[show abstract][hide abstract] ABSTRACT: Irritable bowel syndrome (IBS) patients suffer from visceral hypersensitivity and show increased activity in the brain emotional arousal network following a rectal stimulus, compared with controls. Serotonergic activity can be decreased by acute tryptophan depletion (ATD), which increases visceral perception and also increases activity in the brain's emotional arousal network during rectal stimulation. Treatment with a serotonin reuptake inhibitor such as citalopram is effective in some IBS patients. Hence, serotonergic modulation alters visceral perception. However, it is not clear whether serotonergic modulation alters rectal motor function.
The aims of the study were to evaluate the effect of the administration of ATD and citalopram on rectal motor function in diarrhea-predominant IBS (d-IBS) patients and controls using a barostat procedure.
Following a randomized, double-blind placebo-controlled crossover design, an ATD and citalopram experiment was conducted. Fourteen d-IBS patients and 14 healthy, matched (age, sex, BMI) controls participated. Rectal volume (RV), adaptive relaxation (RAR), and compliance (RC) were determined using a barostat procedure.
d-IBS patients showed significantly decreased RV (P<0.04), RAR (P<0.03), and RC (P=0.05) compared with the controls. ATD and citalopram did not influence RV, RAR, or RC significantly (all P's>0.1).
d-IBS patients have disturbed rectal pressure-volume relations. Visceral perception in IBS is associated with both increased activity in the brain's emotional arousal network and decreased RC. Acutely decreasing or increasing serotonergic activity does not affect these characteristics in d-IBS patients or healthy controls. The pathophysiology in d-IBS contains both a rectal motor component and a central neuropsychologic component.
European journal of gastroenterology & hepatology 08/2012; 24(11):1259-65. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD.
12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years).
In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C.
The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.
Gut 03/2011; 60(9):1196-203. · 10.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is a growing interest in highly fermentable dietary fibers having the potential to reduce risks of disease through the production of short-chain fatty acids (SCFA). Recently a digestion-resistant retrograded maltodextrin (RRM), classified as type 3 resistant starch was developed. Systematic work to determine its molecular and physiological properties was carried out to determine (1) the fraction resistant to digestion in vitro and in vivo, (2) its postconsumption effect on blood glucose in healthy volunteers, and (3) its in vitro fermentation pattern, at different ages, by use of pooled fresh human fecal inoculum. RESULTS: The digestion resistant fraction obtained in vivo from ileostomy patients (59.4%) is similar to that obtained by the AOAC method for measuring retrograded resistant starch (59.7%). The relative glycemic response after consumption of 50 g of RRM was 58.5% compared to glucose set as 100%. When exposed to colonic microbiota, in vitro obtained indigestible fractions behave similarly to those obtained in vivo in ileostomy patients. Fermentation of RRM and production of butyric acid is negligible during the first months of life but develops subsequently during weaning. In adults, RRM fermentation results in a high yield of SCFA, with butyrate representing 21-31 mol % of total SCFA. The high yield of SCFA during colonic fermentation, observed from weaning age on, as well as the potential to help reduce glycemic load may be of benefit to a number of health-related functions in the host. Further study on clear clinical end points is warranted.
Journal of Agricultural and Food Chemistry 03/2007; 55(4):1574-81. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastrointestinal (GI) complaints are frequently experienced during running. Sports drinks to prevent dehydration and hypoglycemia during exercise are generally used. The aim was to investigate the effect of 3 different drinks on GI complaints and performance during competitive running in a controlled field study. Ninety-eight well-trained subjects (90 M, 8 F, age 41 +/- 8 y) performed a competitive 18-km run three times within 8 days. The study was a controlled, standardized field experiment following a randomized, crossover design. Three different drinks were compared: water, a sports drink (CES), and a sports drink with added 150 mg/l caffeine (CAF). The incidence of GI complaints and the effect of the drinks on performance was studied. Each subject consumed 4 times 150 ml as follows: at the start, after 4.5 km, 9 km, and 13.5 km. Fluid intake was controlled. Incidence and intensity of GI complaints during the run were determined using a 10 points scale questionnaire. There were no significant differences in performance between the 3 drinks. Run time (18 km, mean +/- SD): WAT 1 : 18 : 03 +/- 08 : 30, CES 1 : 18 : 23 +/- 08 : 47, CAF 1 : 18 : 03 +/- 08 : 42. The use of carbohydrate-containing sports drinks led to higher incidences of all types of GI complaints compared to water. Significant differences (p < 0.05) were reached for flatulence; incidence: WAT 17.9 %, CES 28.6 %, CAF 30.6 %, and reflux; incidence: WAT 55.7 %, CES 78.6 %, CAF 72.5 %. There were no significant differences in intensity of the GI complaints. Addition of caffeine to CES had no effect on GI complaints, compared to CES alone. We conclude that sports drinks used during an 18-km run in cool environmental conditions do not support the performance better than mineral water. The use of sports drinks during an 18-km run leads to a higher incidence of both upper and lower GI complaints compared to water. Addition of caffeine to the sports drink has no effect on either running performance or GI complaints.
International Journal of Sports Medicine 05/2005; 26(4):281-5. · 2.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Serotonin, a key denominator of the brain-gut axis, is involved in the regulation of gastrointestinal motility, secretion, and perception as well as cognition and mood.
To assess the effects of an acutely lowered serotonin synthesis, using the acute tryptophan depletion (ATD) method, on visceral perception, affective memory performance, and mood in diarrhoea predominant irritable bowel syndrome patients (d-IBS) and controls.
In a randomised, double blind, crossover design, 14 d-IBS patients and fourteen matched controls were studied under ATD and placebo conditions, respectively. Perception of urge and pain was scored during rectal distensions. Affective memory performance, mood, and biochemical parameters of serotonergic metabolism were simultaneously assessed.
ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) mumol/l) and 5-hydroxyindole acetic acid concentrations (29.9 (1.0) v 15.8 (0.6) nmol/l). ATD was associated with significantly increased urge scores specifically in the lower pressure range and overall increased pain scores. ATD significantly lowered the perceptual threshold for first perception compared with placebo (patients 10.6 (1.2) v 13.6 (0.8) mm Hg, controls 12.6 (1.3) v 15.7 (1.2) mm Hg) but not for maximal tolerable discomfort (patients 50.5 (3.6) v 51.6 (3.3) mm Hg, controls 50.9 (3.3) v 48.8 (2.9) mm Hg). ATD induced a significant shift in affective memory bias towards preferential loss of positive material but no significant changes in mood. ATD did not differentially affect the patient or control group.
We have provided evidence that serotonergic modulation by ATD affects both visceral perception as well as cognition in d-IBS and controls. Simultaneous measurement of brain and gut function and the application of ATD contribute to the elucidation of the complex pathophysiology of IBS.
Gut 01/2005; 53(12):1794-800. · 10.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Some athletes suffer from exercise-induced gastrointestinal (GI) disturbances. We developed a profile of GI parameters in 10 symptomatic and 10 asymptomatic athletes both at rest and during exercise. Exercise included 90 min of cycling and running at 70% of maximal power. We measured oesophageal motility, gastro-oesophageal reflux, gastric emptying, orocaecal transit time (OCTT), intestinal permeability and intestinal glucose absorption. During cycling the number and duration of refluxes were increased, whereas gastric emptying showed no differences between rest, cycling and running. The OCTT was increased in the running trial, compared to rest (P=0.005). Also, intestinal permeability was higher in the running trial, compared to rest (P=0.008). There were no differences in intestinal glucose absorption between rest and exercise. Compared with asymptomatic athletes the symptomatic subjects had a higher intestinal permeability (P=0.001), more reflux episodes (P=0.03) and a longer duration of reflux (P<0.05) during cycling. No differences were observed at rest. In conclusion, there is no difference in GI profile between symptomatic and asymptomatic athletes at rest. During exercise, symptomatic subjects have a longer OCTT and a higher intestinal permeability, which is more pronounced during running than during cycling.
[show abstract][hide abstract] ABSTRACT: Serotonin (5-HT) is an important neurotransmitter involved in the brain-gut axis. It is possible to lower the 5-HT level in the body by means of a nutritional intervention using an amino acid mixture; the acute tryptophan depletion (ATD) method. We studied the effect of ATD on gastric emptying in healthy females, who received both ATD and placebo in a random order. Gastric emptying was measured using the [(13)C]octanoic acid breath test. The present data demonstrate significant differences in both gastric emptying and lag phase (Tlag) between the ATD and placebo experiment. Eight out of ten subjects showed a delayed gastric emptying in the ATD experiment. Both the gastric half-emptying time (T1/2) and the Tlag were significantly higher in the ATD experiment. T1/2 in the ATD experiment was 137.2 (range 76.2-634.8) min; T1/2 for the placebo experiment was 98.5 (range 63.7-168.8) min (P=0.028). Tlag in the ATD experiment was 83.7 (range 45.1-356.2) min; Tlag for the placebo experiment was 56.9 (range 23.2-101.2) min (P=0.007). We conclude that lowering the 5-HT level in the body using the ATD method leads to a significantly delayed gastric emptying of a solid meal. Nutritional manipulation of the serotonergic system in healthy volunteers may lead to alterations in gastrointestinal motility.
British Journal Of Nutrition 04/2004; 91(3):351-5. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome.
To analyse, systematically, randomized controlled trials studying the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome, in order to elucidate baseline irritable bowel syndrome symptomatology and possible differential effects of serotonergic modulation on this symptomatology.
A standardized qualitative analysis was performed of studies investigating the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome using a blind review approach. The studies were ranked according to their total quality score (maximum 100 points).
Eleven studies fulfilled the entry criteria, six of which scored above 55 points. An association between gastroenterological and psychiatric changes was present in five of the six studies.
The results strengthen the serotonergic association between gastroenterological and psychiatric symptoms. Adjusted guidelines for combined gastrointestinal and psychiatric assessments are recommended in order to further elucidate the serotonergic interaction between gastrointestinal and psychiatric symptoms.
[show abstract][hide abstract] ABSTRACT: The development of the sports food market and industrial involvement have led to numerous nutritional studies to define the type of nutrients that are most suited to support energy metabolism, fluid balance and muscle function. The key question in many of these studies was: 'Does the product lead to a significant product/consumer benefit that can be used as a claim on the package?' New methods and techniques have been developed, partly with sponsorship of the food industry, with the goal of measuring the effects of specific nutrients and supplements on athletic performance and metabolism. In line with this development, a wide variety of supplements and sports foods/drinks labelled with various performance or health benefit statements have been launched on the sports nutrition market. Although a variety of products have been tested clinically, there are also many products on the market with benefit claims that cannot be supported by sound nutritional and sports physiological science. The current short review highlights some of the methods and biomarkers that are used to substantiate product/consumer benefit claims for foods and drinks that are marketed as functional foods for athletes.
British Journal Of Nutrition 12/2002; 88 Suppl 2:S177-86. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is no consensus about the effect of guar gum supplementation on gastrointestinal transit. It has been suggested that guar gum slows gastric emptying and intestinal transit, thus inducing an increased feeling of satiety.
To investigate whether addition of guar gum to a semisolid meal affects gastrointestinal transit.
Eight male subjects were randomly studied four times. They consumed a standard semisolid test meal containing either 0 g, 2.5 g, 3.5 g, or 4.5 g of guar gum. The test meals contained 1 mCi 99mTc-hepatate for scintigraphy and 5 g lactulose for the H2-breath test. Scintigraphic scanning was performed for at least two hours, and gastric half-emptying time (T1/2) was calculated. Breath samples were collected at 15 minute intervals and analyzed for H2-enrichment. The orocecal transit time (OCTT) was then determined. A parameter of intestinal transit (PIT) was obtained by subtracting the T1/2 from the OCTT.
There were no significant differences (in minutes) between the different tests in both T1/2 (0 g, t = 88.2 +/- 11, 2.5 g, t = 83.3 +/- 11.9, 3.5 g, t = 83.3 +/- 13.6, 4.5 g, t = 72.4 +/- 7.2, p = 0.86) and PIT (0 g, t = 149.9 +/- 26.6, 2.5 g, t = 145.5 +/- 25.6, t = 3.5 g, t = 175.3 +/- 17.6, t = 4.5 g, t = 152.6 +/- 22.4, p = 0.52).
Addition of guar gum to a semisolid meal up to a dosage of 4.5 g does not affect gastrointestinal transit. Other mechanisms than gastrointestinal motility are involved in a possible satiating effect of guar gum supplementation.
Journal of the American College of Nutrition 03/2001; 20(1):87-91. · 1.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dehydration leads to the aggravation of gastrointestinal (GI) complaints during exercise. The aim of this study was to examine the effect of dehydration on various GI parameters during strenuous exercise. Ten healthy well-trained men were investigated in dehydrated and in euhydrated conditions. Dehydration took place before the experiments using a dehydration regimen in a sauna leading to a 3% loss of body mass. Each experiment consisted of 1 h pre-exercise rest, 1.5 h cycling at 70% maximal exercise intensity, and 3.5 h post-exercise rest. During cycling, liquid gastric emptying (GE), orocaecal transit time (OCTT) and intestinal permeability and glucose absorption were measured. The GI-symptoms were scored using a questionnaire. Body temperature, plasma volume and vasopressin were measured before and after cycling. The GE was significantly slower during dehydration [median time to peak 13C enrichment in the breath sample (13C-TTP) 23.6 min, range 13.7-50.0 min, P = 0.02] than in the control situation (median 13C-TTP 17.1 min, range 9.8-38.4 min). The OCTT was unchanged (median 173 min, range 98-263 min compared to median 128 min, range 98-195 min, P = 0.18). Dehydration did not change intestinal permeability, glucose absorption, plasma volume, rectal temperature or plasma vasopressin concentration. In the dehydration experiment, exercise induced a significant increase in nausea (P = 0.01) and epigastric cramps (P = 0.05), in contrast to the control situation. In both experiments, exercise led to a significant increase in rectal temperature and plasma vasopressin concentration, and a significant decrease in plasma volume. The increase in plasma vasopressin concentration was significantly higher in the dehydration experiment (P = 0.015). No significant differences in either the post-exercise rectal temperatures or in plasma volumes was observed. The difference in GE between the two experiments was significantly correlated with the difference in nausea score (r = 0.87, P = 0.002). We concluded that dehydration leads to a delayed GE but not to differences in OCTT, intestinal permeability or glucose uptake during intense cycling. The delay in GE is significantly associated with an increase in exercise-induced nausea.