Article

The effects of capsaicin on reflux, gastric emptying and dyspepsia

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Abstract

To evaluate capsaicin's effects on heartburn, dyspepsia, gastric acidity and emptying, and gastro-oesophageal reflux, and to test the hypothesis that capsaicin induces heartburn and exacerbates symptoms by sensitizing the oesophagus. Eleven heartburn sufferers underwent two separate pH monitoring sessions and assessments of gastric emptying (13C-octanoic acid breath test), heartburn and dyspepsia (100 mm VAS) after a non-irritant meal. The meal consisted of a sausage biscuit with egg, cheese and 30 g raw onion, 8 oz chocolate milk and a peppermint patty. Thirty minutes prior to meal consumption, subjects were administered a placebo capsule. On visit 1, subjects consumed the meal containing 100 microl 13C-octanoic acid cooked in the egg, over 15 min. On visit 2, subjects consumed the meal plus 5 mg capsaicin in gelatin capsules. Oesophageal and gastric pH profiles and gastric emptying were not different between meals. Capsaicin did not alter mean heartburn and dyspepsia scores (P > 0.05), but significantly decreased time to peak heartburn (120 min vs. 247 min; P < 0.003). Time to peak dyspepsia was not altered by capsaicin (P > 0.05). Capsaicin enhances noxious postprandial heartburn, presumably by direct effects on sensory neurons.

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... It can stimulate the transient receptor potential vanilloid 1 (TRPV1) receptors in the gastrointestinal tract and can produce pain and a burning sensation in humans [1][2][3]. Abdominal burning, abdominal pain, and heartburn often develop after chili ingestion in patients with peptic ulcer disease, functional dyspepsia, and gastroesophageal reflux disease (GERD) [4,5], suggesting the role of capsaicin-sensitive nociceptive pathways in the development of symptoms in these patients. Although the effect of chili on gastrointestinal sensation has been well demonstrated, the effect of chili on gastric motor function has not been well explored. ...
... Although the effect of chili on gastrointestinal sensation has been well demonstrated, the effect of chili on gastric motor function has not been well explored. Previous studies demonstrated that ingestion of a meal with capsaicin in a capsule delay gastric emptying [5][6][7][8] but increase small bowel transit time in humans [6,7]. Acute administration of red pepper containing capsaicin in the stomach has been reported to decrease proximal gastric tone, inhibit phasic contractility of the proximal stomach, and increase sensitivity to proximal gastric distension in healthy volunteers [9]. ...
... The finding that chili could induce abdominal burning symptoms in NERD patients but not in healthy volunteers suggests that the upper gut of a NERD patient is hypersensitive to chili. Previous studies have shown that chili or capsaicin can induce abdominal burning, abdominal pain, and heartburn via c-fiber and TRPV1 receptors [19][20][21] and that chili ingestion can aggravate these symptoms in GERD patients [4,5]. Moreover, our study also has shown a significant decrease in early satiety symptom scores in NERD patients after a meal with chili. ...
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The effects of chili on gastric accommodation (GA) in gastroesophageal reflux disease (GERD) patients have not been explored. Methods: In total, 15 healthy volunteers (HV) and 15 pH-positive non-erosive GERD (NERD) patients underwent single-photon emission computed tomography after ingesting 2 g of chili or placebo in capsules in a randomized double-blind crossover fashion with a one-week washout period. GA was the maximal postprandial gastric volume (GV) after 250 mL of Ensure® minus the fasting GV. Upper gastrointestinal symptoms were evaluated by using a visual analog scale. Results: NERD patients but not HV had significantly greater GA after chili compared to a placebo (451 ± 89 vs. 375 ± 81 mL, p < 0.05). After chili, the postprandial GVs at 10, 20, and 30 min in NERD patients were significantly greater than HV (10 min, 600 ± 73 vs. 526 ± 70 mL; 20 min, 576 ± 81 vs. 492 ± 78 mL; 30 min, 532 ± 81 vs. 466 ± 86 mL, all p < 0.05). In NERD, chili was associated with significantly less satiety, more severe abdominal burning (p < 0.05), and a trend of more severe heartburn (p = 0.06) compared to the placebo. In HV, postprandial symptoms after chili and placebo ingestion were similar (p > 0.05). Conclusions: Chili enhanced GA in NERD patients but not in HV. This suggests that the modulation of GA in NERD is abnormal and likely involves transient receptor potential vanilloid 1 (TRPV1) sensitive pathways.
... The most common toxic effect of capsaicin ingestion is gastric distress [46]. However, capsaicin has also been studied for its potential therapeutic applicability in relieving gastric reflux-related symptoms due to its hypersensitizing and pain-relieving effects [4,47]. Esophageal infusion with a tabasco sauce suspension (0.84 mg capsaicin) increased the sensitivity to distension-induced secondary peristalsis, although the effect of capsaicin was reduced upon repeated exposure in both patients with gastroesophageal reflux disease (GERD) [48] and healthy volunteers [49]. ...
... However, the same study also reported that chili could induce abdominal burning symptoms in NERD patients but not in healthy volunteers [50]. Additionally, capsaicin (5 mg) did not affect either gastric emptying or dyspepsia, but it increased postprandial abdominal pain in patients with heartburn [47]. In healthy individuals, 3 g of cascabel chili (2.64 mg capsaicin) but not ancho chili (1.46 mg capsaicin) significantly increased the number of reflux episodes and the percentage of time in which the pH in the esophagus is below 4 [51]. ...
... In healthy individuals, 3 g of cascabel chili (2.64 mg capsaicin) but not ancho chili (1.46 mg capsaicin) significantly increased the number of reflux episodes and the percentage of time in which the pH in the esophagus is below 4 [51]. Therefore, studies have indicated that even low doses of capsaicin (<5 mg) can cause acute abdominal pain in healthy individuals [51] and aggravate abdominal burning symptoms or reflux in GERD patients and individuals prone to heartburn [47,50]. However, these studies that investigated the acute effects of capsaicin were relatively small and employed various capsaicin treatment regimens, making it difficult to compare them. ...
Article
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The consumption of capsaicinoids, the active components in chili peppers, has been associated with both positive and negative health effects, and the level of capsaicinoid exposure may be an important determinant. Dietary capsaicinoid exposure was estimated using a previously developed database for capsaicinoid content and a 24-h dietary recall dataset obtained from the Korea National Health and Nutrition Examination Survey. The estimated consumption level was evaluated to determine its potential effects on weight reduction and gastrointestinal distress. The estimated daily mean capsaicinoid intake was 3.25 mg (2.17 mg capsaicin), and most Koreans consumed 1–30 mg of capsaicinoids (0.67–20 mg capsaicin) in a day. No adverse effect of capsaicin consumption was reported other than abdominal pain. For long-term repeated consumption, 30 mg may be the maximum tolerable dose. However, the effects on body weight or energy balance were inconsistent in 4–12 week clinical studies conducted with various capsaicin doses (2–135 mg), which was likely due to the complex interplay between capsaicin dose, study length, and participant characteristics. Therefore, the capsaicin consumption of most Koreans was below the levels that may cause adverse effects. However, more long-term studies for the dose range of 2–20 mg are required to further characterize capsaicin’s health benefits in Koreans.
... Oral ingestion and infusion of a chili powder solution is known to elicit heartburn symptoms in normal healthy subjects. 11,12 Therefore, the goals of our study were to determine: (1) if esophageal mucosal/submucosal injection of acid and capsaicin elicits symptoms in normal healthy subjects. ...
... They also found a correlation between the density of TRPV1 innervation and total acid exposure on 24-hour ambulatory pH monitoring (P = 0.03). 12 Bhat et al 16 described TRPV1 staining structures that appeared as free nerve endings in the epithelial layer, close to the surface of the mucosa, which we did not observe. Clearly, our immunostaining technique is specific for TRPV1 receptors because no staining was seen in the presence of the TRPV1 antibody blocking peptide. ...
Article
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Background/aims: Transient receptor potential Vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus. Methods: Unsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2-7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill's Questionnaire, and symptom intensity using Visual Analogue Scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody. Results: Acid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91±3 and symptoms lasted for 25±1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. 85% of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field. Conclusions: The mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain.
... (3,4) While another study in heartburn sufferers found that oesophageal and gastric pH profiles and gastric emptying were not different between meals with or without 5 mg of capsaicin in capsules. (5) Therefore, the aim of this study was to evaluate the effect of acute ingestion of red chili powder with meal on gastro-oesophageal reflux symptoms, esophageal pH profiles, and gastric emptying in patients with typical GORD symptoms. ...
... Capsaicin did not alter mean heartburn and dyspepsia scores but significantly decreased time to peak heartburn. (5) Recent study suggest that the chronic ingestion of chili significantly increase acid reflux variables in healthy volunteers. (6) Our study was designed to evaluate the effect of acute ingestion of red chili powder which represented the most physiologically by consumed meal with or without chili on gastro-oesophageal reflux, esophageal pH, and gastric emptying in patients with reflux like dyspepsia. ...
Article
Spicy foods, or red chili ingestion has been considered as an aggravating factor of gastro-oesophageal reflux symptom. But the effect of chili on gastro-oesophageal reflux disease (GORD) has not been well under-stood. Aims: To determine the effect of acute ingestion of red chili powder with meal on gastro-oesophageal reflux, and gastric emptying in patients with gastro-oesophageal reflux symptoms. Methods: Twelve patients with typical GORD symptoms, each underwent simultaneous esophageal pH and gastric emptying scintigraphy study after ingestion of 2 different test meals (i) standard meal (instant noodle with egg) (ii) standard meal with chili (instant noodle with egg mixed with 2 gm of red chili powder) in randomized, cross-over fashions, with a 1-week washout period. Gastrointestinal symptoms were evaluated by 100 mm visual analog scale (VAS). Results: After the test meal ingestion, 11 subjects completed the study. After ingestion, both standard meal and spicy meal increased gastro-oesophageal reflux. An increase in gastric retention was observed at 1 st hour after spicy meal ingestion compared with standard meal (p = 0.05). Number of gastro-oesophageal reflux, % time pH <4 in distal esophagus, mean esophageal and gastric pH, and gastro-oesophageal reflux symptoms were not different between standard meal and standard meal with red chili (p >0.05). However, in patients with positive 24-hour esophageal pH test, there was a significant increase in acid reflux number at 2 nd hour. This difference was not observed in patients with negative 24-hour esophageal pH test. Conclusion: After meal ingestion, both standard meal and spicy meal induced an increase in gastro-oesophageal acid refluxes. During the 2 nd hour after ingestion, spicy meal induced more acid reflux. This sug-gested that spicy meal ingestion induce acid reflux longer than standard meal and this may be associated with an increase in food retention in the stomach.
... These products cause or aggravate GERD symptoms by various mechanisms, e.g. decreasing tension of the LES, delaying stomach evacuation, stimulating sensory receptors in the oesophagus, or increasing gastric juice secretion [13][14][15][16]. In the present study, patients reported symptoms most often after consumption of the following products/dishes: fatty, fried, sour, or spicy food, fruits and sweets (mostly chocolate). ...
... These results were also confirmed by our study. Sour products, fruits and fruit juices -due to low pH -and spicy products/dishes -due to the presence of irritant alkaloids, such as capsaicin -stimulate mechanoreceptors in the oesophagus, which may cause unpleasant symptoms, especially if inflammatory lesions of the mucous membrane are present in the oesophagus [14,16,26]. Dore et al., in turn, did not confirm the association between chocolate products and the disease symptoms [9]. ...
Article
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Introduction: Nutrition can contribute to the development of gastroesophageal reflux disease (GERD). The relevant studies often provide contradictory results. Aim: To determine GERD risk factors associated with dietary habits. Material and methods: A total of 513 subjects were included. The study group consisted of adults with a recent clinically confirmed diagnosis of GERD, and the control group were healthy adults. The research tool was a proprietary questionnaire. Risk factors were evaluated by logistic regression models. Results: An association was found between the severity of typical GERD symptoms and a certain diet (p < 0.001). The symptoms were experienced more often after fatty, fried, sour, or spicy food and sweets. The univariate logistic regression analysis showed the following risk factors: eating 1-2 meals per day (OR = 3.50, 95% CI: 1.75-6.98), everyday consumption of peppermint tea (OR = 2.00, 95% CI: 1.14-3.50), and eating one, big meal in the evening instead of dinner and supper (OR = 1.80, 95% CI: 1.05-3.11). The multivariate analysis confirmed that frequent peppermint tea consumption was a risk factor (OR = 2.00, 95% CI: 1.08-3.70). Conclusions: Taking into consideration the results of this study, it seems that patients should be recommended to eat more than three meals a day and eat dinner and supper at appropriate times instead of one, big meal in the evening. The role of frequent peppermint tea consumption in GERD development requires further studies.
... The activation of TRPV1 receptor increases the release of calcium by sarcoplasmic reticulum, thus resulting in enhanced interaction between actin-myosin filaments, delaying muscle fatigue, and improving force production capacity [14]. Another mechanism that partially explains the ergogenic effects of capsaicin supplementation is the activation of TRPVI in the central nervous system, enhancing epinephrine and norepinephrine secretions during exercise [27]. However, more research is necessary to investigate this mechanism in humans. ...
Article
This study aimed to investigate the effects of acute capsaicin analog (Capsiate - CAP) supplementation on maximal voluntary isometric contraction (MVIC) performance in healthy young men. Thirteen subjects (25.2±3.2 yrs) participated in the present study. In two different days separated by one week, the subjects ingested capsiate (12 mg) or placebo (starch: 12 mg) 45 minutes before a MVIC test. The MVIC test consisted of five 10-second knee extension maximal isometric contractions with 45 seconds of recovery between efforts. The peak force, mean force, minimum force, fatigue index, and area under the curve of each contraction were calculated. Main condition effect was found, with higher values of peak force (+4.83%, F=6.867, p=0.02), fatigue index (+8.96%, F=5.228, p=0.041), and area under the curve (+4.19%, F=4.774, p=0.04) for CAP compared to placebo, however, no interaction effect was found for any variable (F=0.090 to 1.356, p≥0.276). In summary, healthy young men produced higher maximal isometric force and delayed fatigue in the CAP condition compared to placebo condition (condition effect) but without significant difference between each effort.
... The analgesic properties of this substance were known more than a century ago, and a rich harvest of studies demonstrated that the topical application of capsaicin is able to relieve postherpetic neuralgia of skin and oral cavity, trigeminal neuralgia and cluster headache [26][27][28], as well as painful diabetic neuropathy and vesical neuropathic pain [29,30]. In addition, recent experiments demonstrated that repeated exposures of the esophageal mucosa to capsaicin-containing red pepper sauce ingested by patients suffering from heartburn produce an analgesic effect after a first phase of symptom worsening, suggesting the induction of a ''sensitization'' followed by a ''desensitization'' of the esophageal mucosa by capsaicin [31]. Similarly, capsaicin administered to patients with functional dyspepsia was found to be able to improve significantly epigastric pain and bloating after an initial period of worsening [32]. ...
Article
Abdominal pain, that characterizes irritable bowel syndrome (IBS) together with bloating and disordered defecation, is mainly related to a visceral hypersensitivity due to an increase of TRPV(1) nociceptive nerve fiber activity. As capsaicin contained in red pepper is able to desensitize the TRPV(1) fibres, we evaluated whether the red pepper oral administration can decrease the symptoms of visceral hypersensitivity in IBS patients. The study was performed on 50 patients with IBS diagnosed following Rome II criteria. After a 2-week washout period, 23 patients were planned to receive 4 pills/day, for 6 weeks randomly and in a double blind manner, each containing 150 mg of red pepper powder with a coat that dissolves in the colon, and 27 patients placebo. The patients scored each day in a diary the abdominal pain and bloating intensities following the 5-point Likert scale. The weekly symptom mean scores and the final patient subjective evaluation on treatment effectiveness were statistically compared among groups and intra-groups with appropriate tests. Eight patients dropped from the study: 6 in the red pepper group for abdominal pain and 2 in the placebo group. In 8 patients, the pills were reduced to 2/day, because of the abdominal pain at the onset of treatment. The intra-group comparisons showed that in patients taking red pepper the abdominal pain and bloating mean score values of the last weeks of treatment were significantly improved with respect to pre-treatment values, unlike patients taking placebo. The final patient subjective evaluation on the treatment effectiveness showed that red pepper group scored significantly better than placebo. The results of this preliminary study indicate that the chronic administration of red pepper powder in IBS patients with enteric-coated pills was significantly more effective than placebo in decreasing the intensity of abdominal pain and bloating and was considered by the patients more effective than placebo.
... Acute administration of capsaicin induces esophageal and gastric symptoms of heartburn in healthy individuals and gastroesophageal reflux disease (GERD) patients [16]. Acute capsaicin ingestion also hastens the time to peak heartburn symptoms and leads to greater acid reflux [17,18]. Chronic ingestion of chili peppers containing capsaicin induces GERD symptoms in otherwise healthy individuals suggesting the esophageal and gastric symptoms associated with acute capsaicin ingestion do not subside with chronic administration [19]. ...
Article
Capsaicin and evodiamine are 2 thermogenic agents recognized for their ability to stimulate the sympathetic nervous system. We hypothesized that both capsaicin and evodiamine would be effective at increasing thermogenesis and lipid oxidation during rest and exercise. In a randomized, cross-over design, 11 men ingested 500 mg of cayenne pepper (1.25 mg capsaicin), 500 mg evodiamine, or placebo at rest following 30 minutes of energy expenditure assessment using open-circuit spirometry. Energy expenditure was assessed again prior to commencing approximately 30 minutes of treadmill exercise at 65% peak oxygen consumption. Energy expenditure was assessed for another 30 minutes of the post-exercise period. Heart rate, blood pressure, core temperature, and venous blood samples were obtained 30 minutes before supplement ingestion, 1 hour after supplement ingestion, immediately post-exercise, and 45 minutes post-exercise. Serum markers of lipid oxidation (glycerol, free fatty acids, glucose, epinephrine, and norepinephrine) were determined spectrophotometrically with enzyme-linked immunosorbent assay. Two-way analyses of variance with repeated measures were performed for each dependent variable (P ≤ .05) with Supplement and Test as main effects. Statistical analyses revealed significant main effects for Test for hemodynamics, energy expenditure, serum catecholamines, and markers of fat oxidation immediately post-exercise (P < .05). No significant interactions between Supplement and Test were noted for any criterion variable (P > .05). These results suggest that acute ingestion of 500 mg of cayenne (1.25 mg capsaicin) or evodiamine is not effective at inducing thermogenesis and increasing fat oxidation at rest or during exercise in men.
... In heartburn patients, 5 mg of capsaicin mixed to the meal significantly decreased the peak to the heartburn. When refluxed, capsaicin probably sensitized the oesophagus and primed it to noxious stimuli such as acid (Rodriguez-Stanley et al. 2000). Intraesophageal capsaicin infusion has been found to lower sensory and pain thresholds to oesophageal balloon distension, again presumably through direct activation of TRPV-1 and release of neurotransmitters (Gonzalez et al. 1998). ...
Article
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Calcitonin gene-related peptide (CGRP), a 37 aminoacid-residue peptide, is a marker of afferent fibers in the upper gastrointestinal tract, being almost completely depleted following treatment with the selective neurotoxin capsaicin that targets these fibers via transient receptor potential vanilloid type-1 (TRPV-1). It is widely distributed in the peripheral nervous system of mammals where it is present as alpha isoform, while intrinsic neurons of the enteric nervous systems express predominantly CGRP-beta. Many gastrointestinal functions involve CGRP-containing afferent fibers of the enteric nervous system such as defense against irritants, intestinal nociception, modulation of gastrointestinal motility and secretion, and healing of gastric ulcers. The main effects on stomach homeostasis rely on local vasodilator actions during increased acid-back diffusion. In humans, release of CGRP through the activation of TRPV-1 has been shown to protect from gastric damage induced by several stimuli and to be involved in gastritis. In both dyspepsia and irritable bowel syndrome the repeated stimulation of TRPV-1 induced an improvement in epigastric pain of these patients. The TRPV-1/CGRP pathway might be a novel target for therapeutics in gastric mucosal injury and visceral sensitivity.
... 7 Our new finding in current study is that repeated capsaicin exposure of the esophagus appears to lessen the intensity of heartburn symptom in healthy volunteers, which is in line with previous work in GERD patients that demonstrated an analgesic effect in perceiving heartburn after repeated exposure of the capsaicin. 26 The notion of desensitization of chemoreceptors after repetitive capsaicin infusion may support the evidence of the generation of heartburn symptom via TRPV1 receptor as established in our previous work. 27 Sensitization of TRPV1 by capsaicin has been widely accepted as important characteristics for this receptor. ...
Article
Background The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults.Methods Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed.Key ResultsAfter repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p < 0.001) and rapid air injections (p = 0.004). Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn perception (p < 0.001), but the intensity of heartburn perception was significantly reduced after repeated capsaicin-contained red pepper sauce infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections (p = 0.003).Conclusions & InferencesRepeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus.
... Acute administration of capsaicin induces esophageal and gastric symptoms of heartburn in healthy individuals and gastroesophageal reflux disease (GERD) patients [16]. Acute capsaicin ingestion also hastens the time to peak heartburn symptoms and leads to greater acid reflux [17,18]. Chronic ingestion of chili peppers containing capsaicin induces GERD symptoms in otherwise healthy individuals suggesting the esophageal and gastric symptoms associated with acute capsaicin ingestion do not subside with chronic administration [19]. ...
Article
Obesity has become a global epidemic within the last 25 years, with about 65% of the adult population in America being classified as either overweight or obese. In response to this epidemic, countless dietary supplements have emerged in recent years as an easy option to assist in the weight loss process. Capsaicin and evodiamine are two thermogenic agents each recognized for their ability to stimulate the sympathetic nervous system and are thus found in many dietary supplements. The exact effects of each agent, however, remain uncertain. In this randomized, cross-over experiment, seven healthy men were given either capsaicin, evodiamine, or a placebo supplement to ingest. Hemodynamics (heart rate, blood pressure, and core body temperature), energy expenditure, and markers of lipid oxidation (serum glycerol and free fatty acids) were measured at rest, after supplementation, after a single bout of moderately-intense exercise, and during recovery. Analyses of variance (ANOVA) were performed for each variable in order to determine whether between-group measurement differences were statistically significant, thus establishing measurable benefits, if any, that these agents offer to the body's metabolic system.
... Evidence also suggests that a number of agents (e.g., ethanol, prostaglandins, and others) may sensitize the TRPVR1 receptor and induce esophageal symptoms (28) . Capsaicin ingested in the meal also lowers the time to postprandial heartburn in patients with GERD (29) . ...
... As we have seen throughout this chapter, capsaicin has complex physiological effects, eliciting both pain and producing analgesia, both mucosal protection and injury. In light of the complex and seemingly conflicting actions, capsaicin has been referred to as a `double-edged sword' (Rodriguez-Stanley et al., 2000). Studies performed in human beings have demonstrated that capsaicin seems to protect oesophageal and gastric mucosa trough increasing regional blood flow (Bass et al., 1991; Kang et al., 1996; Teng et al., 1998). ...
Chapter
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Capsaicinoids are important for the food and pharmaceutical industries. For this reason, a number of researchers are engaged in improving their production by manipulating chili plant cultivation conditions, chemical and enzymatic synthesis processes or alternative methods such as cell or tissue culture. Hitherto, research has shown that capsaicinoids, and capsaicin in particular, have a wide variety of biological and physiological activities, providing them with different functions such as antioxidant, anticarcinogenic, anti-inflammatory, promoter of energy metabolism and suppressor of fat accumulation. However, the potential applications of these molecules are limited by the irritation caused by their pungency. This has driven the search and characterization of analogous molecules without these inherent and undesirable effects (Reyes-Escogido et al., 2011). Among them, capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a primary pungent and irritating substance present in chilies and red peppers, which are widely used as spices. Capsaicin evokes numerous biological effects and therefore has been the target of extensive investigations since its initial identification in 1919 by E. K. Nelson. Different pharmacological effects have been attributed to capsaicin since ancient times, but it was not until the past twenty years when extensive research has been done to determine its specific applications. In this chapter we will review the last results obtained in research, considering their application to Veterinary Medicine, not only for its therapeutic role (pain, arthritis, muscle injury, obesity, anthelminthic) but also as a preventive tool for digestive diseases, such as ruminal acidosis or gastric pain. In addition, supplementation of this compound in combination with other plant extracts has been proven to contribute improving animal production in ruminant livestock.
... In the upper abdomen, capsaicin intake enhanced the postprandial heartburn in humans (Rodriguez-Stanley et al., 2000) and this may be related to the high expression of sensory neurons (Koide et al., 2020). What's more, capsaicin removed the hydrophobicity of stomach, which led to the increase of pain sensitivity in rats (Lichtenberger et al., 1998) a '↑' indicates significantly increased and '↓ indicates significantly decreased. ...
Article
Background Chili peppers are commonly consumed spices worldwide and capsaicin is the main source for the spicy flavors, which is reported to have many biological activities. However, long-time consumption of chili peppers may probably cause the gastrointestinal discomfort due to the strong pungency of capsaicin. The beneficial and adverse effects of capsaicin on gastrointestinal health and the underlying mechanisms haven't been revealed. Scope and approach The review summarized the effects of capsaicin ingestion on the gastrointestinal tract and their possible mechanisms, illustrated the current and potential strategies for relieving capsaicin-induced discomfort, and provided insight into further studies on capsaicin and gastrointestinal health. Key Findings and Conclusions: Long-term and high levels of capsaicin ingestion may cause gastrointestinal discomfort and affect gastrointestinal digestion, which is more pronounced in specific gastrointestinal disorders. By analyzing the possible mechanisms, we found that capsaicin receptor TRPV1 and the neuropeptides can regulate the visceral pain and immune response, thereby affecting the oxidative stress and tissue permeability of the gastrointestinal tract. Furthermore, capsaicin can alter the structure of gut microbiota and affect the levels of short chain fatty acids (SCFAs). Current strategies can only decrease the oral pungent taste, but cannot relieve the gastrointestinal discomfort. Based on the effects of probiotics on gastrointestinal disorders and the correlation studies between probiotics and TRPV1, probiotics have the potential to relieve the capsaicin-induced gastrointestinal discomfort.
... In heartburn patients, 5 mg of capsaicin mixed to the meal significantly decreased the peak to the heartburn. When refluxed, capsaicin probably sensitized the esophagus and primed it to noxious stimuli such as acid [10]. Intraesophageal capsaicin infusion has been found to lower sensory and pain thresholds to esophageal balloon distension, again presumably through direct activation of TRPV-1 and release of neurotransmitters [11]. ...
Article
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Capsaicin, a pharmacologically active agent found in chili peppers, causes burning and itching sensation due to binding at the transient receptor potential vanilloid-1 (TRPV-1) receptor, a polymodal receptor critical to the sensing of a variety of stimuli (e.g., noxious heat, bidirectional pH), and subsequent activation of polymodal C and A-δ nociceptive fibers. Acutely, TRPV-1 activation with peripheral capsaicin produces pronociceptive effects, which extends to the development of hyperalgesia and allodynia. However, capsaicin has been reported to display antinociceptive properties as well, largely through TRPV-1-dependent mechanisms. Local application of high concentration of capsaicin is used for neuropathic pain and repeated stimulation of TRPV-1 induced an improvement of epigastric pain in irritable bowel syndrome and dyspepsia patients by desensitization of nociceptive pathways. New TRPV-1 agonists are currently under preclinical study and TRPV-1 antagonists are in early clinical development as analgesics. The TRPV-1 pathway might be a novel target for therapeutics in pain sensitivity.
... As we have seen throughout this chapter, capsaicin has complex physiological effects, eliciting both pain and producing analgesia, both mucosal protection and injury. In light of the complex and seemingly conflicting actions, capsaicin has been referred to as a `double-edged sword' ( Rodriguez-Stanley et al., 2000). Studies performed in human beings have demonstrated that capsaicin seems to protect oesophageal and gastric mucosa trough increasing regional blood flow ( Bass et al., 1991;Kang et al., 1996;Teng et al., 1998). ...
Chapter
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a naturally occurring alkaloid derived from plants of the genus Capsicum. TRPV1 (transient receptor potential vanilloid-1), a capsaicin receptor, is expressed in primary sensory neurons of dorsal root ganglia and vagal nerves. Heat and protons as well as capsaicin activate TRPV1 to induce the influx of cations, particularly Ca2+ and Na+ ions. Characteristic effects of capsaicin are the induction of a burning sensation after acute administration and the desensitization of sensory neurons after large doses and prolonged administration. Also, activation of capsaicinsensitive terminals enhances release of neuropeptides, for example substance P and calcitonin gene-related peptide. The use of capsaicin in animal models is important in the study of both processing and modulation of pain signals. Systemic treatment with the capsaicin is known to establish a long-lasting depletion of certain populations of afferent neurons and nerve fibers. Capsaicin induced different morphologic changes when given in different doses and at different ages. Administration of capsaicin modified age-related changes in the number of sensory neurons, containing TRPV1-receptors, calcitonin gene-related peptide, substance P, neurofilament 200.
... Indeed, simultaneous intraesophageal impedance and pH measurement in patients with persistent symptoms despite acid-suppressive therapy demonstrated that symptoms were associated with non-acid reflux in around a third of patients [19][20][21]. Other constituents of gastric contents may induce esophageal symptoms [22,23], with bile and pepsin both identified as contributing to reflux episodes [23,24]. ...
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Background: Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). Methods: Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20 mg) or Losec (20 mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). Results: Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0-30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. Conclusions: Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type. Trial registration: ClinicalTrials.gov NCT01493089.
... Many GERD patients report the presence or worsening of heartburn after eating spicy food, including chili pepper. It has been suggested that some of the symptoms associated with chili pepper consumption could be caused by the stimulation of nerve endings in the esophageal mucosa by capsaicin contained in hot peppers [7,37,69,74]. ...
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Gastroesophageal reflux disease (GERD) is one of the most common diseases of the upper gastrointestinal tract. The most characteristic symptom of the disease is heartburn, which occurs at least once a week. The prevalence of the disease varies and, depending on the region of the world, it may affect from a few to over 30% of an adult population. It is estimated that in Poland this disease may affect up to 35.5% of adults reporting abdominal ailments. If untreated, the disease can lead to serious complications including precancerous conditions and esophageal adenocarcinoma. Pharmacotherapy is considered as the first-line treatment in GERD patients but lifestyle modifications, including diet changes, are an important element supporting the treatment of the disease. Many factors may contribute to the development of the disease. Among them, there are non-modifiable factors such as age, sex or genetic factors and modifiable factors, e.g. lifestyle, diet, excessive body weight. This review focuses on GERD risk factors related to lifestyle and nutrition that include both dietary components and nutritional behaviour. Lifestyle risk factors that may contribute to GERD symptoms include excessive body weight, particularly obesity, moderate/high alcohol consumption, smoking, postprandial and vigorous physical activity, as well as lack of regular physical activity. Many studies indicate fatty, fried, sour, spicy food/products, orange and grapefruit juice, tomatoes and tomato preserves, chocolate, coffee/tea, carbonated beverages, alcohol as triggers for GERD symptoms. Eating habits such as irregular meal pattern, large volume of meals, eating meals just before bedtime may correlate with the symptoms of GERD. The role of lifestyle, diet and eating habits as risk factors for GERD is not clearly understood, and the results of the available studies are often contradictory. Determination of modifiable risk factors for this disease and its symptoms is important for effective dietary prevention and diet therapy of GERD.
... Evidence in the medical literature of such an effect, however, is quite limited. A small blinded, controlled trial demonstrated a reduction in time to cause symptoms of heartburn when capsaicin was provided along with a test meal [102]. Evidences suggest that Fatty foods seem to be the main trigger, but other foods such as: unfermented milk and dairy products, citrus fruits, spicy foods, coffee, alcohol, high intake of salt and soy sauce have also been concerned. ...
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Pathologies of the upper gastrointestinal (GI) tract, including peptic ulcer disease (PUD), dyspepsia, and gastro esophageal reflux disease (GERD), are very common. Dietary factors are increasingly recognized to have an important role in triggering symptoms in a large proportion of patients with PUD and dyspepsia. Fatty foods seem to be the main trigger, but other foods such as: carbonated beverages, unfermented-milk and dairy products, citrus fruits, spicy foods, coffee and alcohol have also been implicated. On the other hand diets rich in fiber, fermented-milk, polyunsaturated fatty acids (specially n-6 family), foods that contain flavonoids, such as apples, celery, cranberries, and cranberry juice may inhibit the growth of Helicobacter pylori and vitamin A and C seem to be positive role in alleviating the symptoms. However, blind challenge tests do not provide consistent results. Moreover, although patients identify specific foods as triggers of their peptic ulcer symptoms, these patients often do not seem to make behavioral adjustments in an attempt to improve those symptoms; that is, any differences in dietary intake and lifestyle between patients and healthy individuals are small. Patients with functional dyspepsia exhibit mixed sensory-motor abnormalities, such as gastric hypersensitivity and impaired gastric accommodation of a meal. Nutrients, particularly fat, exacerbate these abnormalities and might thereby trigger postprandial symptoms. Cognitive factors, including expectation related to previous negative experience with certain foods, might also have a role in triggering dyspeptic symptoms. This article review outlines a number of dietary options that could be used to alleviate the symptoms and as starting points for meaningful large-scale studies in the future. Keywords: Peptic Ulcer, Functional Dyspepsia, Helicobacter Pylori, Vitamin A and C, Flavonoids
... Intra-esophageal infusion with capsaicin-containing red pepper sauce suspension significantly decreased the thresholds of both perception and discomfort in response to esophageal balloon distension in healthy volunteers [43]. In healthy subjects who experienced heartburn after meals, capsaicin ingestion did not change the severity of standard meal-induced heartburn symptoms, but significantly decreased the time to reach the peak of heartburn score as measured at 15-min intervals within 7 h after a meal [44]. Intra-esophageal perfusion with an acid plus capsaicin solution significantly decreased the esophageal pain threshold to heat and Molecules 2021, 26, 3929 8 of 12 electric stimuli and increased the referred pain area to mechanical and electric stimuli in healthy subjects [45]. ...
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Heartburn and non-cardiac chest pain are the predominant symptoms in many esophageal disorders, such as gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), functional heartburn and chest pain, and eosinophilic esophagitis (EoE). At present, neuronal mechanisms underlying the process of interoceptive signals in the esophagus are still less clear. Noxious stimuli can activate a subpopulation of primary afferent neurons at their nerve terminals in the esophagus. The evoked action potentials are transmitted through both the spinal and vagal pathways to their central terminals, which synapse with the neurons in the central nervous system to induce esophageal nociception. Over the last few decades, progress has been made in our understanding on the peripheral and central neuronal mechanisms of esophageal nociception. In this review, we focus on the roles of capsaicin-sensitive vagal primary afferent nodose and jugular C-fiber neurons in processing nociceptive signals in the esophagus. We briefly compare their distinctive phenotypic features and functional responses to mechanical and chemical stimulations in the esophagus. Then, we summarize activation and/or sensitization effects of acid, inflammatory cells (eosinophils and mast cells), and mediators (ATP, 5-HT, bradykinin, adenosine, S1P) on these two nociceptive C-fiber subtypes. Lastly, we discuss the potential roles of capsaicin-sensitive esophageal afferent nerves in processing esophageal sensation and nociception. A better knowledge of the mechanism of nociceptive signal processes in primary afferent nerves in the esophagus will help to develop novel treatment approaches to relieve esophageal nociceptive symptoms, especially those that are refractory to proton pump inhibitors.
... In addition, we have recently observed that repeated esophageal exposure to red pepper sauce reduced the intensity of heartburn symptom in healthy volunteers [15] . The findings are in agreement with an earlier work in GERD patients that also noticed an analgesic effect in perceiving heartburn after repeated stimulation with the capsaicin [16] . ...
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AIM To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease (GERD). METHODS Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicin-containing red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 mL of red pepper sauce diluted with 15 mL of saline and 20 mL of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL/min with a randomized and double-blind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli. RESULTS Infusion of capsaicin significantly increased heartburn perception in patients with GERD (P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception (P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis (P = 0.001) and increased its frequency (P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion (P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis (P = 0.002) and reduced the frequency of secondary peristalsis (P = 0.02) during rapid air injection. CONCLUSION Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects.
... No subjects consumed alcohol as reported. Previous products may cause or aggravate GERD symptoms by various mechanisms, e.g., decreasing tension of the LES, delaying stomach evacuation, stimulating sensory receptors in the esophagus, or increasing gastric juice secretion [34,35]. There have been conflicting reports about the association of smoking and alcohol consumption to LPR. ...
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Background This was a prospective cohort that included 60 gastro-esophageal reflux disorder patients with suspected laryngopharyngeal reflux-related symptoms (e.g., sore throat, throat clearing, globus sensation, cough, dysphonia, and dysphagia). The diagnosis was confirmed using history taking, clinical laryngoscopic examination, and upper endoscopy guided by the Reflux Symptom Index (RSI). Patients were treated with proton pump inhibitors and prokinetics for 12 weeks. The aim of the current study was to explore the dietary risk factors in laryngopharyngeal reflux patients and to assess the response to therapy on swallowing-related problems by comparing the baseline pre-treatment and post-treatment values of RSI and Dysphagia Handicap index (DHI). Results Analysis of data regarding the role of diet as a risk factor for reflux revealed that 33 patients (55%) are eating meat, 56 patients (93.3%) eating fat, 45 patients (75%) eating sweet, 55 patients (91.7%) eating spicy food, 52 patients (96.7%) eating fried food, 34 patients (56.7%) drinking tea, 51 patients (85%) eating big meals, 21 patients (35%) drinking fruit juices, 54 patients (90%) eating sour foods, 51 patients (85%) eating citrus fruits, and 22 patients (36.7%) smokers. There was a statistically significant decrease in Reflux Symptom Index scores and an increase of Dysphagia Handicap Index scores after 12 weeks on proton pump inhibitors and prokinetics. Conclusion Different dietary factors were present in LPR patients. A short period of empiric anti-reflux treatment has a significant improving effect on Reflux Symptom Index and Dysphagia Handicap Index scores from baseline to 12 weeks post-treatment. Further research is needed to investigate longer times of treatment for the complete resolution of symptoms.
... Our findings that GERD symptoms were interlocked with cigarette smoking, drinking of alcohol, consumption of spicy, fatty, acidic, sweet, and hard foods are consistent with physiological studies [26][27][28] showing reduced esophageal pressure, accelerated gastric peristalsis, augmented secretion, delayed mucosal nerve-stimulated gastric emptying, augmented esophageal acid exposure, and aggrandized inflammation in relation to these food habits. Our discoveries of a connection between strong tea drinking and GERD stay in alignment with some other studies involving Chinese subjects, 29 though others have failed to find drinking of strong tea to be a significant risk factor for GERD. ...
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Background: Poor habits can worsen gastroesophageal reflux disease (GERD) and reduce treatment efficacy. Few large-scale studies have examined lifestyle influences, particularly eating habits, on GERD in China, and research related to eating quickly, hyperphagia, and eating hot foods is quite limited. The aim of this study was to evaluate the relationship between GERD pathogenesis and lifestyle factors to produce useful information for the development of a clinical reference guide through a national multicenter survey in China. Methods: Symptom and lifestyle/habit questionnaires included 19 items were designed. The questionnaire results were subjected to correlation analysis relative to GERD symptom onset. A standard proton pump inhibitor (PPI) was advised to correct patients with unhealthful lifestyle habits. Results: A total of 1518 subjects (832 GERD, 686 non-GERD) enrolled from six Chinese hospitals completed symptom and lifestyle/habit questionnaires. The top lifestyle factors related to GERD were fast eating, eating beyond fullness, and preference for spicy food. Univariate analysis showed that 21 factors, including male gender, a supra-normal body mass index (BMI), smoking, drinking alcohol, fast eating, eating beyond fullness, eating very hot foods, and drinking soup, among others, were associated with GERD (p < 0.05). Logistic multivariate regression analysis revealed the following risk factors for GERD [with odds ratios (ORs)]: fast eating (4.058), eating beyond fullness (2.849), wearing girdles or corsets (2.187), eating very hot foods (1.811), high BMI (1.805), lying down soon after eating (1.544), and smoking (1.521). Adjuvant lifestyle interventions improved outcomes over medication alone (z = -8.578, p < 0.001 Mann-Whitney rank sum test). Conclusions: Lifestyle interventions can improve medication efficacy in GERD patients. Numerous habits, including fast eating, eating beyond fullness, and eating very hot foods, were associated with GERD pathogenesis. The present results may be useful as a reference for preventive education and treatment.
... For example, red pepper (capsicum) contains the active component capsaicin, which has been studied specifically in patients with functional dyspepsia (49) . Oral intake of capsaicin in capsule form, and subsequent activation of chemoreceptors, induces dyspeptic symptoms in susceptible patients (49)(50)(51) . Similarly, the risk of reporting dyspepsia was associated with heavy (3 g day À1 ) dietary chilli intake in an urban multi-racial Asian population in Malaysia (52) . ...
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Background: Functional dyspepsia (FD) is a debilitating functional gastrointestinal disorder characterised by early satiety, post-prandial fullness or epigastric pain related to meals, which affects up to 20% of western populations. A high dietary fat intake has been linked to FD and duodenal eosinophilia has been noted in FD. We hypothesised that an allergen such as wheat is a risk factor for FD and that withdrawal will improve symptoms of FD. We aimed to investigate the relationship between food and functional dyspepsia. Methods: Sixteen out of 6451 studies identified in a database search of six databases met the inclusion criteria of studies examining the effect of nutrients, foods and food components in adults with FD or FD symptoms. Results: Wheat-containing foods were implicated in FD symptom induction in six studies, four of which were not specifically investigating gluten and two that were gluten-specific, with the implementation of a gluten-free diet demonstrating a reduction in symptoms. Dietary fat was associated with FD in all three studies that specifically measured this association. Specific foods reported as inducing symptoms were high in either natural food chemicals, high in fermentable carbohydrates or high in wheat/gluten. Caffeine was associated with FD in four studies, although any association with alcohol was uncertain. Conclusions: Wheat and dietary fats may play key roles in the generation of FD symptoms and reduction or withdrawal eased symptoms. Randomised trials investigating the roles of gluten, FODMAPs (fermentable oligosaccharide, disaccharide, monosaccharide and polyols) and high fat ingestion and naturally occurring food chemicals in the generation of functional dyspepsia symptoms are warranted and further investigation of the mechanisms is now required.
... Compared to the placebo, the red pepper capsules were associated with lower mean overall symptom intensity, epigastric pain, fullness and nausea scores than placebo [25 ]. This finding conflicts many of the observational and acute challenge studies where oral intake of capsaicin in capsule form induced dyspeptic symptoms [26,27]. It could be that acute challenges aggravate symptoms and that chronic ingestion reduces FD symptoms. ...
Article
The role of food in the development of symptoms experienced within functional gastrointestinal disorders (FGIDs) is well recognised. This review aims to describe the evidence base for dietary interventions in the different functional esophageal, duodenal and bowel disorders. Randomised controlled trials are lacking for many of the FGIDs, with the exception of irritable bowel syndrome (IBS). Restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) provides an evidence based dietary approach for the management of symptoms of IBS. Recent evidence shows the upper GI motility response varies between carbohydrates, which gives promise for the potential application of the low FODMAP diet in upper GI disorders. In addition to fine-tuning our FODMAP understanding, other observational data and smaller sized studies create an exciting and optimistic future for dietary management of all FGIDs.
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Although pharmaceutical as well as healthcare developments move forward, the initial management of dyspepsia, which usually starts off in primary care, still remains difficult to decide on. An average primary care physician deals with dyspepsia almost daily, and it accounts for major healthcare budgets in most countries. Unfortunately, evidence on which to base the best initial management strategy is still inconclusive. Most studies to date have reported on single drug comparisons or on comparison with prompt endoscopy and mainly involved patients either with persisting dyspeptic symptoms or with predominantly reflux-like symptoms, referred to secondary care. Several meta-analyses and reviews have been done to address important questions concerning treatment strategies for patients with dyspeptic symptoms. The Cochrane review on initial management of dyspepsia showed that only a few studies, mostly of inadequate methodology, dealt with this subject, and this Cochrane review was recently withdrawn [1]. Investigators concluded that large gaps in knowledge on the most cost-effective management strategy for uninvestigated dyspepsia still exist. Although new research was published, the final verdict on factors to be involved in the initial decision has still not been reached. Consequently, current guidelines for management of dyspepsia are inconsistent, and the cost-effectiveness of chosen strategies has substantial unknown variance depending on cultural and economical context. KeywordsDyspepsia-Cost-effectiveness-Diagnosis-Treatment strategies
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The term dyspepsia describes a heterogeneous group of symptoms originating from the epigastric region (stomach and duodenum). Dyspeptic symptoms include postprandial fullness, early satiation, epigastric pain, and epigastric burning (Table 5.1). Structural causes responsible for dyspeptic symptoms are discussed in Chap. 4. According to the Rome III consensus conference (2006), functional dyspepsia (FD) is defined as the presence of dyspeptic symptoms thought to generate in the gastroduodenal region, in the absence of organic, systemic, or metabolic disease that is likely to explain the symptoms [1]. Symptoms originating from the esophagus such as heartburn or regurgitation are not included in the current definition. For diagnosis of FD, the presence of one or more dyspeptic symptoms for the last 3 months with symptoms onset at least 6 months before diagnosis is required. Particularly for pathophysiological and therapeutic research purposes, the Rome III consensus conference defined two subentities of FD: KeywordsFunctional dyspepsia-Postprandial distress syndrome-Epigastric pain syndrome
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Functional dyspepsia (FD) is defined as the presence of dyspeptic symptoms thought to generate in the gastroduodenal region, in the absence of organic, systemic, or metabolic disease that is likely to explain the symptoms. The Rome III consensus conference defined two subentities of FD: the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). The variation of symptoms due to different pathophysiological mechanisms complicates the therapeutic response [1, 2]. The selection of the therapeutic approach should be dependent on the predominant symptom (Table 11.1) [3–5]. KeywordsFunctional dyspepsia-Therapy
Chapter
Chronic abdominal pain is the most common gastrointestinal symptom in children. According to the definition of Apley and Nash, recurrent abdominal pain occurs in more than three episodes over more than 3 months and is severe enough to affect daily activities of a child [1]. As in majority of children with chronic abdominal pain no clear structural or biochemical pathology can be found, the term “pain-related functional gastrointestinal disorders” has replaced the old term “chronic abdominal pain” [2, 3]. After the original definition, subgroups of the disorder have been described and according to the “Rome III” criteria a clinician can differentiate between functional dyspepsia (FD), irritable bowel syndrome, abdominal migraine, and functional abdominal pain (syndrome) (Table 15.1) [2]. Visceral sensation, hormonal changes, inflammation, motility disturbances, and psychological factors have all been suggested as contributory factors [3]. Despite the fact that disorders are by definition functional, symptoms may persist for years and the reported quality of life of children may be similar to children with inflammatory bowel disease or gastroesophageal reflux disease (GERD) [4]. KeywordsDyspepsia-Children-Epidemiology-Clinical presentation
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Dyspepsia, perceived as a very common and sometimes disabling problem, presents a formidable challenge to the clinician and clinical investigator alike. While we all can enumerate a number of symptoms that could be regarded as components of this “syndrome,” many, if not all, are nonspecific in terms of organ of origin or underlying pathophysiology. Overlap with other common symptomatic gastrointestinal disorders, such as functional heartburn and irritable bowel syndrome (IBS), is also an issue; where does dyspepsia end and reflux begin? It is in this context that definitions of dyspepsia, which can guide the clinician in diagnosis and therapy and provide the investigator with coherent study populations, must be developed.
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The definition of dyspepsia and its interpretation, as previously discussed in Chap. 1, are challenging. Encompassing a constellation of symptoms located in the retrosternal area, as well as in the upper abdomen, and potentially indicative of a number of ­different pathological processes, dyspepsia may have many and, in some cases, a number of causes. Although certain symptoms may seem, at first sight, more suggestive of the underlying pathology, efforts to identify which symptoms correlate with particular disease processes have been largely unsuccessful. In a seminal paper, Crean and colleagues attempted to define such clinico–pathological correlations and found that most supposed predictive symptoms did not hold up when critically examined. The most striking feature of this study, perhaps, was the uncertainty exhibited by clinicians when attempting to diagnose functional dyspepsia (FD), despite adequate investigation. This contrasted markedly with clinician certainty in diagnosing irritable bowel syndrome (IBS) [1]. KeywordsDyspepsia-Gastroesophageal reflux disease-Nonerosive reflux disease-Barrett’s esophagus-Peptic ulcer disease- Helicobacter pylori -Gastric carcinoma-Gallstones-Celiac disease-Gastric metastasis-Gastroparesis-Functional dyspepsia
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Dyspepsia – from the Latin word meaning “difficult (or abnormal) digestion” – is a symptom complex that encompasses, in variable combinations, such complaints as pain or discomfort localized in the upper abdomen, a subjective sense of bloating and/or an objective distension of the upper abdomen, nausea, early satiety and/or loss of appetite, regurgitation and/or vomiting, belching, and occasional heartburn. Children of preschool age usually cannot localize abdominal pain properly and cannot fully understand the concept of “nausea.” Small children usually report that they feel “sick” and/or “tummy/belly ache” and/or “butterflies in stomach” and/or other more or less imaginative definitions. Therefore, dyspepsia is more easily – and appropriately – diagnosed in school age children, where it appears to be a relatively common condition [1, 2]. Functional dyspepsia (FD) as defined by the Rome II criteria has a prevalence of 0.3% among children seen by primary care physicians in Italy and 12.5% to 15.9% among schoolchildren referred to tertiary care centers in the USA [3–5]. In any age group (including adulthood), the clinical manifestations of dyspepsia are entirely nonspecific and present a considerable overlap with manifestations related to conditions such as gastroesophageal reflux disease (GERD) (with or without esophagitis), irritable bowel syndrome (IBS), constipation, and gastrointestinal infections including gastritis due to Helicobacter pylori (H. pylori). KeywordsDyspepsia-Childhood-Gastric dysmotility-Food allergy-Endoscopy
Article
Dyspepsia is perhaps the most common gastrointestinal disease universally. The prevalence of dyspepsia ranges from 7-40% in population based studies worldwide. These figures vary with definition of dyspepsia used and also with the survey methodology. As with Western studies, functional dyspepsia (FD) predominates in Asia. With a decline in peptic ulcer disease and gastric cancer, the proportion of FD is set to increase further. Studies have shown FD to account for 50-70% of cases of uninvestigated dyspepsia. In Malaysia dyspepsia has been reported in up to 15% of a rural and 25% of an urban population. No racial differences were seen in the rural survey. In the urban survey, Malays and Indians were found to have significantly more dyspepsia than Chinese. No clear explanation can be found for these racial differences. In clinical practice, Malays seem to complain a lot of wind and bloating in the "stomach." This is interesting to note when you compare it with the prevalence of H. pylori which is distinctly less common amongst Malays compared to the Indians and Chinese. As with many Asian populations, many Malaysians do not consult for complains of dyspepsia. Many will self medicate and others may even bear with their complains. This is probably true in the rural population. Traditional medications are often used and these are often ethnic based. Different types of lotions for example are used for massaging the putative area in the abdomen by Malay, Chinese and Indian patients. Moxibustion and acupuncture is still practiced by Chinese traditional physicians for treatment of dyspepsia. The notion that mood disorders may underlies dyspepsia is still poorly accepted by a less educated or rural population who consider a psychiatric consultation a taboo. Amongst urban dwellers where Westernized medical care is readily available and the awareness of potential serious disease like cancer is higher, consultation for dyspepsia is certainly higher. Indeed a higher education level has been identified as independent risk factors for dyspepsia in both an urban and rural population survey in Malaysia. With greater consultation for dyspepsia, there has also been a higher demand and utilization of endoscopy services for investigation of gastrointestinal diseases in the country.
Article
Background: Type 1 vanilloid receptors (TRPV1) have been described on esophageal afferent sensitive neurons. Stimulation of TRPV1 receptors with capsaicin may induce heartburn. Capsaicin is the pungent component of chili and the most extensively studied TRPV1 agonist. Objectives: To investigate the effect of esophageal stimulation with intraesophageal capsaicin administration on induction of esophageal symptoms and on esophageal chemo-sensitization to acid in different gastroesophageal reflux disease (GERD) phenotypes. Methods: Healthy volunteers and patients with GERD (non-erosive [NERD], erosive GERD [EE] and Barrett's esophagus [BE]) were prospectively studied. All subjects were randomized to receive either intraesophageal perfusion capsaicin or saline 0.9%. Thirty minutes after saline or capsaicin infusion an acid perfusion test of HCl was performed. A week later, a crossover phase with capsaicin versus saline was performed. Five symptoms were evaluated every 5 min during the first 30 minutes after capsaicin, saline, and acid perfusion: chest burning, chest pain, heartburn, epigastric burning, and epigastric pain. Results: 17 healthy subjects and 31 GERD patients (10 NERD, 11 EE, and 10 BE) were included. Twenty- eight (90%) of GERD and 6 (35%) of healthy subjects had esophageal symptoms after capsaicin perfusion. Mean for the 5 evaluated symptoms induced by capsaicin was significantly higher in the GERD group compared to the control group. The highest symptom severity was in the erosive subgroup. Capsaicin decreased the 5 symptoms induced by acid perfusion in both healthy volunteers and GERD patients. Total score of esophageal symptom severity (produced by acid perfusion) was significantly reduced by capsaicin infusion in the BE group. Conclusions: Capsaicin induces esophageal and gastric symptoms in healthy volunteers and GERD patients. Capsaicin reduces esophageal chemosensitivity to acid, especially in patients with BE.
Article
Esophageal pain manifests as symptoms of heartburn, chest pain, or both. It shares features with other types of visceral pain in that it is poorly characterized and not well localized, owing to the divergence of visceral afferents. The esophagus is innervated by vagal and visceral spinal afferents, both of which are activated by noxious stimuli and convey information to specific centers within the central nervous system. Many stimuli can induce heartburn and chest pain; broadly, they can be divided into chemical stimuli (acid and others) and mechanical stimuli (distention and muscle spasm). The relationship between muscle spasm and chest pain has been an area of considerable controversy because of a poor temporal correlation between chest pain events and abnormal contractions in the esophagus. Recent studies suggest that spasm of the longitudinal muscles, rather than of circular muscle, may cause esophageal pain. Molecular mechanisms that link noxious stimuli with pain are not totally clear: the two leading contenders are vanilloid receptor 1 (VR1) and anion-sensing ion channels at the peripheral level. The role of esophageal hypersensitivity and psychiatric and psychological factors in the pathophysiology of esophageal pain remains an active area of investigation.
Chapter
Ein gastroösophagealer Reflux ist definiert als ein Rückfluss von Mageninhalt in den Ösophagus. Dies kann zu einer Ösophagitis infolge Irritation und Schädigung der Schleimhaut führen. Mitunter kann es von der erosiven Refluxkrankheit zum metaplastischen Umbau des Plattenepithels des Ösophagus zum Drüsenepithel im Sinne eines Barrett-Ösophagus bis hin zur Dysplasie und dem Adenokarzinom kommen.
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Patients with new-onset or recurrent dyspeptic symptoms, but without previous investigations (diagnostic procedures), primarily upper gastrointestinal (GI) endoscopy, are defined as having “uninvestigated dyspepsia.” Based on the results of performed ­diagnostic workup, patients are redefined as having organic ­(structural) or functional dyspepsia that subsequently requires appropriate specific management. Test-and-treat, empiric acid suppressive therapy, test-and-scope, and prompt endoscopy are diagnostic and therapeutic tools commonly applied in the management of uninvestigated dyspepsia. The choice of management strategy is determined by degree of possibility of underlying ­disease and cost effectiveness. Due to numerous randomized controlled trials (RCTs) that have compared these different strategies, the evidence base for the management of uninvestigated dyspepsia is one of the largest and most extensive ones, although RCTs have often been underpowered to observe plausible minor dissimilarities in symptom outcomes [1–8].
Article
Transient receptor potential (TRP) channels are members of an ancient class of ion channels that are present in most mammalian tissues. Consistent with their wide tissue distribution, TRPs are capable of influencing diverse physiological processes including adipocyte function, energy intake and energy expenditure. TRPs function as transduction channels downstream of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases, and some can also be direct sensors of chemical irritants that influence food intake or regulate body temperature and thermogenesis. TRP agonists were shown to reduce body weight and adiposity, suggesting that they might be exploited as therapeutic targets. In this review I discuss the current knowledge of how TRP channels influence energy balance.
Dramatic progress has been made over the past decade in the sophistication and availability of equipment to test esophageal motility and sensation. High-resolution esophageal manometry and impedance have moved from the research clinic into clinical practice. Some of the testing is costly and time consuming, and requires extensive experience to perform the testing and properly interpret the results. These sensory studies are valuable in the interpretation of clinical problems, and provide important research information. Clinicians should evaluate the research studies to advance their understanding of the pathophysiology of the esophagus.
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Gastroesophageal reflux is an extremely common condition often associated with chronic cough, dyspnea, laryngeal discomfort, and other extraesophageal symptoms. A considerable body of evidence has established an association of reflux with the presence of cough reflex hypersensitivity and/or bronchial hyperresponsiveness. However, the demonstration of such airway hyperreactivity does not uniformly predict the presence of underlying pathology nor the occurrence of symptoms. Furthermore, treatment aimed at suppressing cough reflex sensitivity or bronchial responsiveness, even when successful, often fails to ameliorate associated symptoms. Given that reflux, cough, and asthma are all very common conditions, the association of reflux with cough reflex hypersensitivity and bronchial hyperresponsiveness is likely causal in some individuals and coincidental in others. Adequately performed clinical trials evaluating the presence of pathological reflux, its effect on cough reflex sensitivity, airway responsiveness and pulmonary symptoms, as well as objective and symptomatic response to therapeutic interventions, will be most useful in elucidating the pathophysiologic manifestations of reflux on the respiratory system.
Article
Objectives: The diagnosis of functional dyspepsia (FD) is challenging due to the lack of reliable biological markers to support the diagnosis. We assessed the relevance of a previously validated simple test for chemical hypersensitivity in the setting of a gastrointestinal outpatient department. Methods: A total of 224 outpatients who were referred for evaluation of gastrointestinal symptoms in the absence of alarm symptoms swallowed a capsule containing 0.75 mg capsaicin. Severity of symptoms before and after capsule ingestion was assessed by a graded questionnaire and the difference in aggregate symptom scores (delta) was calculated. Results: Sensitivity of the test was between 0.51–0.59, specificity was 0.84–0.89 and positive predictive value for the diagnosis of FD 70–71%. FD patients had significantly higher median delta symptom scores (10.0; 25% quartile: 3.0; 75% quartile: 16.0) as compared to inflammatory bowel disease (2.5; 1.0/8.5)(P=0.003), peptic ulcer disease (0.0; −1.5/4.5) (P<0.001), irritable bowel syndrome (3.0;0.5/8.5)(P=0.001), and patients classified with “other disease” (2.5;0.0/5.0)(P<0.001). Patients with gastroesophageal reflux disease had significantly lower symptom scores if FD was not concomitantly diagnosed (2.0; 0.0/6.0) than if FD was present (10.0; 4.0/15.0). Conclusions: Hypersensitivity for capsaicin discriminates functional dyspepsia from patients with other GI disorders. The capsaicin test is a simple and non invasive method to detect a large subgroup of functional dyspepsia with chemical hypersensitivity. These findings might open new diagnostic options in functional dyspepsia and possibly new therapeutic options by targeting the specific capsaicin receptor TRPV1.
Article
Heartburn (pyrosis) can be defined as a burning sensation behind the sternum. Heartburn is typically caused by stomach acid that has refluxed back into the esophagus through the lower esophageal sphincter (which is normally closed except when swallowing). Most people who experience heartburn actually produce normal amounts of stomach acid, so heartburn is a problem of acid in the wrong place, not the production of too much acid. Lifestyle modifications that may reduce the risk of heartburn episodes include elevating the head of the bed by 6 to 8 inches, decreasing/avoiding certain foods (eg, chocolate, peppermint, fatty foods, caffeine, citrus, and tomatoes), avoiding large meals, and losing weight (decrease abdominal pressure). When lifestyle modifications are insufficient, there are numerous heartburn therapy options available over the counter. All 3 major categories of over-the-counter heartburn therapies are targeted at reducing acid already present in the esophagus (eg, antacids) or reducing gastric acid production (histamine 2 -receptor antagonists [H 2 RAs] and proton pump inhibitors [PPIs]). Antacids can provide rapid-onset heartburn relief by neutralizing acid already present in the esophagus. However, the transient increase in stomach pH caused by the antacid stimulates acid production, rapidly returning the stomach to a low pH. This rapid return to a low pH is why antacids do not prevent subsequent heartburn episodes and why frequent dosing (eg, up to 15 antacid tablets per day) may be required. Histamine 2 -receptor antagonists competitively inhibit 1 of the 3 stimuli for gastric acid production, which can slow acid production, so even a single dose can have a moderate effect on gastric pH. With repeat dosing, however, H 2 RAs rapidly develop tolerance that results in decreased acid control. While H 2 RAs can be effective for treating an isolated heartburn episode, they are less effective for controlling acid with repeat dosing (eg, frequent heartburn, defined as ≥2 days per week). Furthermore, H 2 RAs have an analgesic effect in the esophagus that is independent of acid control, so the esophagus may remain exposed to acid, even though the heartburn has been relieved. In contrast, PPIs block acid production at the final step, the proton pump, regardless of the 3 stimuli causing acid production. Proton pump inhibitors do not develop tolerance, and acid control actually increases over the first several days of dosing to a peak/sustained effect beginning on dosing day 4. Thus, PPIs provide both superior acid control and superior treatment of frequent heartburn when compared with H 2 RAs. Proton pump inhibitors show a dose-responsive effect on heartburn with less than 20 mg/d, but there is no additional heartburn control with higher doses (>20 mg), so the optimal dose for treatment of frequent heartburn is 20 mg/d. Treating frequent heartburn with a minimal effective dose is consistent with the 2013 treatment guidelines established by the American College of Gastroenterology. If frequent heartburn is not effectively treated with 2 weeks of an over-the-counter therapy, then the patient should be evaluated by a physician. Furthermore, the presence of 1 or more alarm symptoms (eg, difficulty swallowing, painful swallowing, gastrointestinal bleeding, iron deficiency/anemia, weight loss, early satiety, and vomiting) should be evaluated by a specialist.
Article
Gastroesophageal reflux disease is a chronic condition with a high prevalence in western countries. Transient lower esophageal sphincter relaxation episodes and a decreased lower esophageal sphincter pressure are the main mechanisms involved. Currently used drugs are efficient on reflux symptoms, but only as long as they are administered, because they do not modify the reflux barrier. Certain nutrients or foods are generally considered to increase the frequency of gastroesophageal reflux symptoms, therefore physicians recommend changes in diet and some patients avoid bothering foods. This review summarizes current knowledge regarding food and gastroesophageal reflux. For example, fat intake increases the perception of reflux symptoms. Regular coffee and chocolate induce gastroesophageal reflux and increase the lower esophageal exposure to acid. Spicy foods might induce heartburn, but the exact mechanism is not known. Beer and wine induce gastroesophageal reflux, mainly in the first hour after intake. For other foods, like fried food or carbonated beverages data on gastroesophageal reflux is scarce. Similarly, there is few data about the type of diet and gastroesophageal reflux. Mediterranean diet and a very low carbohydrate diet protect against reflux. Regarding diet-related practices, consistent data showed that a "short-meal-to-sleep interval" favors reflux episodes, therefore some authors recommend that dinner should be at least four hours before bedtime. All these recommendations should consider patient's weight, because several meta-analysis showed a positive association between increased body mass index and gastroesophageal reflux disease.
Chapter
Calcitonin gene-related peptide (CGRP), a 37 aminoacid-residue peptide, is a marker of afferent fibers in the upper gastrointestinal tract, being almost completely depleted following treatment with the selective neurotoxin capsaicin that targets these fibers via transient receptor potential vanilloid type-1 (TRPV-1). It is widely distributed in the peripheral nervous system of mammals where it is present as  isophorm while intrinsic neurons of the enteric nervous systems express predominantly CGRP-. Many gastrointestinal functions involve CGRP-containing afferent fibers of the enteric nervous system such as defense against irritants, intestinal nociception, modulation of gastrointestinal motility and secretion and healing of gastric ulcers. The main effects on stomach homeostasis rely on local vasodilator actions during increased acid-back diffusion. In humans, release of CGRP through the activation of TRPV-1 has been shown to protect from gastric damage induced by several stimuli and to be involved in gastritis. In both dyspepsia and irritable bowel syndrome the repeated stimulation of TRPV-1 induced an improvement of epigastric pain of these patients. The TRPV-1/CGRP pathway might be a novel target for therapeutics in gastric mucosal injury and visceral sensitivity.
Article
Dietary spices and their active constituents provide various beneficial effects on the gastrointestinal system by variety of mechanisms such as influence of gastric emptying, stimulation of gastrointestinal defense and absorption, stimulation of salivary, intestinal, hepatic, and pancreatic secretions. Capsicum annuum (Solanaceae), commonly known as chilli, is a medicinal spice used in various Indian traditional systems of medicine and it has been acknowledged to treat various health ailments. Therapeutic potential of chilli and capsaicin were well documented; however, they act as double-edged sword in many physiological circumstances. In traditional medicine chilli has been used against various gastrointestinal complains such as dyspepsia, loss of appetite, gastroesophageal reflux disease, gastric ulcer, and so on. In chilli, more than 200 constituents have been identified and some of its active constituents play numerous beneficial roles in various gastrointestinal disorders such as stimulation of digestion and gastromucosal defense, reduction of gastroesophageal reflux disease (GERD) symptoms, inhibition of gastrointestinal pathogens, ulceration and cancers, regulation of gastrointestinal secretions and absorptions. However, further studies are warranted to determine the dose ceiling limit of chilli and its active constituents for their utilization as gastroprotective agents. This review summarizes the phytochemistry and various gastrointestinal benefits of chilli and its various active constituents.
Article
Background: Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. Methods: Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. Key results: Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). Conclusions & inferences: Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.
Article
Dyspeptic symptoms are highly prevalent in the population and represent a major burden for healthcare systems. The ROME III criteria address and define two separate entities of functional dyspepsia: epigastric pain syndrome and postprandial distress syndrome. The etiology of dyspeptic symptoms is heterogeneous, underlying mechanisms are poorly understood and symptomatic improvement after drug therapy is often incomplete. This review of the literature included Medline data being published in the field of functional dyspepsia and different therapies. The reader will gain a current, unbiased understanding of the pathophysiological mechanisms underlying functional dyspepsia and of the therapeutic regimens based on randomized, controlled trials and on the meta-analyses that have been published on different therapeutic agents. Before starting medical treatment, a careful physical examination should exclude 'alarm symptoms'. Laboratory data, ultrasound and endoscopy are recommended in patients older than 45 - 55 years (depending on the guidelines being used). In areas with a high prevalence of Helicobacter pylori, the initial strategy includes 'test and treat' for H. pylori in addition to empiric acid suppressive therapy. Many studies have focused on the role of gastrointestinal dysmotility and hypersensitivity for dyspepsia with inconclusive results. Further therapeutic medical strategies include prokinetics, herbal preparations and psycho-/neurotopic drugs as well as additional psycho- or hypnotherapy.
Article
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We have developed a breath test to measure solid gastric emptying using a standardized scrambled egg test meal (250 kcal) labeled with [14C]octanoic acid or [13C]octanoic acid. In vitro incubation studies showed that octanoic acid is a reliable marker of the solid phase. The breath test was validated in 36 subjects by simultaneous radioscintigraphic and breath test measurements. Nine healthy volunteers were studied after intravenous administration of 200 mg erythromycin and peroral administration of 30 mg propantheline, respectively. Erythromycin significantly enhanced gastric emptying, while propantheline significantly reduced gastric emptying rates. We conclude that the [*C]octanoic breath test is a promising and reliable test for measuring the gastric emptying rate of solids.
Article
Full-text available
The *C (13C or 14C) labelled octanoic acid breath test was recently developed to measure the gastric emptying rate of solids. This study aimed to investigate whether it is sensitive enough to detect pharmacologically induced changes in the gastric emptying rate. Nine healthy volunteers were studied in basal condition, after intravenous administration of 200 mg erythromycin, and after peroral administration of 30 mg propantheline. Erythromycin significantly enhanced gastric emptying in all subjects, with an increase of the gastric emptying coefficient (p = 0.0043) in eight of nine and a fall in both the gastric half emptying time (p = 0.0020) and the lag phase (p = 0.0044) in all nine. Propantheline significantly reduced the gastric emptying rate, with a decreased gastric emptying coefficient (p = 0.0007) and an increased gastric half emptying time (p = 0.0168) in all subjects, but no change in the lag phase (p = 0.1214). Further mathematical analysis showed that breath sampling at 15 minutes intervals over a four hour period is recommended to guarantee accuracy and the discriminative value of the breath test in various gastric emptying patterns. In conclusion the *C labelled octanoic acid breath test is sufficiently sensitive to show pharmacologically induced changes of gastric emptying rates of solids.
Article
Objective: The accuracy of the 13C-octanoic acid breath test is enhanced by breath sampling over 6 h rather than 4 h, but this increases the cost of the test. Our aim was to validate a less costly but accurate sequence of breath sampling for measuring gastric emptying of solids. Methods: We performed the 13C-octanoic acid breath test and tested its reproducibility relative to simultaneous scintigraphy in 30 healthy volunteers. Results: There was a significant but weak correlation between t measured by the two tests (rs = 0.54, p < 0.005), but not between the duration of the lag phase. The differences in the t measurements between the tests were different between subjects but were highly reproducible within subjects. Within- and between-subject variations of measurements of gastric emptying with the 13C-octanoic acid breath test were not significantly different from the variations observed with scintigraphy. A subset of 11 breath samples collected over 6 h (24 samples) predicted (r2 > 0.95) the variables characterizing the cumulative appearance of 13CO2 in breath; these samples were at 35, 50, 95, 110, 140, 155, 215, 245, 260, 290, and 335 min. The accuracy of this subset of sampling times was confirmed in a separate set of breath test samples over 6 h from the same 30 subjects. Conclusions: The 13C-octanoic acid breath test for gastric emptying of solids is as reproducible as scintigraphy. A subset of 11 sampling times provides sufficient information to characterize the whole breath-test curve, but the sampling period should be extended to 6 h after dosing.
Article
The esophageal mucosa is exposed to damaging agents both by ingestion and reflux. Using our in vivo rabbit model of esophagitis, we have observed that acute luminal exposure (within 1 to 5 minutes) to potentially harmful agents, such as acid, bile, or ethanol, induces a rapid increase in mucosal blood flow; whereas prolonged exposure (10 to 60 minutes) results in mucosal injury and ablation of blood flow. We have also shown that capsaicin-sensitive mucosal afferent nerves can modulate esophageal blood flow. These findings led us to hypothesize that the reactive increase in blood flow induced by luminal agents represents a mechanism of protection mediated by capsaicin-sensitive nerves. The objective of these experiments was to determine if luminal capsaicin, a specific probe for visceral afferent nerves, could both preserve mucosal blood flow and protect against ethanol injury. Rabbits were subjected to luminal instillation of 50% ethanol with or without 1% capsaicin. Blood flow was measured with microspheres at baseline and after 2 and 10 minutes. Rabbits exposed only to ethanol developed severe mucosal injury coincident with near ablation of mucosal blood flow. In contrast, rabbits exposed to ethanol with capsaicin showed protection of the epithelium with a sixfold increase in mucosal blood flow. We conclude that capsaicin-sensitive nerves in the esophagus are local effectors of mucosal protection by virtue of preserving blood flow.
Article
Fatty foods have been identified as precipitating factors in symptomatic gastroesophageal reflux (GER). A fat meal has also been found to decrease lower esophageal sphincter pressure (LESP) in normal subjects. We used the ambulatory 24-h pH monitor to assess esophageal acid exposure in 10 normal subjects and 10 GER patients following low and high fat meals eaten in two body positions. The meals had nearly identical protein content, volumes, and calories. On successive days, patients ingested one of the meals twice, followed by random assignment to 3 h upright and 3 h recumbent position. Acid exposure for each hour over a 3-h postprandial (PP) period was assessed as the percent time pH less than 4.0. Increased upright acid exposure occurred in normals after the high fat (6.2 +/- 2.1%; mean +/- SE) compared with the low fat meal (1.5 +/- 0.5%; p less than 0.05). GER patients had greater (p less than 0.05) acid exposure than normals in all study periods, but no differences were found between low and high fat meals in either study position. High fat meals induce upright GER in normals, but do not significantly affect the abnormal amount of GER in patients. In addition, progressive increases in acid exposure were found over the 3 postprandial hours in GER patients in a recumbent position. The findings are consistent with prior data showing decreased LESP with a fat meal in normals.
Article
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a primary pungent and irritating principle present in chilies and red peppers which are widely used as spices. Because of its selective effects on the functions of a defined subpopulation of sensory neurons, capsaicin is currently used as a versatile tool for the study of pain mechanisms and also for pharmacotherapy to treat several pain disorders. Considering the frequent consumption of capsaicin as a food additive and its current medicinal use, correct assessment of hazardous effects of this compound is important. Mutagenic and carcinogenic activities of capsaicin and chili extracts have been studied, but results are conflicting. Mammalian metabolism of capsaicin has been also reported. Capsaicin appears to interact with xenobiotic metabolizing enzymes, particularly microsomal cytochrome P450-dependent monooxygenases which are involved in activation as well as detoxification of various chemical carcinogens and mutagens. Recent studies have shown that hepatic cytochrome P450 2E1 catalyzes the conversion of capsaicin to reactive species such as the phenoxy radical intermediate capable of covalently binding to the active site of the enzyme as well as tissue macromolecules. While covalent modification of protein and nucleic acids leads to toxicity including necrosis, mutagenesis, and carcinogenesis, suicidal inhibition of microsomal cytochrome P450 may prohibit further activation of capsaicin and also of other toxic xenobiotics. Results from recent studies indicate that capsaicin possesses the chemoprotective activity against some chemical carcinogens and mutagens.
Article
Anecdotes and animal experiments alike suggest that physiological and psychological stress can profoundly alter gastrointestinal function. However, few studies have examined, in humans, real-world stress to see if free-living persons exhibit gut alterations similar to those produced in the laboratory. To investigate this possibility, we studied 16 medical and premedical students during final written examinations. As compared to a control day, the examination created a classic stress response: elevated serum cortisol (16 +/- 1 to 21 +/- 3 micrograms/dl; P < 0.05), ACTH (31 +/- 1 to 33 +/- 1 pg/ml; P < 0.05), heart rate (72 +/- 3 to 79 +/- 3 beats/min; P < 0.05), arterial blood pressure (systolic pressure 106 +/- 2 to 120 +/- 2 torr; P < 0.05; diastolic pressure 72 +/- 2 to 77 +/- 1 torr; P < 0.05), and subjective anxiety (raw score 28 +/- 2 to 47 +/- 3; P < 0.0001). In contrast, subjects displayed identical orocecal liquid transit time (of 0.36 g/kg lactulose in a 240-ml, 250-kcal liquid meal) under control (103 +/- 8 min) and examination conditions (106 +/- 8 min; P = NS). Mean subjective reports of gas, diarrhea, and borborygmi were unchanged on the day of the experiment, although the examination did increase reported abdominal pain (from 0.5 +/- 0.4 to 2.1 +/- 0.5 on a 0-5 analog scale; P < 0.05). We conclude that examination stress in humans can increase gastrointestinal symptoms without altering orocecal transit.
Article
The aim of the present study was to develop a breath test for measuring gastric emptying rate of solids that would induce less radiation exposure than radioscintigraphy and would be applicable to field testing. A test meal was used in which [14C]-octanoic acid was mixed with egg yolk and prepared as a scrambled egg. The test meal was labeled with a second marker, 99mTc-albumin colloid, and simultaneous radioscintigraphic and breath test measurements were performed in 36 subjects, 16 normal controls, and 20 patients with dyspeptic symptoms. Mathematical analysis of the excretion rate of labeled CO2 resulted in the definition of three parameters, i.e., gastric emptying coefficient, gastric half-emptying time, and lag phase. There was an excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = -0.88); between the half-emptying time determined by the breath test and the scintigraphic half-emptying time (r = 0.89); and between the lag phases determined by scintigraphy and those determined by breath test (r = 0.92). 14C can be replaced by 13C for labeling the octanoic acid used in the breath test. It is concluded that the octanoic acid breath test is a reliable noninvasive test to measure gastric emptying rate of solids.
Article
Capsaicin protects the gastric mucosa against experimental injury while capsaicin desensitisation reduces the rate of gastric ulcer healing. The effect of exogenous capsaicin on gastric ulcer healing has not to date been reported. AIM/METHOD: To investigate the effect of capsaicin, cimetidine, and in combination, given intragastrically in the healing of acetic acid induced chronic gastric ulcer in the rat. Treatment started immediately after ulcer induction. At the end of one week, capsaicin, cimetidine, and in combination increased ulcer healing but the effect of combined treatment was less than that of capsaicin alone. In an in vivo gastric chamber preparation, capsaicin increased, while cimetidine decreased, gastric mucosal blood flow measured by laser Doppler flowmetry. A dose response effect in reduction of gastric mucosal blood flow could be demonstrated for cimetidine. The gastric hyperaemic effect of capsaicin was blunted by prior administration of cimetidine. In contrast, capsaicin had no effect on gastric acid secretion and its addition to cimetidine did not affect the acid suppressant effect of the latter. Capsaicin promotes the healing of acetic acid induced gastric ulcer, probably by its gastric hyperaemic effect. Although cimetidine also promotes ulcer healing due to its inhibitory effect on acid secretion it may have an antagonistic effect on the gastric ulcer healing effect of capsaicin by virtue of inhibition of gastric hyperaemia.
Article
Previous work suggested that a breath test using 13C accurately measures gastric emptying of solids. Thus, breath test half emptying time (t1/2) minus 66 minutes was claimed to estimate accurately t1/2 by scintigraphy. The aim of this study was to evaluate the accuracy and reproducibility of this breath test in healthy subjects. Fifteen volunteers (8 men and 7 women; mean age, 41 +/- 13 years) underwent simultaneous scintigraphy and [13C]octanoic acid breath test. Scans and breath samples were obtained every 15 minutes for 4 and 6 hours, respectively. The breath test was repeated three times within a 3-week period. Parameters from scintigraphy and breath test were not correlated significantly. Differences of lag phase and t1/2 between the two tests were highly variable (range for t1/2, -33.1 to 169.6; mean, 48.0 minutes). Increasing breath test "duration" (samples over 4, 5, or 6 hours) yielded decreasing estimates of the lag phase and t1/2. Although widely different values were observed in some subjects, repeated breath tests showed a high degree of reproducibility within individuals (mean coefficient of variation, 12%). [13C]Octanoic acid breath test for gastric emptying of solids requires further validation before it can substitute for scintigraphy as a diagnostic test, but it seems useful for intraindividual comparisons.
Article
Nonspecific esophageal motility disorder (NEMD) is a vague category used to include patients with poorly defined esophageal contraction abnormalities. The criteria include "ineffective" contraction waves, ie, peristaltic waves that are either of low amplitude or are not transmitted. The aim of this study was to identify the prevalence of ineffective esophageal motility (IEM) found during manometry testing and to evaluate esophageal acid exposure and esophageal acid clearance (EAC) in patients with IEM compared to those with other motility findings. We analyzed esophageal manometric tracings from 600 consecutive patients undergoing manometry in our laboratory following a specific protocol from April 1992 through October 1994 to identify the frequency of ineffective contractions and the percentages of other motility abnormalities present in patients meeting criteria for NEMD. Comparison of acid exposure and EAC was made with 150 patients who also had both esophageal manometry and pH-metry over the same time period. Sixty-one of 600 patients (10%) met the diagnostic criteria for NEMD. Sixty of 61 (98%) of these patients had IEM, defined by at least 30% ineffective contractions out of 10 wet swallows. Thirty-five of these patients also underwent ambulatory esophageal pH monitoring. Patients with IEM demonstrated significant increases in both recumbent median percentage of time of pH <4 (4.5%) and median distal EAC (4.2 min/episode) compared to those with normal motility (0.2%, 1 min/episode), diffuse esophageal spasm (0%, 0.6 min/episode), hypertensive LES (0%, 1.8 min/episode), and nutcracker esophagus (0.4% 1.6 min/episode). Recumbent acid exposure in IEM did not differ significantly from that in patients with systemic scleroderma (SSc) for either variable (5.4%, 4.2 min/episode). We propose that IEM is a more appropriate term and should replace NEMD, giving it a more specific manometric identity. IEM patients demonstrate a distinctive recumbent reflux pattern, similar to that seen in patients with SSc. This finding indicates that there is an association between IEM and recumbent GER. Whether IEM is the cause or the effect of increased esophageal acid exposure remains to be determined.
Article
Psychophysical methods were used to assess changes in the intensity of irritant sensations elicited by repeated application of capsaicin and nicotine delivered unilaterally to the tongue of human subjects. Whereas capsaicin (0.5 or 3 p.p.m.; repeated at 1 min intervals over 10 min) evoked progressively stronger ratings of irritation (sensitization), there was a significant decrement in irritation ratings (desensitization) to repeated application of nicotine (0.1%). A two-alternative forced-choice (2-AFC) procedure was additionally used to test for self- and cross-desensitization. After the subjects had received either repeated capsaicin or nicotine, a rest period ensued followed by the 2-AFC procedure. Either capsaicin or nicotine was delivered bilaterally to the tongue and subjects were asked to choose which side yielded a stronger sensation. Following capsaicin pretreatment, subjects reported that capsaicin evoked a stronger sensation on the previously untreated side (capsaicin self-desensitization). Similar self-desensitization was observed with nicotine. Furthermore, nicotine evoked a significantly weaker sensation on the side of the tongue pretreated with capsaicin (cross-desensitization). In contrast, capsaicin did not consistently evoke a weaker sensation on the nicotine-pretreated side, indicating an absence of cross-desensitization. These results are discussed in terms of physiological mechanisms that might underlie the contrasting sensory effects of nicotine versus capsaicin.
Article
The accuracy of the 13C-octanoic acid breath test is enhanced by breath sampling over 6 h rather than 4 h, but this increases the cost of the test. Our aim was to validate a less costly but accurate sequence of breath sampling for measuring gastric emptying of solids. We performed the 13C-octanoic acid breath test and tested its reproducibility relative to simultaneous scintigraphy in 30 healthy volunteers. There was a significant but weak correlation between t1/2 measured by the two tests (rs = 0.54, p < 0.005), but not between the duration of the lag phase. The differences in the t1/2 measurements between the tests were different between subjects but were highly reproducible within subjects. Within- and between-subject variations of measurements of gastric emptying with the 13C-octanoic acid breath test were not significantly different from the variations observed with scintigraphy. A subset of 11 breath samples collected over 6 h (24 samples) predicted (r2 > 0.95) the variables characterizing the cumulative appearance of 13CO2 in breath; these samples were at 35, 50, 95, 110, 140, 155, 215, 245, 260, 290, and 335 min. The accuracy of this subset of sampling times was confirmed in a separate set of breath test samples over 6 h from the same 30 subjects. The 13C-octanoic acid breath test for gastric emptying of solids is as reproducible as scintigraphy. A subset of 11 sampling times provides sufficient information to characterize the whole breath-test curve, but the sampling period should be extended to 6 h after dosing.
Article
C-fiber sensory afferent neurons, which contain neuropeptides such as calcitonin-gene related peptide and substance P, mediate a wide variety of physiologic responses, including chemogenic pain, thermoregulation, and neurogenic inflammation. Capsaicin, the pungent constituent in red pepper, functions to activate and then, at higher doses and longer times, desensitize this class of neurons. This latter response provides the basis for the therapeutic application of capsaicin. A major advance in the field has been the identification of resiniferatoxin, a phorbol-related diterpene, as an analog of capsaicin that is ultrapotent but with differential selectivity. In particular, resiniferatoxin is only similar in potency for induction of pain but is much more effective for desensitization. Structure-activity analysis in whole animal experiments provides further evidence for dissociation of biologic endpoints, strongly arguing for the existence of vanilloid receptor subclasses. Using resiniferatoxin, we have been able to define specific, high-affinity receptors for capsaicin both in animal models such as rats and in man. Of great importance, the pharmacologic characterization in cultured dorsal root ganglion cells of the high-affinity resiniferatoxin-binding site and of the physiologic response believed to be directly coupled to the receptor, viz. calcium uptake, differed in structure-activity and in cooperativity. We conclude that multiple high-affinity vanilloid receptor subclasses mediate vanilloid response; moreover, the resiniferatoxin-selective subclass of vanilloid receptors is not the voltage-independent, cation-nonselective ion channel as previously believed. Optimization of ligands for the individual vanilloid receptor subclasses should revolutionize this therapeutic area.
Article
This study compared heartburn severity, number of episodes, and changes in esophageal pH induced by three meals. Symptomatic volunteers consumed the following on different occasions: McDonald's Quarter Pounder, french fries, and chocolate shake; McDonald's Sausage Biscuit with Egg, cheese, raw onion, and chocolate milk; and Wendy's Chili and red wine. Increases in reflux episodes over baseline for the hamburger, sausage biscuit, and chili meals were 28.8 +/- 5.7, 36 +/- 5.5 and 43.7 +/- 8.8, respectively. The sausage biscuit and chili increased reflux compared to the hamburger (P < 0.05), but the chili did not differ statistically from the sausage biscuit meal. Onset and peak heartburn for the hamburger, sausage biscuit, and chili meals were 45 and 90, 30 and 120, and 15 and 150 min, respectively. Despite lower fat content, chili and red wine promoted more reflux and heartburn pain than the other meals, demonstrating the importance of meal selection in provocative meal studies.
Article
The aim of the present study was to investigate local vascular and sensory changes and their correlation in order to obtain a better understanding of the mechanisms of allodynia, hyperalgesia and vascular changes following tissue inflammation induced by repetitive application of capsaicin cream. This type of application was utilized as a controlled model of inflammation which was altered in intensity due to its repetitive applicability. Ten healthy volunteers participated in two experiments separated by at least five days. Each experiment consisted of a baseline session followed by five additional sessions. Before these sessions either 1.5 g capsaicin (1%) or placebo cream was applied to the volar site of the forearm for 15 min. The areas of stroking allodynia and pin-prick hyperalgesia were mapped and the intensity of spontaneous pain (VAS) was assessed after each application of the cream. In addition, the visible flare, temperature (IR-Thermography), and blood- flow (Laser-Doppler) were measured. The first application of capsaicin was perceived as painful; it induced both secondary hyperalgesia and allodynia. Compared to placebo, the first application of capsaicin cream also resulted in an increased blood-flow, elevated temperature and visible flare. The highest values of these sensory and vascular parameters were reached after the third application. A direct correlation between visible flare, secondary mechanical hyperalgesia and allodynia following repetitive application of capsaicin indicates that both common central and peripheral mechanisms were involved in these changes.
Article
Afferent nerves play a major role in the regulation of gastrointestinal motility. The questions remains if specific food ingredients can selectively activate such fibers. The aim of the study was to investigate the effect of intraesophageal application of a capsaicin-containing red pepper sauce (Tabasco) suspension on upper gastrointestinal motility in a controlled trial. After a baseline recording [esophageal motility, balloon distension, electrogastrogram (EGG)], red pepper or saline solution was infused intraesophageally in seven healthy volunteers. At 30 min gastric emptying and orocecal transit time were determined using a [13C]acetate and H2-lactulose breath test. Infusion of red pepper sauce suspension significantly increased the amplitudes (65.8 +/- 3 to 78.5 +/- 4.7 mm Hg, P < 0.05) and propagation velocity (2.9 +/- 0.3 to 4.25 +/- 0.3 sec, P < 0.05) of esophageal pressure waves and LES pressure (17.8 +/- 1.4 to 23.7 +/- 2.6 mm Hg, P < 0.05). It significantly decreased perception and discomfort threshold of intraesophageal balloon distension, reduced the percentage of normal electrical activity in the EGG, and delayed gastric emptying (saline: T(1/2) 42.9 +/- 12.0 min vs red pepper: T(1/2) 66.8 +/- 19.0 min, P < 0.05). Despite the prolongation of gastric emptying, orocecal transit time was not altered, indicating an actual increase of intestinal transit. Esophageal application of capsaicin-containing red pepper sauce suspension had profound changes on upper gastrointestinal motility, which could improve clearance and protection of the esophagus and could lead to retention of the irritant in the stomach and faster transit through the small bowel.
Article
Chilli and its pungent ingredient, capsaicin, have been shown to protect against experimental gastric mucosal injury induced by various necrotizing agents such as ethanol and aspirin and stress. We investigated the effect of capsaicin and long-term ingestion of chilli on haemorrhagic shock-induced gastric mucosal injury in the rat. Anaesthetized male Sprague-Dawley rats were subjected to haemorrhagic shock by withdrawing blood to reduce the mean arterial blood pressure to 30-40 mmHg with subsequent reinfusion of shed blood. This resulted in gastric mucosal injury with readily identifiable haemorrhagic lesions. Capsaicin (5 mg) administered prior to, but not after, haemorrhagic shock, significantly reduced the gastric mucosal injury in intact animals. Sensory ablation with capsaicin pretreatment (125 mg/kg bodyweight) abolished the gastroprotective effect afforded by capsaicin. Similarly, 4 week intake of chilli powder (360 mg daily) reduced the gastric mucosal injury in intact, but not in capsaicin-desensitized rats. Capsaicin and long-term chilli intake protected against haemorrhagic shock-induced gastric mucosal injury and the protection may be mediated by capsaicin-sensitive afferent neurons. Our studies are of potential significance in the context of stress ulcer disease in the human.
Article
Psychophysical methods were used to assess changes in the intensity of irritant sensations elicited by repeated application of capsaicin and nicotine delivered unilaterally to the tongue of human subjects. Whereas capsaicin (0.5 or 3 p.p.m.; repeated at 1 min intervals over 10 min) evoked progressively stronger ratings of irritation (sensitization), there was a significant decrement in irritation ratings (desensitization) to repeated application of nicotine (0.1%). A two-alternative forced-choice (2-AFC) procedure was additionally used to test for self-and cross-desensitization. After the subjects had received either repeated capsaicin or nicotine, a rest period ensued followed by the 2-AFC procedure. Either capsaicin or nicotine was delivered bilaterally to the tongue and subjects were asked to choose which side yielded a stronger sensation. Following capsaicin pretreatment, subjects reported that capsaicin evoked a stronger sensation on the previously untreated side (capsaicin self-desensitization). Similar self-desensitization was observed with nicotine. Furthermore, nicotine evoked a significantly weaker sensation on the side of the tongue pretreated with capsaicin (cross-desensitization). In contrast, capsaicin did not consistently evoke a weaker sensation on the nicotine-pretreated side, indicating an absence of cross-desensitization. These results are discussed in terms of physiological mechanisms that might underlie the contrasting sensory effects of nicotine versus capsaicin.
Article
Numerous factors are important in the pathophysiology of gastroesophageal reflux disease (GERD). The anti-reflux barrier consists of the lower esophageal sphincter (LES) and crural portion of the diaphragm. Absolute LES pressure less than 6 mmHg is required for gastroesophageal reflux (GER), but this is more frequently associated with increased episodes of transient relaxation than persistently low LES pressure. The vast majority of patients with complicated GERD have a hiatal hernia, because the gastric excursion into the chest displaces the LES segment of the distal esophagus above the crural diaphragm, promoting a pinch-cock effect that impairs acid clearance. Clearance of refluxed acid from the esophagus is dependent on gravity, peristalsis and saliva (pH > 6) to neutralize residual acid. Ineffective peristalsis, characterized by low amplitude contractions and dysmotility, represents the major impairment to normal acid clearance. Despite our great attention to these areas, gastric factors may be the most amenable abnormalities to treatment in GERD. Delayed gastric emptying is present in 10-15% of GERD patients, but more subtle postprandial abnormalities may contribute to gastric distension and transient LES relaxation. Although reflux patients are infrequently hypersecretors of acid, studies find acid combined with pepsin to be the most injurious agents to the esophageal mucosa. Recent studies also show increased amounts of bile acids in the refluxate of GERD patients, especially those with Barrett's esophagus. The influence of gastric colonization by Helicobacter pylori is just now being understood. Exciting studies suggest that H. pylori colonization, especially with the more virulent cagA-positive strains, may be protective against severe esophagitis and Barrett's esophagus. Increased intragastric ammonia production and pangastritis with gastric atrophy and intestinal metaplasia, both promoting hypoacidity, are the most likely mechanisms. Conversely, eradication of H. pylori may aggravate GER in some susceptible subjects.
Official method 995.03: Capsaicinoids in capsicums and their extractives
  • AOAC
AOAC. Of®cial method 995.03: Capsaicinoids in capsicums and their extractives. J Assoc Off Anal Chem Int 1996; 79: 738.
Accurate, simple measurement of gastric emptying by 13C-octanoic acid breath test (OBT) in diabetics
  • Js Lee
  • M Camilleri
  • A Zinsmeister
  • D Burton
  • Mg Choi
  • Ks Nair
Accurate, simple measurement of gastric emptying by 13 C-octanoic acid breath test (OBT) in diabetics
  • J S Lee
  • M Camilleri
  • A Zinsmeister
  • D Burton
  • M G Choi
  • K S Nair
Lee JS, Camilleri M, Zinsmeister A, Burton D, Choi MG, Nair KS. Accurate, simple measurement of gastric emptying by 13 C-octanoic acid breath test (OBT) in diabetics. Gastroenterology 1999; 116: A966(Abstract).
Accurate, simple measurement of gastric emptying by 13C-octanoic acid breath test (OBT) in diabetics
  • Lee