The Potential Role for Impaired Mucosal Integrity in the Generation of Esophageal Pain Using Capsaicin in Humans: An Explorative Study.

INTRODUCTION: Esophageal pain is mediated by sensory nerves, most importantly by the activation of the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor. TRPV1 is activated and sensitized by a broad range of pungent compounds, as well as inflammatory mediators and tissue irritants. Luminal stressors are suggested to impair the barrier function, which results in consequent activation of these sensory nerve terminals and pain. In this study, we investigated the effect of the perfusion of capsaicin, a TRPV1 agonist, on mucosal impedance and pain in asymptomatic volunteers. METHODS: Thirteen asymptomatic volunteers completed a single-blind, saline-controlled, randomized crossover study. Capsaicin or saline was perfused for 30 minutes in the distal esophagus. Visual analog scale pain intensity scores and intraluminal impedance indicating mucosal integrity were determined. Distal and proximal biopsies were obtained 10 minutes later to measure TRPV1 messenger RNA and TRPV1 immunopositivity, as well as the intercellular space area. RESULTS: Capsaicin perfusion resulted in significantly greater pain intensity (P = 0.047) and impaired recovery of the mucosal impedance compared with saline-treated controls (P = 0.027). Pain response was significantly associated with decreased mucosal impedance. Similar dynamics were seen in the proximal esophagus, but mucosal impedance recovered entirely to the preinfusion values there. There was a significant association between mucosal impedance and intercellular space width in the distal esophagus. TRPV1 transcription and expression were not significantly altered within this observation period. DISCUSSION: Esophageal capsaicin perfusion results in pain, which is likely to be explained by impaired mucosal impedance and defective restoration capacity in the distal esophagus.

Positive Health dialogue tool and value-based healthcare: a qualitative exploratory study during residents' outpatient consultations.

OBJECTIVE: To explore how residents experienced the application of the Positive Health dialogue tool (PH-tool) during outpatient consultations and its influence on the delivery of value-based healthcare (VBHC). DESIGN: Qualitative study using non-participant observations of outpatient consultations during which residents used the PH-tool, followed by longitudinal individual, semistructured interviews. To analyse the data from observations and interviews, observational form notes' summarisation and categorisation, and an iterative-inductive thematic approach was used. PARTICIPANTS: Eight residents-five from the ear, nose, and throat-department and three from the gastroenterology-hepatology-department-were selected through convenience sampling, accounting for 79 observations and 79 interviews. RESULTS: Residents had bivalent experiences with using the PH-tool. Residents discussed three main benefits: a gained insight into the individual patient's context and functioning, a changed dynamics in resident-patient communication, and an increased awareness regarding value in terms of patient-related outcomes and healthcare costs. Three barriers became apparent: doubts regarding the PH-tool's relevance and scope, boundaries of superspecialised medical professionals, and a lack of demarcation in clinical practice. CONCLUSION: The PH-tool use can be beneficial for residents during outpatient consultations with new patients and follow-up in cases of multidimensional problems, particularly in cases of chronic conditions and generalist care. In these situations, the tool yielded valuable patient information beyond physical health, helped foster patient engagement, and enabled tailoring the treatment plan to individual patients' needs. On the other hand, the PH-tool was not a good fit for simple problems, clearly demarcated help requests, periodic follow-up consultations, or verbose patients. In addition, it was not suitable for superspecialised care, because it yielded an abundance of general information. For particular patients and problems, using the PH-tool seems a promising strategy to increase VBHC delivery. Nevertheless, further research and detailing is needed to better align the PH-tool's broad intent and clinical practice.

Review on the Regional Effects of Gastrointestinal Luminal Stimulation on Appetite and Energy Intake: (Pre)clinical Observations.

Macronutrients in the gastrointestinal (GI) lumen are able to activate "intestinal brakes", feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this "intestinal brake" effect macronutrient specific? (3) is this "intestinal brake" effect maintained during repetitive activation? (4) can the "intestinal brake" effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the "intestinal brake" effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.

Control Crohn Safe with episodic adalimumab monotherapy as first-line treatment study (CoCroS): study protocol for a randomised controlled trial.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease with a heterogeneous clinical presentation, relapse rate and treatment response. At present, no markers are available to adequately predict disease course at diagnosis. To prevent overtreatment of patients with a relative mild disease course, a step-up approach starting with corticosteroids is usually applied. Timely introduction of potentially disease modifying drugs and tight control of mucosal inflammation are crucial to prevent disease-related complications in patients with a complex disease course. We hypothesise that episodic treatment with adalimumab monotherapy in combination with close monitoring after drug discontinuation improves long-term outcome and reduces drug-related side effects, while preventing overtreatment. METHODS AND ANALYSIS: In this pragmatic multicentre randomised controlled trial, newly diagnosed CD patients or CD patients with a flare, naïve to thiopurines and biologicals, will be included and randomised 1:1 to open-label episodic (ie, 24 weeks) adalimumab monotherapy or step-up care starting with corticosteroids. The primary outcome is the number of yearly quarters of corticosteroid free clinical (Monitor Inflammatory Bowel Disease At Home score ≤3) and biochemical (C reactive protein within normal range and faecal calprotectin ≤200 µg/g) remission at week 96. Secondary outcomes are total healthcare costs, cumulative corticosteroid dose, proportion of patients with endoscopic remission at week 24, corticosteroid-free clinical remission, time to remission and patient-reported outcome measures on quality of life, (work) disability and treatment adherence. Safety outcomes are drug-related and disease-related adverse events and disease progression on MRI-enterography at week 96. ETHICS AND DISSEMINATION: This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 21 August 2019 (METC18-076) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT03917303.

Absorption of nonheme iron during gastric acid suppression in patients with hereditary hemochromatosis and healthy controls.

Phlebotomies are performed in hereditary hemochromatosis (HH) to maintain normal iron concentrations. Proton-pump inhibitors (PPIs) can reduce the number of phlebotomies in patients with HH. However, in patients without HH, the iron concentrations do not appear to be compromised when using PPIs. Therefore, we aim to explain the differences in iron absorption between patients with and without HH. In 10 p.cysteine282tyrosine (p.C282Y) homozygous HH patients with normalized iron stores and 10 healthy control subjects (HCs), the iron parameters and hepcidin concentrations were determined before ingestion of a pharmacological dose of 50 mg iron [ferric iron (Fe3+)] polymaltose and hourly for 4 h afterward. This was repeated after 7 days of treatment with pantoprazole 40 mg once daily. Serum iron concentrations and transferrin saturation percentages dropped significantly during PPI use in the patients with HH, whereas no changes were observed in the HCs. Hepcidin concentrations were lower in the patients with HH compared with the HCs both before and during PPI use. In both groups, hepcidin levels did not significantly decrease during the treatment. Seven-day PPI use significantly reduces iron absorption in patients with HH but not in HCs. Changes in hepcidin concentrations could not explain these different PPI effects on iron absorption probably due to a small sample size.NEW & NOTEWORTHY This study confirms that lowering gastric acidity by proton pump inhibitors results in a reduction in iron absorption in patients with hemochromatosis and not in healthy control subjects. The presupposition that a decrease in hepcidin concentration in healthy control subjects in response to lowering gastric acidity can explain the difference in iron absorption between these groups could not be confirmed probably because of a small sample size.

Psychometric evaluation of an experience sampling method-based patient-reported outcome measure in functional dyspepsia.

BACKGROUND: Due to important biases, conventional end-of-day and end-of-week assessment methods of gastrointestinal symptoms in functional dyspepsia (FD) are considered suboptimal. Real-time symptom assessment based on the experience sampling method (ESM) could be a more accurate measurement method. This study aimed to evaluate validity and reliability of an ESM-based patient-reported outcome measure (PROM) for symptom assessment in FD. METHODS: Thirty-five patients with FD (25 female, mean age 44.7 years) completed the ESM-based PROM (a maximum of 10 random moments per day) and an end-of-day symptom diary for 7 consecutive days. On day 7, end-of-week questionnaires were completed including the Nepean Dyspepsia Index (NDI) and Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI-SYM). KEY RESULTS: Experience sampling method and corresponding end-of-day scores for gastrointestinal symptoms were significantly associated (ICCs range 0.770-0.917). However, end-of-day scores were significantly higher (Δ0.329-1.031) than mean ESM scores (p < 0.05). Comparing ESM with NDI and PAGI-SYM scores, correlations were weaker (Pearson's r range 0.467-0.846). Cronbach's α coefficient was good for upper gastrointestinal symptoms (α = 0.842). First half-week and second half-week scores showed very good consistency (ICCs range 0.913-0.975). CONCLUSION AND INFERENCES: Good validity and reliability of a novel ESM-based PROM for assessing gastrointestinal symptoms in FD patients was demonstrated. Moreover, this novel PROM allows to evaluate individual symptom patterns and can evaluate interactions between symptoms and environmental/contextual factors. ESM has the potential to increase patients' disease insight, provide tools for self-management, and improve shared decision making. Hence, this novel tool may aid in the transition toward personalized health care for FD patients.

Effects of gastrointestinal delivery of non-caloric tastants on energy intake: a systematic review and meta-analysis.

PURPOSE: Taste receptors are expressed throughout the gastrointestinal tract. The activation of post-oral taste receptors using tastants could provide a non-invasive treatment option in combating the obesity epidemic. The aim of this review was to examine the effect of post-oral delivery of non-caloric tastants on eating behavior reflected by primary outcome energy intake and secondary outcomes GI symptoms and perceptions and potential underlying mechanisms. This review was conducted according to the PRISMA guidelines for systematic reviews. METHODS: A systematic literature search of the Cochrane, PubMed, Embase, and Medline databases was performed. This systematic review and meta-analysis was registered in the PROSPERO database on 26 February 2020 (ID: CRD42020171182). Two researchers independently screened 11,912 articles and extracted information from 19 articles. If at least two studies investigated the effect of the same taste compound on primary outcome energy intake, a meta-analysis was performed to determine pooled effect sizes. RESULTS: Nineteen papers including healthy volunteers were included. In the 19 papers analyzed, effects of various tastants were investigated in healthy volunteers. Most extensively investigated were bitter tastants. The meta-analysis of effects of bitter tastants showed a significant reduction in energy intake of 54.62 kcal (95% CI - 78.54 to - 30.69, p = 0.0014). CONCLUSIONS: Bitter stimuli are most potent to influence eating behavior. Energy intake decreased after post-oral delivery of bitter tastants. This highlights the potential of a preventive role of bitter tastants in battling the obesity epidemic.

The effect of olive leaf extract on cardiovascular health markers: a randomized placebo-controlled clinical trial.

PURPOSE: Overweight and obesity are associated with many health problems, including cardiovascular disease (CVD). Evidence from previous studies has shown that extracts from olive leaves rich in olive phenolics are able to positively affect CVD risk factors, such as high blood pressure and dyslipidemia. The aim of this study was to investigate the effect of 8-week olive leaf extract (OLE) administration on blood lipid profiles in overweight/obese subjects with mildly elevated cholesterol levels. METHODS: In this randomized, double-blind, placebo-controlled study, 77 healthy adult overweight/obese subjects (aged 56 ± 10 years and BMI 29.0 ± 2.7 kg/m2) with total cholesterol levels of 5.0-8.0 mmol/L (5.9 ± 0.7 mmol/L) were randomly assigned to receive 500 mg of OLE (n = 39) or placebo (n = 38) for 8 weeks. In total, 74 subjects completed the entire study protocol. At baseline, after 4 weeks, and after 8 weeks of supplementation, blood lipid profiles, oxidized low-density lipoprotein (oxLDL), blood pressure, glucose, and insulin levels were assessed. In addition, liver function parameters were measured at baseline and after 8 weeks. RESULTS: OLE supplementation did not significantly affect blood lipid levels after 4 weeks or after 8 weeks compared to placebo (all p > 0.05). For oxLDL, blood pressure, glucose, and insulin levels and liver function parameters, also no statistically significant differences were found between the two intervention groups (all p > 0.05). CONCLUSIONS: Blood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels. TRIAL REGISTERED: The trial has been registered at ClinicalTrials.gov (NCT02990637).

Effect of oral or intragastric delivery of the bitter tastant quinine on food intake and appetite sensations: a randomised crossover trial.

Stimulation of gastrointestinal taste receptors affects eating behaviour. Intraduodenal infusion of tastants leads to increased satiation and reduced food intake, whereas intraileal infusion of tastants does not affect eating behaviour. Currently, it is unknown whether oral- or intragastric administration of tastants induces a larger effect on eating behaviour. This study investigated the effects of oral- and/or intragastric administration of quinine on food intake, appetite sensations and heart rate variability (HRV). In a blinded randomised crossover trial, thirty-two healthy volunteers participated in four interventions with a 1-week washout: oral placebo and intragastric placebo (OPGP), oral quinine and intragastric placebo (OQGP), oral placebo and intragastric quinine (OPGQ) and oral quinine and intragastric quinine (OQGQ). On test days, 150 min after a standardised breakfast, subjects ingested a capsule containing quinine or placebo and were sham-fed a mixture of quinine or placebo orally. At 50 min after intervention, subjects received an ad libitum meal to measure food intake. Visual analogue scales for appetite sensations were collected, and HRV measurements were performed at regular intervals. Oral and/or intragastric delivery of the bitter tastant quinine did not affect food intake (OPGP: 3273·6 (sem 131·8) kJ, OQGP: 3072·7 (sem 132·2) kJ, OPGQ: 3289·0 (sem 132·6) kJ and OQGQ: 3204·1 (sem 133·1) kJ, P = 0·069). Desire to eat and hunger decreased after OQGP and OPGQ compared with OPGP (P < 0·001 and P < 0·05, respectively), whereas satiation, fullness and HRV did not differ between interventions. In conclusion, sole oral sham feeding with and sole intragastric delivery of quinine decreased desire to eat and hunger, without affecting food intake, satiation, fullness or HRV.

The Intestinal Fate of Citrus Flavanones and Their Effects on Gastrointestinal Health.

Citrus flavanones, with hesperidin and naringin as the most abundant representatives, have various beneficial effects, including anti-oxidative and anti-inflammatory activities. Evidence also indicates that they may impact the intestinal microbiome and are metabolized by the microbiota as well, thereby affecting their bioavailability. In this review, we provide an overview on the current evidence on the intestinal fate of hesperidin and naringin, their interaction with the gut microbiota, and their effects on intestinal barrier function and intestinal inflammation. These topics will be discussed as they may contribute to gastrointestinal health in various diseases. Evidence shows that hesperidin and naringin are metabolized by intestinal bacteria, mainly in the (proximal) colon, resulting in the formation of their aglycones hesperetin and naringenin and various smaller phenolics. Studies have also shown that citrus flavanones and their metabolites are able to influence the microbiota composition and activity and exert beneficial effects on intestinal barrier function and gastrointestinal inflammation. Although the exact underlying mechanisms of action are not completely clear and more research in human subjects is needed, evidence so far suggests that citrus flavanones as well as their metabolites have the potential to contribute to improved gastrointestinal function and health.

Intraintestinal Delivery of Tastants Using a Naso-Duodenal-Ileal Catheter Does Not Influence Food Intake or Satiety.

Intraduodenal activity of taste receptors reduces food intake. Taste receptors are expressed throughout the entire gastrointestinal tract. Currently, there are no data available on the effects of distal taste receptor activation. In this study, we investigate the effect of intraduodenal and/or intraileal activation of taste receptors on food intake and satiety. In a single-blind randomized crossover trial, fourteen participants were intubated with a naso-duodenal-ileal catheter and received four infusion regimens: duodenal placebo and ileal placebo (DPIP), duodenal tastants and ileal placebo (DTIP), duodenal placebo and ileal tastants (DPIT), duodenal tastants and ileal tastants (DTIT). Fifteen minutes after cessation of infusion, subjects received an ad libitum meal to measure food intake. Visual analog scale scores for satiety feelings were collected at regular intervals. No differences in food intake were observed between the various interventions (DPIP: 786.6 ± 79.2 Kcal, DTIP: 803.3 ± 69.0 Kcal, DPIT: 814.7 ± 77.3 Kcal, DTIT: 834.8 ± 59.2 Kcal, p = 0.59). No differences in satiety feelings were observed. Intestinal infusion of tastants using a naso-duodenal-ileal catheter did not influence food intake or satiety feelings. Possibly, the burden of the four-day naso-duodenal-ileal intubation masked a small effect that tastants might have on food intake and satiety.

The Effect of an Encapsulated Nutrient Mixture on Food Intake and Satiety: A Double-Blind Randomized Cross-Over Proof of Concept Study.

Activation of the intestinal brake by infusing nutrients into the distal small intestine with catheters inhibits food intake and enhances satiety. Encapsulation of macronutrients, which protects against digestion in the proximal gastrointestinal tract, can be a non-invasive alternative to activate this brake. In this study, we investigate the effect of oral ingestion of an encapsulated casein and sucrose mixture (active) targeting the distal small intestine versus a control product designed to be released in the stomach on food intake, satiety, and plasma glucose concentrations. Fifty-nine volunteers received the active and control product on two separate test days. Food intake was determined during an ad libitum meal 90 min after ingestion of the test product. Visual analogue scale scores for satiety and blood samples for glucose analysis were collected at regular intervals. Ingestion of the active product decreased food intake compared to the control product (655 kcal compared with 699 kcal, respectively, p < 0.05). The area under the curve (AUC) for hunger was decreased (p < 0.05) and AUC for satiety was increased (p < 0.01) after ingestion of the active product compared to the control product. Ingestion of an encapsulated protein-carbohydrate mixture resulted in inhibition of food intake compared to a non-encapsulated control product.

Functional urological disorders: a sensitized defence response in the bladder-gut-brain axis.

Functional urological and gastrointestinal disorders are interrelated and characterized by a chronic course and considerable treatment resistance. Urological disorders associated with a sizeable functional effect include overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Poor treatment outcomes might be attributable to untreated underlying psychological and psychiatric disorders, as the co-occurrence of functional urological and gastrointestinal disorders with mood and anxiety disorders is common. The hypothetical bladder-gut-brain axis (BGBA) is a useful framework under which this interaction can be studied, suggesting that functional disorders represent a sensitized response to earlier threats such as childhood adversity or previous traumatic events, resulting in perceived emotional and bodily distress - the symptoms of functional disorders. Psychological and physical stress pathways might contribute to such alarm falsification, and neuroticism could be a risk factor for the co-occurrence of functional disorders and affective conditions. Additionally, physical threat - either from external sources or internal sources such as infection - might contribute to alarm falsification by influencing body-brain crosstalk on homeostasis and, therefore, affecting mood, cognition, and behaviour. Multidisciplinary research and an integrated care approach is, therefore, required to further elucidate and remediate functional urological and gastrointestinal polymorphic phenotypes.

Effect of Vagus Nerve Injury on the Outcome of Antireflux Surgery: An Extensive Literature Review.

BACKGROUND: Vagus nerve injury (VNI) is a feared complication of antireflux surgery (ARS). The impact of VNI on the functional outcomes of ARS has not yet been evaluated systematically. The aim of this review was to evaluate the impact of VNI on functional and clinical outcome of ARS. METHODS: A systematic search was performed until March 2015, using the following online databases: MEDLINE, Embase and the Cochrane Register of Controlled Clinical Trials. Eight studies remained available for assessment. Articles were divided into 2 groups: (a) one with unintended, accidental VNI and (b) one group comparing ARS with and without intended vagotomy. RESULTS: The prevalence of unintended, accidental VNI ranged from 10 to 42% after ARS. No clear differences were seen in outcome for reflux control between the VNI and vagus nerve intact group. A higher prevalence of diarrhea, nausea and vomiting was observed in the VNI group. CONCLUSION: VNI is a feared but neglected complication of ARS. Larger prospective studies that objectively assess vagus nerve integrity before and after ARS are needed.

Effect of Vagus Nerve Integrity on Short and Long-Term Efficacy of Antireflux Surgery.

OBJECTIVES: Vagus nerve injury is a feared complication of antireflux surgery (ARS) that may negatively affect reflux control. The aim of the present prospective study was to evaluate short-term and long-term impact of vagus nerve injury, evaluated by pancreatic polypeptide response to insulin-induced hypoglycemia (PP-IH), on the outcome of ARS. METHODS: In the period from 1990 until 2000, 125 patients with gastroesophageal reflux disease (GERD) underwent ARS at a single center. Before and 6 months after surgery, vagus nerve integrity testing (PP-IH), 24-h pH-monitoring, gastric emptying, and reflux-associated symptoms were evaluated. In 2014, 14-25 years after surgery, 110 patients were contacted again for evaluation of long-term symptomatic outcome using two validated questionnaires (Gastrointestinal Symptom Rating Scale (GSRS) and GERD-Health Related Quality of Life (HRQL)). RESULTS: Short-term follow-up: vagus nerve injury (PP peak ≤47 pmol/l) was observed in 23 patients (18%) 6 months after fundoplication. In both groups, a comparable decrease in reflux parameters and symptoms was observed at 6-month follow-up. Postoperative gastric emptying was significantly delayed in the vagus nerve injury group compared with the vagus nerve intact group. Long-term follow-up: patients with vagus nerve injury showed significantly less effective reflux control and a higher re-operation rate. CONCLUSIONS: Vagus nerve injury occurs in up to 20% of patients after ARS. Reflux control 6 months after surgery was not affected by vagus nerve injury. However, long-term follow-up showed a negative effect on reflux symptom control and re-operation rate in patients with vagus nerve injury.

Gastrointestinal Nutrient Infusion Site and Eating Behavior: Evidence for A Proximal to Distal Gradient within the Small Intestine?

The rapidly increasing prevalence of overweight and obesity demands new strategies focusing on prevention and treatment of this significant health care problem. In the search for new and effective therapeutic modalities for overweight subjects, the gastrointestinal (GI) tract is increasingly considered as an attractive target for medical and food-based strategies. The entry of nutrients into the small intestine activates so-called intestinal "brakes", negative feedback mechanisms that influence not only functions of more proximal parts of the GI tract but also satiety and food intake. Recent evidence suggests that all three macronutrients (protein, fat, and carbohydrates) are able to activate the intestinal brake, although to a different extent and by different mechanisms of action. This review provides a detailed overview of the current evidence for intestinal brake activation of the three macronutrients and their effects on GI function, satiety, and food intake. In addition, these effects appear to depend on region and length of infusion in the small intestine. A recommendation for a therapeutic approach is provided, based on the observed differences between intestinal brake activation.

Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones.

BACKGROUND: Capsaicin, which is the major pungent principle in chili peppers, is able to induce satiety and reduce caloric intake. The exact mechanism behind this satiating effect is still unknown. We hypothesized that capsaicin induces satiety through the release of gastrointestinal peptides, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), from enteroendocrine cells in the small intestine. OBJECTIVE: We investigate the effects of an intraduodenal capsaicin infusion (1.5 mg pure capsaicin) in healthy volunteers on hunger, satiety, and gastrointestinal symptoms and the release of GLP-1 and PYY. DESIGN: Thirteen participants (7 women) [mean ± SEM age: 21.5 ± 0.6 y; body mass index (in kg/m(2)): 22.8 ± 0.6] participated in this single-blind, randomized, placebo-controlled crossover study with 2 different treatments. During test days, an intraduodenal infusion of either capsaicin or a placebo (physiologic saline) was performed with the use of a nasoduodenal catheter over a period of 30 min. Visual analog scale scores were used to measure hunger, satiety, and gastrointestinal symptoms. Blood samples were drawn at regular intervals for GLP-1 and PYY. Gallbladder volumes were measured with the use of real-time ultrasonography. RESULTS: The intraduodenal capsaicin infusion significantly increased satiety (P-treatment effect < 0.05) but also resulted in an increase in the gastrointestinal symptoms pain (P-treatment × time interaction < 0.0005), burning sensation (P-treatment × time interaction < 0.0001), nausea (P-treatment × time interaction < 0.05), and bloating (P-treatment × time interaction < 0.001) compared with the effects of the placebo infusion. Satiety scores had a positive correlation with all gastrointestinal symptoms. No differences in GLP-1 and PYY concentrations and gallbladder volumes were observed after the capsaicin infusion compared with after the placebo infusion. CONCLUSIONS: An intraduodenal infusion of capsaicin significantly increases satiety but does not affect plasma concentrations of GLP-1 and PYY. Rather, the effect on satiety seems related to gastrointestinal stress as shown by the associations with pain, burning sensation, nausea, and bloating scores. This trial was registered at clinicaltrials.gov as NCT01667523.