Small doses of the unabsorbable substance polyethylene glycol 3350 accelerate oro-caecal transit, but slow gastric emptying in healthy subjects.

BACKGROUND: Polyethylene glycol 3350 increases stool frequency and accelerates colonic transit. Used as a laxative, it proved effective in patients with normal and slow transit. Although free of severe side effects, it may cause nausea and vomiting. The effect of this substance on upper gut transit has not been studied. AIM: To investigate the effect of polyethylene glycol 3350 on gastric emptying and oro-caecal transit in 12 healthy subjects. METHODS: In a randomised controlled study, isosmotic polyethylene glycol 3350 electrolyte balanced solution, in the maximal recommended dose or isosmotic electrolyte solution, was administered after breakfast and lunch on separate days. Gastric half-emptying time and oro-caecal transit time were measured using [13C]-octanoate and lactose-[13C] ureide breath tests. RESULTS: Isosmotic polyethylene glycol 3350 electrolyte solution, as compared to isosmotic electrolyte solution, decreased oro-caecal transit time from 424+/-28 to 314+/-17 min (P = 0.001). Gastric half-emptying time was significantly increased (84+/-6 min versus 127+/-14 min; P = 0.006). CONCLUSION: Polyethylene glycol 3350 accelerate oro-caecal transit in healthy subjects, but also cause an important delay in gastric emptying. The delay in gastric emptying may be of clinical significance in patients who have associated gastroparesis.

Influence of continuous isobaric rectal distension on gastric emptying and small bowel transit in young healthy women.

Patients with slow transit constipation frequently have delayed gastric emptying. In animals rectal distensions inhibit gastrointestinal motility. In healthy volunteers isovolumetric rectal distensions delay upper gut transit. The purpose of this study was to determine the effect of continuous isobaric rectal distension on gastric emptying and oro-cecal transit in young females. Using validated 13C octanoic and lactose-[13C] ureide breath tests gastric half-emptying time and oro-cecal transit time for a meal were measured in 12 volunteers. The tests were repeated in randomized order: during isobaric balloon distension and during sham distension. Isobaric rectal distension was applied using a polyethylene bag connected to a barostat. Intraballoon pressure was kept just below the threshold for the urge sensation. Mean gastric half-emptying time during rectal distension (92.3 +/-5.1 min) was significantly higher than during sham distension (78.8 +/- 4 min; P = 0.015). Mean oro-cecal transit time during rectal distension (391.3 +/-29.1 min) and sham distension (328.8 +/- 38.4 min) were not significantly different. In conclusion, these findings indicate that isobaric rectal distension inhibits gastric emptying, but not small bowel transit in young healthy women. Studies in patients with constipation are indicated.

Measurement of hepatic and intestinal CYP3A4 and PGP activity by combined po + iv [14C]erythromycin breath and urine test.

The aim of the present study was to develop a test for measuring hepatic and intestinal removal of cytochrome p-450 3A4 (CYP3A4)- and P-glycoprotein (PGP)-dependent xenobiotics that would be applicable for clinical use in humans. Orally and intravenously administered [N-methyl-14C]erythromycin was used for evaluation of 14C-labeled excretion dynamics in breath and urine. Simultaneous breath and urine test measurements were performed in 32 healthy volunteers and in 23 renal transplant recipients. Mathematical analysis of the excretion rate of labeled CO2 in breath and labeled carbon in urine resulted in 1). separation of both CYP3A4 and PGP activity in the liver and the intestinal mucosa and 2). numerical calculation of the dynamics of the different processes. The test was sufficiently sensitive to detect theoretically predicted process-specific pharmacological modulations by different drugs in healthy volunteers and after recent renal transplantation. It is concluded that the combined oral and intravenous erythromycin breath and urine test is a reliable and noninvasive test to measure phenotypic intestinal and hepatic CYP3A4 and PGP activity and may be a promising tool for prediction of drug interactions and dose adjustment of many pharmacotherapeutics in clinical practice, e.g., immunosuppressive agents after renal transplantation.

In vivo influence of nicotine on human basal and NSAID-induced gut barrier function.

BACKGROUND: Smoking reduces the non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal permeability increase in healthy people. It also affects inflammatory bowel disease that is associated with a disturbed gut barrier function. To assess the role of nicotine on barrier function, its influence on basal and NSAID-induced intestinal permeability was studied in healthy volunteers. METHODS: Thirty-one healthy non-smoker subjects performed permeability tests with 51Cr-EDTA and sugar markers (sucrose, lactulose, mannitol, sucralose) before and during 2 weeks of nicotine patch application, and with and without indomethacin intake, respectively. Since smoking has been described as affecting motility, transit measurements were also done with the sodium[13C]-octanoate and lactose-[13C]-ureide breath tests before and during nicotine exposure. Correlations between permeability markers were checked and the influence of gastrointestinal transit was assessed. RESULTS: Nicotine did not affect barrier function in vivo, nor gastric emptying, small-bowel transit time or orocaecal transit. 51Cr-EDTA and lactulose correlated in basal 0-6 h permeability testing (r = 0.529, P < 0.0001), as did 6-24 h excretion of 51Cr-EDTA and sucralose (r = 0.474, P < 0.001); 97% and 90% of the subjects had a permeability increase after indomethacin intake for 0-6 h and 6-24 h excretion of Cr-EDTA, respectively. This population proportion is 63% for lactulose/mannitol and 83% for sucralose. CONCLUSIONS: Short-term exposure to nicotine does not alter normal basal or NSAID-induced gut barrier function or transit. 51Cr-EDTA and the respective sugar markers correlate well in in vivo permeability testing in healthy humans. The radioactive test detects more NSAID-induced permeability increase than does the lactulose/mannitol ratio permeability test.

Oxidative breakdown of octanoic acid is maintained in patients with cirrhosis despite advanced disease.

As an octanoic acid 13CO2 breath test is frequently used to test gastric emptying of solid food, the purpose of the present study was to study whether oxidative breakdown of octanoic acid is affected by severe liver disease. The design of our study was twofold. First, cirrhotic patients (n = 82) of varying severity were compared with healthy controls (n = 17). Values of half-time, time point of maximal expiration and cumulative recovery of octanoic acid breath tests (OBT) were not significantly different between them. Secondly, cirrhotic patients (n = 10) were studied before placement of transjugular intrahepatic portosystemic shunt, 4-7 days later and 1-2 months later. Values of half-time, time point of maximal expiration and cumulative recovery of consecutive OBTs did not change significantly. The OBT may therefore be a suitable test in the future to detect delayed gastric emptying of solids in cirrhotic patients with reduced liver function and portal hypertension.

Magnesium chloride slows gastric emptying, but does not affect digestive functions.

BACKGROUND: An inverse relationship has been established between serum magnesium and serum lipid levels. By means of breath tests, we tested the hypothesis that magnesium inhibits intraluminal lipid digestion and subsequently causes changes in lipid metabolism. We also investigated the influence of the administration of magnesium chloride on protein digestion and gastric emptying. METHODS: Five healthy volunteers performed simultaneous breath tests for gastric emptying and intraluminal lipid digestion, and six others for gastric emptying and protein digestion. Each test was performed in basal conditions and after the intake of 800 mg of magnesium chloride dissolved in water. Breath samples were taken at regular time intervals and analysed for 13CO2 and 14CO2 enrichment in order to calculate gastric emptying and lipid and protein digestion rates. RESULTS: The oral administration of a single dose of magnesium chloride resulted in a diminished rate of intraluminal lipid and protein digestion. The most pronounced effect of magnesium chloride, however, was a decreased gastric emptying rate of both test meals. After correction for gastric emptying, no differences were noted in intraluminal lipid or protein digestion. Therefore, the lower lipid levels noted after magnesium supplementation are unlikely to be the result of altered lipid assimilation. CONCLUSION: Magnesium chloride slows gastric emptying but does not influence lipid digestion.

13C mixed triglyceride breath test: a noninvasive method to assess lipase activity in children.

BACKGROUND: Results from the 13C mixed triglyceride (MTG) breath test correlate with duodenal lipase activity in adults. This noninvasive test is a potential screening and diagnostic tool for children with fat malabsorption. The aim of this study was to adapt the methodology of the MTG breath test to study test meals and sampling methods and to define normal values for healthy children of all age groups; premature and full-term infants have similar pancreatic lipase deficiencies. METHODS: After parental consent was obtained, 12 premature infants (< 37 weeks gestation and with body weights > 2 kg), 12 full-term infants (1-6 months old), 20 children (3-10 years old), and 20 teenagers (11-17 years old) were tested. All children were thriving well, had no gastrointestinal or respiratory problems, and had not received any medication that contained natural 13C. For the premature and full-term infants, a formula was prepared that had a low and stable natural 13C content mixed with 100 mg 13C-labeled MTG (1,3-distearyl, 2-[13C-carboxyl] octanoyl glycerol) and 1 g polyethylene-glycol 3350. The best accepted test meal for children over 3 years old was a slice of white bread with 5 g butter and 15 g chocolate paste, mixed with 250 mg 13C-labeled MTG, and a glass of 100 mL whole-fat milk. Children over 3 years old were able to blow through a straw in a vacutainer for collecting the breath samples. In children under 3 years old, expired air was collected by aspirating breath via a nasal prong. Carbon dioxide production was calculated according to weight, age, and sex. RESULTS: For healthy pediatric control participants, the mean values for cumulative excretion of 13CO2 as a percentage of the administered dose after 6 hours were 23.9 +/- 5.2% in premature infants, 31.9 +/- 7.7% in full-term infants, 32.5 +/- 5.3% in children, and 28.0 +/- 5.4% in teenagers. The mean value for healthy adults is 35.6% with a lower reference limit of 22.8%. CONCLUSIONS: Age-specific test meals and breath-sampling techniques for the MTG breath test were defined. The mean values for different age groups may serve as guidelines for normal values in the pediatric population. The cumulative values for expired 13CO2 were above the lower limit for adults, which suggests that preduodenal lipases compensates for pancreatic lipase deficiency in premature and full-term infants.

Lactose-[13C]ureide breath test: a new, noninvasive technique to determine orocecal transit time in children.

BACKGROUND: The lactose-[13C]ureide breath test (LUBT) is a novel, noninvasive test to determine orocecal transit time. Lactose ureide resists the action of brush border enzymes and is metabolized by colonic bacteria. The purpose of the present study was to adapt this breath test for children of various age groups and to determine whether it can be applied in infants, newborns, and preterms to study the development of small intestinal motility. METHODS: In a group of 20 children (3-17 years) in vitro stool analysis and in vivo LUBT results were compared. From each subject a blank stool sample and a sample produced after induction with unlabeled lactose ureide were incubated with 10 mg lactose-[13C]ureide in small, closed bottles. Ten-milliliter CO2 samples were aspirated from the bottles using a needle and a syringe every 30 minutes for 24 hours. All children performed the breath test after induction of 500 mg unlabeled lactose ureide three times the prior day. A liquid test meal (chocolate milk) with 250 mg lactose-[13C]ureide was ingested. Breath samples were collected every 15 minutes for 10 hours. In a second group of 32 children (age range, 0-3 years) consisting of 6 children between 1 and 3 years of age, 6 infants between 6 and 12 months, 13 infants between 0 and 6 months, and 7 preterm infants, only the in vitro stool analysis was performed. Stools were collected for stool incubation, as described. RESULTS: The mean orocecal transit time in the group of 20 children aged 3 to 17 years was 255 minutes (range, 165-390 minutes). Stool incubations demonstrated a clear 13CO2 peak in all infants aged more than 8 months, indicating that their colonic bacterial enzymic activity hydrolyses lactose ureide. However, in all infants aged less than 6 months and in preterm infants, the 13CO2 signal was absent, indicating that those subjects were unable to hydrolyze lactose ureide. CONCLUSION: Infants aged less than 6 months do not host the appropriate bacterial enzymic activity for splitting lactose ureide. The authors conclude that the LUBT can be applied in infants aged more than 8 months, after weaning to solid foods, to determine orocecal transit time.

The effects of smoking and indomethacin on small intestinal permeability.

BACKGROUND: Smoking modulates inflammatory bowel disease, protecting from ulcerative colitis on the one hand and worsening the course of Crohn's disease on the other. This influence might occur through changes in intestinal permeability, because permeability is increased in most patients with Crohn's disease. AIM: To study the influence of smoking on small intestinal permeability and its increase induced by indomethacin. METHODS: 50 smokers and 50 nonsmokers underwent a 51Cr-EDTA basal permeability test and the same test after challenge with indomethacin 125 mg p.o. RESULTS: Small intestinal permeability was the same in smokers (median 1.22%; IQR 1.00-1.58) and nonsmokers (1.24%; 0.94-1.66). Basal small intestinal permeability was lower in females (1.09%; 0.87-1.33) than in males (1.48%; 1.18-1.88). Indomethacin challenge increased permeability by 110% (71-141) in smokers, vs. 156% (78-220) in the nonsmokers (P=0.04). CONCLUSION: Smoking reduces the effect of NSAID on small intestinal permeability. It is therefore unlikely that the adverse effect of smoking on Crohn's disease is related to its influence on intestinal permeability.

13C-egg white breath test: a non-invasive test of pancreatic trypsin activity in the small intestine.

BACKGROUND: The recent availability of egg white protein highly enriched with (13)C has allowed breath test technology to be adapted for the study of protein digestion and absorption. Pancreatic trypsin is considered to be the key enzyme in the proteolytic cascade. AIM: To evaluate trypsin activity in the small intestine of healthy volunteers and patients with pancreatic disease by a recently developed (13)C-egg white breath test. METHODS: A total of 48 healthy volunteers and 30 patients with pancreatic disease were studied after ingestion of a test meal consisting of 22 g (13)C-labelled egg protein. Breath samples were taken before and after ingestion of the meal and analysed for (13)CO(2) concentration. Moreover, pancreatic trypsin output after maximal stimulation was measured in 13 patients and nine healthy volunteers. RESULTS: The six hour cumulative (13)CO(2) excretion in breath was significantly lower in patients than controls (mean (SEM): 6.23 (0.82)% v 19.16 (0. 58)%, p<0.0001). An excellent correlation was found between the six hour cumulative (13)CO(2) excretion and trypsin activity after maximal pancreatic stimulation. CONCLUSION: The non-invasive (13)C-egg white breath test is promising as an indirect pancreatic proteolytic function test.

Differences in gastric motor activity in renal transplant recipients treated with FK-506 versus cyclosporine.

BACKGROUND: Little is known concerning gastric motility after renal transplantation and on the impact of immunosuppressants on gastric emptying. METHODS: Gastric emptying was measured in renal transplant recipients, taking different immunosuppressive therapy (steroids and cyclosporine/azathioprine/FK-506), and compared with normal volunteers. RESULTS: After renal transplantation, gastric emptying of liquids was normal, irrespective of the type of immunosuppression. However, solid gastric emptying was significantly faster in FK-506-treated patients compared with patients taking cyclosporine for all measured emptying parameters. Compared with normal volunteers solid gastric emptying was slower in patients taking cyclosporine, comparable in azathioprine treated patients, and characterized by an unusual short lag phase in patients taking FK-506. CONCLUSIONS: In stable renal transplant recipients gastric emptying of solids was significantly faster in patients on FK-506 compared with patients taking cyclosporine. Therefore, FK-506 may be the immunosuppressant of choice after solid organ transplantation in patients with problems related to gastroparesis.

Amount and fate of egg protein escaping assimilation in the small intestine of humans.

Studies attempting to evaluate protein assimilation in humans have hitherto relied on either ileostomy subjects or intubation techniques. The availability of stable isotope-labeled protein allowed us to determine the amount and fate of dietary protein escaping digestion and absorption in the small intestine of healthy volunteers using noninvasive tracer techniques. Ten healthy volunteers were studied once after ingestion of a cooked test meal, consisting of 25 g of (13)C-, (15)N-, and (2)H-labeled egg protein, and once after ingestion of the same but raw meal. Amounts of 5.73% and 35.10% (P < 0.005) of cooked and raw test meal, respectively, escaped digestion and absorption in the small intestine. A significantly higher percentage of the malabsorbed raw egg protein was recovered in urine as fermentation metabolites. These results 1) confirm that substantial amounts of even easily digestible proteins may escape assimilation in healthy volunteers and 2) further support the hypothesis that the metabolic fate of protein in the colon is affected by the amount of protein made available.

Validation of the lactose-[13C]ureide breath test for determination of orocecal transit time by scintigraphy.

UNLABELLED: The breath test using oral administration of a 13C-labeled substrate, lactose-ureide (LU), to measure orocecal transit time (OCTT) was validated against 99mTc-scintigraphy. Although LU is not absorbed in the human small intestine, colonic bacteria readily metabolize LU, producing 13C-labeled CO2. The time at which 13CO2 appears in breath corresponds to the OCTT. METHODS: Twenty-two healthy volunteers ingested a meal labeled with 99mTc and 13C-LU. Scintigraphy was performed over 8 h at time intervals of 10 or 15 min. OCTT with scintigraphy was defined as the time at which at least 10% of the label had entered the colon. Breath samples were obtained every 10-15 min for 10 h and measured by isotope ratio mass spectrometry. OCTT was defined as the time of first significant increase above baseline. The results were compared using correlation and Altman-Bland statistics. RESULTS: OCTT results from scintigraphy (mean OCTT = 283+/-53 min) and breath test (mean OCTT = 292+/-58 min) correlated well (r = 0.94). Altman-Bland statistics showed close agreement between scintigraphy and breath test. No significant difference between male and female subjects was observed. CONCLUSION: The breath test using 13C-LU is a valid alternative to scintigraphy techniques for measuring OCTT.

Gastric emptying in formula-fed and breast-fed infants measured with the 13C-octanoic acid breath test.

BACKGROUND: The 13C-octanoic acid breath test, a noninvasive method for measuring gastric emptying, was used to compare the gastric-emptying rate of formula-fed and breast-fed infants. Octanoic acid, a medium-chain fatty acid marked with the stable isotope 13C is immediately absorbed in the duodenum. Because gastric emptying is the rate-limiting step for the absorption of medium-chain fatty acids, the fraction of 13C expired in the breath indicates the rate of gastric emptying. METHODS: Twenty-nine newborn infants (16 boys, 13 girls) were investigated, with parental consent. The infants had a mean gestational age at birth of 34.5 weeks (range, 27-41 weeks) and a birth weight of 2148 g (range, 960-4100 g). Their mean weight on the day of the test was 2496 g (range, 1998-4140 g), and their mean age was 23 days (range, 7-74 days). Each infant received a test meal after a maximum fasting period of 3 hours. Fourteen infants were fed formula milk (Nutrilon Premium, NV Nutricia, Zoetermeer, The Netherlands) with 13C-octanoic acid and 15 infants received expressed mother's milk mixed with 13C-octanoic acid. After obtaining two basal breath samples and the feeding, breath samples were collected using a nasal prong, every 5 minutes during the first half hour and every 15 minutes during the next 3.5 hours. Analysis of the expired 13C fraction in the breath samples was performed using isotope-ratio mass spectrometry, and the gastric emptying curve and gastric emptying parameters were determined. RESULTS: The mean half-emptying time determined by the 13C-octanoic acid breath test was 65 minutes (range, 27-98 minutes) for the formula fed infants and 47 minutes (range, 16-86 minutes) for the breast-fed infants. The difference between the half-emptying times is significant (t-test, p < 0.05). CONCLUSIONS: The results of the 13C-octanoic acid breath test indicated faster gastric emptying of human milk than formula. Our findings are in accordance with those in earlier studies, using the invasive-dilution technique; noninvasive and detailed ultrasonography, which is not easily used because it is operator dependent and the observation time is short; or cineesophago-gastroscintigraphy, which is less suitable for infants (because of the radiation involved). The 13C-octanoic acid breath test is a safe and noninvasive method for measuring gastric emptying in small infants and allows comparison of various feeding methods.

Effect of glutamine on the intestinal permeability changes induced by indomethacin in humans.

BACKGROUND: Long-term non-steroidal anti-inflammatory drug (NSAID) intake may induce increased intestinal permeability, eventually resulting in enteropathy. Because increased permeability might be related to cell damage resulting from energy depletion, it was hypothesized that glutamine--the major energy source of the intestinal mucosal cell--might prevent permeability changes. METHODS: The 6-h urinary excretion of 51Cr-EDTA after an oral load of 51Cr-EDTA was used in this study as a measure for intestinal permeability. Healthy volunteers underwent a series of permeability tests: (i) basal test; (ii) test following NSAID (indomethacin); (iii) test following NSAID in combination with glutamine and/or misoprostol. RESULTS: The NSAID induced increased permeability in all volunteers. Pre-treatment with glutamine (3x7 g daily, 1 week before NSAID-dosing) did not prevent the NSAID-induced increase in permeability. Multiple doses of glutamine close in time to NSAID-dosing resulted in significantly lower permeability compared to the NSAID without glutamine. Co-administration of misoprostol with the multiple-dose scheme of glutamine resulted in a further reduction in the NSAID-induced increase in permeability. CONCLUSIONS: Glutamine decreases the permeability changes caused by NSAID-dosing when it is administered close in time, and misoprostol has a synergistic effect.

Gastric emptying in hyperemesis gravidarum and non-dyspeptic pregnancy.

BACKGROUND: Emesis and hyperemesis are significant problems associated with early pregnancy. However, gastric emptying of solids has never been studied during early pregnancy in humans. AIM: To investigate gastric emptying of solids in patients recovering from hyperemesis gravidarum and in non-dyspeptic pregnant women and to compare these results with a group of healthy non-pregnant women. METHODS: Fourteen patients with hyperemesis gravidarum, 10 non-dyspeptic pregnant women and 36 non-pregnant women in the first half of the menstrual cycle underwent a gastric emptying study. Seven non-pregnant women repeated the test in the post-ovulatory period. RESULTS: Gastric emptying of solids was not significantly delayed in non-dyspeptic pregnant women compared with non-pregnant women. The emptying rate tended to be impaired in the post-ovulatory period of the menstrual cycle. Solid emptying was significantly accelerated in patients recovering from hyperemesis gravidarum, correlating well with thyroid function in the latter group. CONCLUSION: Pregnancy in humans is not associated with decreased solid gastric emptying. In subjects recovering from hyperemesis gravidarum, solid emptying is increased, correlating well with thyroid function abnormalities. Nausea and vomiting in hyperemesis are therefore probably not due to upper gastrointestinal disorders.

Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease.

BACKGROUND: Glutamine is a major fuel and an important nitrogen source for the small intestinal cell. It plays a key role in maintaining mucosal cell integrity and gut barrier function. Increased permeability may be a factor in the pathogenesis of Crohn's disease and may be an interesting parameter in the follow-up of the disease. Therefore, the aim of this study was to examine whether oral glutamine supplements are able to restore an increased intestinal permeability in patients with Crohn's disease. METHODS: The inclusion criteria for the study were Crohn's disease and a disturbed small intestinal permeability for 51Cr-EDTA. Of 38 patients screened, 18 had an increased permeability (6 hours urinary excretion >1.1% of label recovered in urine). Fourteen patients were included in the study and were randomized to receive either oral glutamine (7 g three times per day; n = 7) or placebo (7 g glycine three times per day; n = 7) in addition to their normal treatment during a 4-week period. The study was performed in a double-blind manner. RESULTS: Baseline permeability (mean +/- SD) was 2.32%+/-0.77% dose in the glutamine group and 2.29%+/-0.67% dose in the placebo group. Permeability did not change significantly after glutamine (3.26%+/-2.15% dose) or after placebo (2.27%+/-1.32% dose). There was no significant effect on plasma glutamine, plasma glutamate, plasma ammonium, Crohn's disease activity index, C-reactive protein, or nutritional status. CONCLUSIONS: Oral glutamine supplements, in the dose administered, do not seem to restore impaired permeability in patients with Crohn's disease.

Evidence for impaired assimilation and increased colonic fermentation of protein, related to gastric acid suppression therapy.

BACKGROUND: Although the role of gastric digestion (by acid-dependent pepsins) in overall protein assimilation has never thoroughly been studied, it is generally considered to be limited. Protein that escapes assimilation in the small intestine is intensely fermented by the colonic flora. Phenol and p-cresol are specific bacterial metabolites of tyrosine. AIM: To elucidate the role of gastric digestion of protein by evaluating the influence of acid suppression therapy on overall protein assimilation and fermentation. METHODS: Protein assimilation was studied in 16 healthy subjects under basal conditions and after omeprazole treatment using the combined 14C-octanoic acid/13C-egg white breath test. The degree of protein fermentation was estimated by measuring the urinary output of phenol and p-cresol in 41 healthy volunteers and in 17 patients treated for more than 1 month with omeprazole because of peptic disease. RESULTS: Protein assimilation was significantly impaired after omeprazole treatment. Gastric emptying, conversely, was not affected. The urinary output of phenol and p-cresol was increased in patients treated with omeprazole as compared to untreated controls. CONCLUSION: Gastric acid suppression therapy hampers protein assimilation and may promote protein malabsorption. Gastric digestion is likely to play a substantial role in overall protein assimilation.