Synopsis
A link between FODMAP malabsorption and stress has been suggested. Here, the effects of corticotrophin releasing factor (CRF) on fructose malabsorption are investigated in this randomised, placebo-controlled, crossover study in healthy volunteers. Background
Food plays a role in causing the
symptoms of irritable bowel syndrome (IBS). Poorly absorbed carbohydrates such
as fructose are known as FODMAPs (fermentable oligo-di-mono-saccharides and
polyhydric alcohols), and they tend to provoke symptoms of bloating, flatulence
and pain in IBS patients
1, 2.
Fructose increases the volume of free water in the small bowel
3. Any fructose not absorbed in the small bowel
enters the colon, leading to an increase in colon volume. IBS is also
associated with anxiety, and patients often report that its onset is associated
with stress. Stress increases the transit of meals through the small bowel
4, 5
and this may worsen the effects of malabsorption. Indeed, studies have
indicated that anxiety is a strong predictor of developing symptoms after a
FODMAPs meal
6 although the
mechanisms are unknown. Corticotrophin releasing factor (CRF) is capable of
activating the body’s stress response and injections of CRF have been shown to
reduce the volume of free water in the small bowel while increasing the volume
of the ascending colon
7. We hypothesised
that stress increases the action of fructose by accelerating its transit into
the colon, and we used CRF to test this.
Aim
To
investigate the effect of intravenous injection of CRF on fructose
malabsorption in healthy volunteers using MRI.
Methods
A randomised, placebo controlled,
cross-over study of CRF versus saline injection in healthy subjects, examining its
effect on the malabsorption of a 40 g fructose test meal and its transit
through the gut was assessed by serial MRI. 20 healthy volunteers (10 female, (age
23 ± 3 years, BMI 24.4 ± 3.4 kgm
-2) were randomised to take part.
They attended for scanning twice and were asked to fast from 20:00 hrs on the prior
day. MR scans were taken fasted, after which participants received an injection
of either CRF or saline followed by a fructose meal. Scans were then taken
every half hour for two hours, then hourly for another 2 hours. Images were
collected using a whole-body, research-dedicated, 1.5T MR scanner (Achieva,
Philips Medical System, Best, The Netherlands). The volume of water in the
small bowel was measured and analysed as described previously
8,
using a coronal single-shot turbo spin-echo sequence. This acquired 24 slices
in a single 24 second expiration breath hold (TR/TE = 8000/320 ms, 512x512
reconstructed matrix, voxel size 0.78x0.78x7 mm
3). A coronal
dual-echo gradient echo sequence was used to determine the volume of the
ascending colon
9. This sequence
allowed 24 slice collection of both in-phase and out-of-phase images simultaneously
in a single 15 second expiration breath hold (TR/TE1/TE2 = 157/2.30/4.60 ms,
256x256 reconstructed matrix, voxel size1.76x1.76x7 mm
3). Gastric
volumes were measured with a balanced gradient echo sequence (TR/TE = 2.98 /
1.49 ms, flip angle 80
o, 256 x 256 reconstructed matrix,
reconstructed in-plane resolution 1.56 x 1.56 x 5 mm
3, SENSE 2.0)
10,
acquiring 50 transverse slices in a 16.5 second breath hold.
Results
Small bowel water content (SBWC) increased
from baseline, peaking at 45 minutes after fructose ingestion. The area under
the curve (AUC) from -15 – 135 minutes postprandial was significantly lower
after CRF (48.5 ± 15 L) relative to the placebo (55.9 ± 19 L, P = 0.04), also demonstrated on the MR
images (Figure 1). Ascending colon volume (ACV) increased from baseline by 29%
after injection with CRF (Figure 2) compared to an increase of 12% after
injection with saline (P = 0.048).
Notable differences were observed between female and male volunteers: males showed
a significant increase in ACV) after CRF injection relative to the saline
injection (47%, P = 0.04), while
females registered a change of 8% between the two treatments (P = 0.7). Another difference between males and females
was the rate of gastric emptying; CRF significantly delayed gastric emptying in
female participants relative to the placebo (mean ± SD difference in AUC (t =
-15 – t = 135 min) 5.1 ± 6.1 L.min, P =
0.027, t test), but this delay was
not observed for the male participants (Figure 3).
Discussion/Conclusions
CRF is a chemical known to activate
the stress response. We used MRI to show that CRF decrease in small bowel water
volume compared to the placebo and increased ascending colon volumes,
consistent with it constricting the small bowel and increasing fructose malabsorption.
These observations help explain the increased sensitivity of some stressed
individuals to fructose malabsorption. Differences were seen between male and
female participants and the reasons for these differences require further
exploration.
Acknowledgements
We thank the participants for their involvement. We are also grateful
for the support of the NIHR Nottingham Digestive Diseases Biomedical Research
Unit. The views expressed are those of the authors and not necessarily those of
the NHS, the NIHR or the Department of Health.References
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