al. 1982
, Pollicino et al.1991
, Schneeweiss et al. 1991
).
Analytic measurements.
Urea nitrogen in urine was measured colorimetrically (Marsh et al. 1965
).
Statistical analysis.
All results are presented as means and SD. To compare data
between patients and controls, the Wilcoxon-test was used. The
relationship between REE and RQ, and UNP and total body mass was
assessed using least square regression (r). For testing the
relationship between CDAI and resting energy expenditure Spearman's
correlation coefficient (rs) adjusted for weight (partial
correlation coefficient) was calculated (Trampisch and Windeler 1997
). The effect of enteral nutrition on resting energy
expenditure and the proportion of energy expenditure derived from
carbohydrate, fat and protein oxidation were assessed by ANOVA with
repeated measurements, including contrasts between the different time
points.
Results were considered to be significant if P < 0.05. For numerical analysis, the SAS statistical package (SAS/STAT Version 6, SAS Institute, Cary, NC) was used.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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.
Measured REE expressed as kJ/min was not significantly different among
the groups (Table 3, Fig. 1
); a significant correlation between REE and total body mass
existed in patients (r = 0.75; P <
0.0001) and controls (r = 0.6; P <
0.01). The regression line for patients was on a slightly higher REE
level; however, the slopes of the lines and the y-intercepts
were not significantly different (Fig. 2
).
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The RQ was significantly lower in patients than in healthy controls
(Table 3)
, indicating a lower oxidation rate for carbohydrate and a
higher oxidation rate for fat in patients (Fig. 1)
. Due to the reduced
LBM (Table 2)
, UNP and protein oxidation rate (Fig. 1)
, calculated from
UNP, also were significantly lower in patients.
|
No change was observed in REE over the 15 d. UNP, RQ, and
non-protein RQ increased significantly on d 7 and 14 relative to d 0
and, except for the non-protein RQ, remained elevated even after
cessation of enteral nutrition (Table 4
). These changes were caused by a profound increase in carbohydrate
oxidation and protein oxidation, accompanied by a decrease in fat
oxidation (Fig.
3). All of these changes (except for carbohydrate oxidation rates)
were gradually reversed when enteral nutrition was discontinued on d 15
but remained significantly different from d 0 (Table 4)
. Energy
balances were positive on d 7 (+1.80 ± 0.68 kJ/min) and 14
(+1.87 ± 0.55 kJ/min). LBM (d 0: 38.5 ± 9.5 kg; d 14:
39.7 ± 9.1 kg) tended to increase (P = 0.07)
during the study.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). In contrast
to other studies, we did not find any influence of disease activity on
energy metabolism. Because our study was conducted in resting subjects,
no statement can be made on the status of energy metabolism during
physical activity.
To compare data from groups of patients with different body size and
body composition, metabolic parameters have to be normalized by the
active body mass (Ferranini 1989
). What should be used
as the denominator of metabolic rates has been discussed since the
early studies on energy metabolism performed by Lavoisier at the end of
the 18th century. Body weight, BSA, BMI, various
powers of body weight and LBM determined by different methods have all
been used to calculate "the" metabolical active tissue mass.
Azcue et al. (1997)
recently published a paper on energy
expenditure and body composition in children with Crohn's disease.
They normalized energy expenditure by total body weight and LBM,
calculated by bioelectrical impedance analysis, total body potassium
and the difference of total body water (measured with
H218O) and extracellular water
(determined with bromide space study). They found that the REE of
patients with Crohn's disease was not different from controls whether
expressed as calories per kilogram body weight or per kilogram LBM.
Royall et al. (1994a)
showed that determination of lean
body mass by bioelectric impedance analysis and by total body potassium
is of limited validity in malnourished patients. They found an
underestimation of free fat mass with wide scatter of values for
hydration of free fat mass when total body potassium was used, with
several values outside of the accepted biological limits. Data obtained
by bioelectric impedance analysis resulted in an overestimation of free
fat mass. The authors concluded that both methods and dual-energy X-ray
absorptiometry "should be proven to apply to a wider population
before it could be applied to all malnourished individuals"
(Royall et al. 1994a
).
Because there are no accurate methods available for measuring the
metabolically active body mass until now, we tried to overcome the
problems related to the determination of lean body mass by
normalization of metabolic data by comparing the slopes of the
regression lines between REE and LBM or total body mass. This approach
has been used in comparative physiology for years
(Schmidt-Nielsen 1984
). Calculating the regression
between total body weight and measured REE in both patients and healthy
controls, a significant correlation between these variables was found
in our study (patients: r = 0.75, P <
0.0001; controls: r = 0.6, P < 0.01).
The slopes were virtually identical. Because the regression lines
between body weight and REE were not different among the study groups,
the same conclusion concerning energy expenditure in Crohn's disease
would be expected, even if controls and patients were matched on the
basis of body weight and body composition. Our data are consistent with
the data of Azcue et al. (1997)
in children with Crohn's disease. They
also found that there was no difference in the slope of the relation
between REE and LBM.
The changes in substrate metabolism found in our patients resemble
those of starvation. In this condition, the RQ and urinary nitrogen
appearance rate are reduced, calculated oxidation rates for glucose and
protein are lowered and the oxidation rate for fat is elevated
(Cahill et al. 1966
). Factors such as a lowered food
intake due to anorexia and raised intestinal losses of nutrients may
lead to this alteration of substrate metabolism. These changes are
completely dependent on substrate availability. After only 1 d of
enteral nutrition, substrate oxidation rates were almost normalized in
our study. This normalization remained even after completion of enteral
nutrition and may reflect the availability of replenished glycogen
stores. Although the duration of enteral nutrition and the study period
were too short to show significant effects on body weight, body
composition and Crohn's disease activity, patients were in positive
energy balance. This has been linked to the efficiency of nutritional
therapy in patients with Crohn's disease (Royall et al. 1994b
).
It is surprising that we did not observe a decline in the metabolic rate in these patients who obviously were malnourished. The fact that energy expenditure is not lowered in Crohn's disease does not exclude the possibility that a reduction in the metabolic rate, caused by starvation, is masked by an elevation of energy expenditure by the inflammatory bowel disease; thus, no net effect on energy expenditure could be observed.
From our findings, we have to conclude that weight loss in patients
with Crohn's disease is not due to an elevation in energy expenditure,
but the consequence of malnutrition caused by anorexia, malabsorption
and increased intestinal losses (Gryboski 1993
,
Stokes 1992
).
In earlier studies, it was shown that enteral nutrition as well as
parenteral nutrition improved the nutritional status of patients with
Crohn's disease (Lochs et al.1991
, Pollicino et al. 1991
). Our data also support the importance of enteral
nutrition for these patients by demonstrating that infused substrates
are utilized.
Furthermore, energy balance was positive in our study (~1.8 kJ/min on
d 7 and 14). If we were to assume that the energy balance remains in
this range, over the 14-d feeding period, a weight gain of 1–2 kg,
depending on the nutrient stored, could be expected. However, we found
an increase in body weight of only 0.7 kg. The reason for this
discrepancy can be explained by stool losses, possible changes in
hydration status and the fact that we did not measure total energy
expenditure directly. Rather, we calculated it from REE, an activity
index of 12% of REE and a diet-induced thermogenesis of 6%
(Pollicino et al. 1991
).
In summary, patients with active Crohn's disease show changes in substrate oxidation similar to those in starvation, whereas energy expenditure is not altered as in catabolic diseases. Wasting, therefore, is a consequence of malnutrition but not of hypermetabolism in Crohn's disease. Refeeding normalized the observed changes in substrate metabolism, underlining the importance of enteral nutrition in this disease.
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FOOTNOTES |
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Manuscript received July 15, 1998. Initial review completed August 28, 1998. Revision accepted December 11, 1998.
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