Effects of Coffee on the Gastro-Intestinal Tract: A Narrative Review and Literature Update.

The objective of the present research was to review the state of the art on the consequences of drinking coffee at the different levels of the gastrointestinal tract. At some steps of the digestive process, the effects of coffee consumption seem rather clear. This is the case for the stimulation of gastric acid secretion, the stimulation of biliary and pancreatic secretion, the reduction of gallstone risk, the stimulation of colic motility, and changes in the composition of gut microbiota. Other aspects are still controversial, such as the possibility for coffee to affect gastro-esophageal reflux, peptic ulcers, and intestinal inflammatory diseases. This review also includes a brief summary on the lack of association between coffee consumption and cancer of the different digestive organs, and points to the powerful protective effect of coffee against the risk of hepatocellular carcinoma. This review reports the available evidence on different topics and identifies the areas that would most benefit from additional studies.

Role of gastric acid inhibition, prostaglandins and endogenous-free thiol groups on the gastroprotective effect of a proteolytic fraction from Vasconcellea cundinamarcensis latex.

OBJECTIVES: The aim of this study was to extend our knowledge about the mechanism involved in the gastroprotective effect of P1G10, a proteolytic fraction rich in cysteine proteinases from Vasconcellea cundinamarcensis (syn. Carica candamarcensis) latex, which demonstrated gastric healing and protection activities in rats. METHODS: Wistar rats were submitted to gastric lesions by indomethacin and treated with P1G10 (10 mg/kg). Free thiol groups and prostaglandin E2 content were measured in gastric mucosal and gastrin levels in blood samples. To evaluate the participation of nitric oxide (NO) or proteolytic activity of P1G10 on its gastroprotective effect, animals were treated with an inhibitor of NO production (L-NAME) or the fraction inhibited by iodoacetamide, respectively. Gastric secretion study (acidity and pepsin activity) was also performed. KEY FINDINGS: P1G10 (10 mg/kg) inhibited the occurrence of gastric lesions by indomethacin, restored the free thiol groups content on gastric mucosa and increased moderately prostaglandin E2 levels (34%). Furthermore, the treatment decreased the gastrin levels (95%), suggesting a possible modulation of secretory activity. This effect was accordant with attenuation of gastric acidity (42%) and pepsin activity (69%) seen in animals subjected to pyloric ligation. The inhibition of NO production or the proteolytic activity of P1G10 does not affect the gastroprotective effect. CONCLUSIONS: These results can explain the gastroprotective activity of P1G10 and serve a basis for further studies of this active principle.

Gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is one of the most common disorders of the gastrointestinal tract. Over past decades, considerable shifts in thinking about the disease have taken place. At a time when radiology was the only diagnostic test available, reflux disease was regarded as synonymous with hiatus hernia. After the advent of the flexible endoscope, reflux disease was, for a period, equated to oesophagitis. The introduction of oesophageal pH monitoring made us believe that reflux disease could be defined by an abnormally high proportion of time with oesophageal pH less than 4. Moreover, the successive arrival of histamine-2-receptor antagonists and proton-pump inhibitors changed our idea of treatment for the disease, with swings from and towards surgery, endoscopic techniques, and alternative pharmaceutical options.

Radiofrequency energy delivery to the lower esophageal sphincter reduces esophageal acid exposure and improves GERD symptoms: a systematic review and meta-analysis.

PURPOSE: Studies of endoscopic application of radiofrequency energy to the lower esophageal sphincter for gastroesophageal reflux control have produced conflicting reports of its effectiveness. This study aimed to conduct a meta-analysis of randomized controlled trials and cohort studies to assess the impact of this treatment. METHODS: Twenty studies were included. Outcomes analyzed included gastroesophageal reflux disease (GERD) symptom assessment, quality of life, esophageal pH, and esophageal manometry. RESULTS: A total of 1441 patients from 18 studies were included. Radiofrequency treatment improved heartburn scores (P=0.001), and produced improvements in quality of life as measured by GERD-health-related quality-of-life scale (P=0.001) and quality of life in reflux and dyspepsia score (P=0.001). Esophageal acid exposure decreased from a preprocedure Johnson-DeMeester score of 44.4 to 28.5 (P=0.007). CONCLUSIONS: Radiofrequency ablation of the lower esophageal sphincter produces significant improvement in reflux symptoms and may represent an alternative to medical treatment and surgical fundoplication in select patients.

Healthcare seeking in gastro-oesophageal reflux disease: a qualitative study.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common problem in the community, and many patients do not seek medical attention despite potential morbidity and the availability of effective therapeutic interventions. The factors which determine healthcare seeking in GORD are not well understood. AIM: To examine the symptom experience and health and illness beliefs in people with GORD, who had either been diagnosed with the condition, or were dealing with the symptoms themselves. METHODS: A total of 12 focus groups and 65 face-to-face interviews were conducted in the USA, UK, France and Germany, and involved 164 participants, who had either been diagnosed with GORD or were identified as having GORD in the community, using a random digit dialling telephone method. Transcripts of focus groups and interviews were analysed thematically, using a constant comparative approach, to identify key factors associated with healthcare seeking. RESULTS: Patients' descriptions of GORD symptoms were often vivid, with the use of unexpected imagery and unusual beliefs about causality. We were able to identify four factors associated with healthcare seeking for GORD which were: the characteristics of symptoms (intensity and control), the perceived seriousness of symptoms, interference by symptoms with daily life and views about medicines and the medical profession. CONCLUSION: Patients with GORD, using both self care and formal medical care, have a surprising range of ideas about the causes and best treatments of their symptoms. Physicians' awareness of these beliefs, coupled with an understanding of the factors associated with healthcare seeking for GORD, is likely to be important in enhancing clinical management and in patient and public education.

Antioxidant activity of commercial soft and hard wheat (Triticum aestivum L.) as affected by gastric pH conditions.

Phenolic compounds from soft and hard wheat and their milling fractions were extracted into distilled deionized water, and their in vitro antioxidant activities were evaluated. Wheat samples were used as such (nontreated) or subjected to pH adjustment (treated) in order to simulate gastrointestinal pH conditions. The total phenolic content (TPC) was determined using Folin-Ciocalteu's procedure. The total antioxidant activity (TAA) was determined using Trolox equivalent antioxidant capacity assay and expressed as Trolox equivalents. The antioxidant activity of wheat extracts was also evaluated using the beta-carotene bleaching assay, scavenging of 2,2-diphenyl-1-picrylhydrazyl radical, and inhibition of oxidation of human low density lipoprotein cholesterol. The TPC, TAA, and antioxidant potential, evaluated using different methods of wheat samples, were significantly increased following gastrointestinal tract-simulated pH changes. Thus, digestion taking place in the gastrointestinal tract in vivo may also enhance the antioxidant properties of the extracts.

[Herbs and herbal preparations applied in the treatment of gastric hyperacidity, gastric and duodenal ulcer in cigarette smokers]. / Surowce i preparaty roslinne stosowane w leczeniu choroby wrzodowej zoladka i dwunastnicy u palaczy tytoniu.

The origins of gastric hyperacidity, gastric and duodenal ulcer appearance includes genetic predisposition, incorrect diet and unbalanced lifestyle, e.g. increased stress level, cigarette smoking. Herbal drugs have been proved to be very effective in treatment of hyperacidity, gastric and duodenal ulcer. They can be applied as drugs supplementing or enhancing the activity of synthetic medicines. Moreover, herbal drugs have been successfully applied inprophylactic of hyperacidity, gastric and duodenal ulcer. Herbal therapeutic preparations are administered as infusions from individual herbs, from mixtures of herbs, tinctures, herbal preparations. The most often used herbs include mucus: Lini semen, Psylli semen, Foenugraeci semen, Althaeae radix/folium, Sinapis albae semen; antiphlogistic volatile-oils: Chamomillae anthodium, Millefolii herba, moreover Glycyrrhizae radix, Aloe gel.

A novel pH-dependent gradient-release delivery system for nitrendipine II. Investigations of the factors affecting the release behaviors of the system.

Nitrendipine, a dihydropyridine calcium antagonist, was used as a poorly water-soluble model drug. To improve its dissolution rate and extend the therapeutic period in vivo as well, a novel pH-dependent gradient-release drug delivery system for nitrendipine having a solid dispersed matrix structure was developed. Four factors, i.e. the amount of excipients, the pH of the dissolution medium, the rotating speed of the paddle of the dissolution apparatus and the particle size of the microspheres, all of which affect the drug-release behavior of the pH-dependent microspheres of the system were investigated in detail. The release profiles of the pH-dependent drug delivery system under simulated gastrointestinal tract pH conditions were also investigated. The results showed that the release rate of drug from the microspheres increased on increasing the amount of respective pH-dependent polymers formulated. Due to the fact that the active drug was incorporated in pH-dependent polymers and was present in a solid dispersion state in the microspheres, the release rate of the drug from the microspheres depended on the dissolution rate of the polymers, which was mainly influenced by the pH of dissolution medium, whereas the rotating speed of the paddle and the particle size of the microspheres had only a relatively minor effect. The release behavior of the system under simulated gastrointestinal tract conditions exhibited obvious gradient-release characteristics, showing that the release rate of the active drug could be controlled efficiently before the microspheres reached the appropriate region of the gut for absorption. These findings suggest that the pH-dependent drug delivery system could be fabricated by using present microspheres.

Effect of digestive site acidity and compatibility on the species, lipopily and bioavailability of iron, manganese and zinc in Prunus persica Batsch and Carthamus tinctorus.

The effects of compatibility, that is combination of Prunus persica Batsch (L.) and Carthamus tinctorus (L.), and different acidity of digestive site on the species, lipopily and bioavailability of coordinated complex of iron, manganese, and zinc in medical decoction were studied. In view of octanol, a long-chain alkanol, resembled as the configuration of carbohydrate and adipose in human body, the octanol- and water-solubility were used to define the species of trace element in phytomedicine, to identify the lipopily and bioavailability of trace element, and octanol-water system was adopted to study the distribution of trace element in decoction of P. persica Batsch (L.) (A), C. tinctorus (L.) (B), and combination of medicine A and B (C) in stomach and intestine. The total concentration, water- and octanol-solubility concentration of iron, manganese, and zinc in medicinal material A, B and C or its decoction under gastric and intestinal acidity, were determined respectively by flame atomic absorption spectrometry, analyzed and compared. The compatibility of medicine A and B enhances the extract percent, octanol-solubility concentration, and stability of coordinated complex of iron, manganese, and zinc. Different acidity of digestive site and compatibility of medicines impact on the ligands of iron, manganese, and zinc, then greatly affect the species and its quantification, the lipopily and bioavailability of trace element. Such influence is quite different for different trace element. Such factors, especially the concentration of octanol-solubility trace element, could be the basis of the dosage to avoid trace element overload.

Characteristics of the gastric pH profiles of unfed and fed cynomolgus monkeys as pharmaceutical product development subjects.

Gastric pH is an important factor which significantly affects the dissolution of drugs, and therefore their bioavailability. In this study, the gastric pHs were measured directly with a miniature pH electrode inserted through the nostril into the body of the stomach of cynomolgus monkeys. Results from three separate sets of measurements using the same male monkeys indicated that the median gastric pH profiles of unfed monkeys were low, fluctuating between pH 1 and pH 3. However, the median gastric pHs in fed monkeys given about 108 g of a biscuit-type solid food, which are commonly provided, shifted toward a more neutral range between pH 5 and pH 7, and remained in this range for about 9 h. This result contrasted with reported results for humans after eating a standard meal, which showed a neutral range between pH 5 and pH 7 for a brief period. Consequently, these results indicate that although the gastric pH of unfed cynomolgus monkeys is similar to that of fasting humans, there is a great difference in the gastric pH profiles between humans and monkeys after eating, which suggests that further studies are needed to establish optimal feeding conditions for bioavailability studies in monkeys.

Inhibition of carbachol stimulated acid secretion by interleukin 1beta in rabbit parietal cells requires protein kinase C.

BACKGROUND: Interleukin 1beta (IL-1beta) is a potent inhibitor of gastric acid secretion. Regulatory actions at several levels have previously been demonstrated, including direct inhibition of parietal cell acid secretion. Although IL-1beta may activate several intracellular signalling pathways, the mechanisms responsible for inhibition of carbachol stimulated acid secretion have not been determined. AIMS: To investigate the roles of protein kinase C (PKC) and the sphingomyelinase signalling pathways in the regulation of acid secretion by IL-1beta. METHODS: Rabbit parietal cells were obtained by collagenase-EDTA digestion and centrifugal elutriation. Acid secretion stimulated by carbachol and A23187 (to mimic elevations in intracellular calcium) was assessed by 14C aminopyrine uptake in response to IL-1beta, PKC, and sphingomyelinase manipulation. RESULTS: IL-1beta inhibited carbachol and A23187 stimulated acid secretion in a dose dependent manner. The inhibitory actions were completely reversed by each of three different PKC inhibitors, staurosporine, H-7, and chelerythrine, as well as by PKC depletion with high dose phorbol ester pretreatment. IL-1beta did not downregulate parietal cell muscarinic receptor. IL-1beta significantly increased membrane PKC activity. Activation of the sphingomyelinase/ceramide pathway had no effect on basal or stimulated acid secretion. The inhibitory action of IL-1beta was independent of protein kinase A and protein kinase G activity. CONCLUSIONS: IL-1beta directly inhibits parietal cell carbachol stimulated acid secretion. This action occurs distal to muscarinic receptor activation and elevations in intracellular calcium and requires PKC.

Maximal acid reflux control for Barrett's oesophagus: feasible and effective.

UNLABELLED: The treatment of patients with Barrett's oesophagus is controversial. Debate exists regarding the use and value of high dose acid suppression as the standard of practice. Despite prolonged use of high dose proton pump inhibitors (40 mg omeprazole, 60 mg lansoprazole), most studies have shown no convincing evidence of significant regression of Barrett's length. These studies, however, have used fixed doses of proton pump inhibitors and did not regularly document control of oesophageal acid exposure. AIM: To determine whether regression of Barrett's epithelium can be achieved with documented maximal acid suppression. METHODS: We have prospectively followed nine patients with Barrett's oesophagus (eight male; mean age 60 years) for more than 1 year. They were all treated using medical therapy with pH monitoring documenting oesophageal acid exposure over 24 h < 1.6% of the time, and with two or more esophagogastroduodenoscopies performed by the same endoscopist. RESULTS: Acid control was individually tailored and achieved with proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) and ranitidine at bedtime (HS) (Ran) if necessary. All nine patients (100%) showed some evidence of regression. All nine patients (100%) showed a decrease in Barrett's length (mean 2 cm, range 1-3 cm). Six out of nine (66.67%) patients showed evidence of squamous islands on the last oesophagogastroduodenoscopy. The mean total distal oesophageal acid exposure was 0.38% (range: 0-1.5%). The mean follow-up of patients was 54 months (range: 13-118 months). CONCLUSIONS: Consistent and individually tailored maximal acid suppression documented by pH-metry is achievable and may result in decreased length and development of squamous islands in patients with Barrett's epithelium. This approach should be further evaluated as potentially the preferred medical treatment for these patients.

Acid-induced gastric damage in rats is aggravated by starvation and prevented by several nutrients.

The aggravation of acid-induced gastric damage and its prevention by glucose, ascorbate or glutathione precursors was studied in fed and food-deprived rats. The stomachs of fed rats and those starved for 1, 3 or 5 d were vagotomized just before irrigating for 3 h with solutions containing 0-150 mmol HCI/L. Mucosal glutathione, mucus, lipid peroxides and acid back-diffusion were measured. Stomach ulcers were evaluated by morphological and histological examination. The preventive effects of glucose, ascorbate and a mixture of L-glutamine, L-glycine and L-cysteine were evaluated in the stomachs of rats that were starved for 5 d, vagotomized, then perfused for 3 h with 100 mmol HCI/L. Greater acid back-diffusion and ulcer formation, and lower glutathione and mucus levels in starved rats were dependent on the duration of starvation and luminal acidity. Increased acid back-diffusion and decreased glutathione and mucus production were negatively correlated (r < -0.80, P < 0.05) with ulcer formation. A significant enhancement in mucosal lipid peroxide concentration and serious damage of forestomach and corpus mucosal cells were observed in starved rats exposed to 100 mmol HCI/L. These ulcerogenic factors were effectively inhibited in acid-perfused stomachs of food-deprived rats by daily intraperitoneal injection of the amino acid mixture (150 mg/kg) or by an average daily consumption via drinking water of glucose (10 g) or ascorbate (1.2 g). Starvation aggravated acid-induced gastric damage and was associated with greater acid back-diffusion and oxygen radical generation, and lower mucosal glutathione and mucus production.

Emulsification and lipolysis of triacylglycerols are altered by viscous soluble dietary fibres in acidic gastric medium in vitro.

This in vitro study was designed to test the hypothesis that soluble dietary fibres can alter the process of intragastric lipid emulsification and possibly subsequent triacylglycerol lipolysis. Three guar gums, two pectins and gum arabic were dissolved in acidic gastric medium in the concentration range 0.3-2.0% (w/v). Viscosities of fibre solutions were measured and apparent viscosities varied over a wide range (0.7-77 mPa/s). Emulsification of a lipid mixture (triolein/phosphatidylcholine/cholesterol) was performed under mild conditions in the presence of increasing concentrations of soluble fibres. The amount of emulsified lipid was not affected whereas the size of the emulsified droplets was increased by raising the concentration of viscous fibres only. The droplet size (r=0.75, P=0.006) and overall droplet surface area (r=-0.69, P=0.009) were strongly correlated with the medium viscosity in the range 0-20 mPa/s. The addition of solutions of viscous fibres to a preformed standard emulsion did not change the initial velocity of human gastric lipase reaction. Conversely, when emulsions prepared in the presence of fibres (i.e. with different droplet sizes) were incubated with excess gastric enzyme for 2 h, the high-viscosity guar gum significantly reduced the extent of triacylglycerol lipolysis, as compared with control and low- or medium-viscosity fibres. In conclusion, the data obtained show that reducing emulsification of dietary lipids in the mildly acid medium found in the stomach is a mechanism by which soluble viscous fibres can alter lipid assimilation.

Low gastric hydrochloric acid secretion and mineral bioavailability.

Young infants and approximately 30% of the elderly have low secretion of hydrochloric acid by gastric parietal cells. It has been established that low hydrochloric acid secretion can lead to decreased absorption of ferric iron. Conflicting results have been obtained in clinical studies of the effects of intraluminal gastric pH values on calcium absorption. The results of an in vitro study suggest that the chemical form of the ingested calcium and the presence of protein may influence whether high intraluminal gastric pH values affect resultant calcium solubilities in the small intestine. The effects of low hydrochloric acid secretion on zinc absorption have not been ascertained. The results of an in vitro study indicate that high intraluminal gastric pH values would not affect resultant zinc solubilities in the small intestine following pancreatin digestion of soy protein isolate supplemented with calcium and/or zinc. Considering that the diets of many elderly contain primarily plant foods and that soy protein isolate formulas are commonly fed to infants, further research is especially needed to determine the effects of low hydrochloric acid secretion on mineral bioavailabilities from high fiber and phytate containing plant foods.

Neural reflex of the canine pylorus to intraduodenal acid infusion.

In 29 chloralose-urethane anesthetized dogs, a manometric assembly was inserted through a gastrostomy to monitor pressure of the pyloric region with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric sideholes and serosal strain gauges. An additional tube channel allowed intraduodenal infusions 1-2 cm aborad from the pylorus. Intraluminal infusion of hydrochloric acid (0.1 N, 0.92 ml/min, for 2 min) reproducibly caused activation of motor activity in the pyloric region and peristaltic duodenal activity. Proximal duodenal activity probably contributed to the total phasic response recorded in the pylorus region. Excitatory responses could also be elicited by infusion of phenyl-biguanide (stimulant of sensory nerve endings), but not by control infusions with diluent (Krebs' buffer or saline). The motor response of the pyloric region to intraduodenal acid was blocked by intraduodenal application of 2% xylocaine. Atropine (30 micrograms/kg i.v. and 100 micrograms i.a.) or hexamethonium (10 mg/kg and 1 mg i.a.) markedly reduced or blocked the acid-induced pyloric motor response of this region but propranolol (1.0 mg/kg i.v. and 100 micrograms i.a.), phentolamine (1.5 mg/kg i.v. and 100 micrograms i.a.), or naloxone (200 micrograms/kg and 20 micrograms i.a.) had no effect. We believe these observations show the existence of a reflex from the duodenum to the pylorus in response to intraluminal stimuli mediated by a chain of cholinergic nerves. In the dog, endogenous opioid peptides do not contribute to the excitatory reflex pathway activated by intraduodenal acid or phenyl-biguanide. As intraluminal acid in the duodenum activates this reflex, it may play a role in the physiologic and pathophysiologic role of gastric emptying in this species.

Immunogenicity in guinea pigs and tolerance in grass pollen-sensitive volunteers of enteric-coated grass pollen allergens.

An acid-insoluble, methacrylic acid, methyl methacrylate copolymer (Eudragit L-100) was used to give an enteric coating to a grass pollen extract in order to protect it against gastric degradation. Substantial protection against the degradative effects of simulated gastric secretion was demonstrated using this preparation which was well tolerated by grass pollen-allergic volunteers. The enteric-coated allergen induced a greater secondary antibody response than did an aqueous presentation when administered orally to guinea pigs which had been primed previously by subcutaneous injection. This result indicates that an effective hyposensitisation regimen could consist of a short series of initial parenteral injections, followed by an oral course of the protected allergen.