Interaction between vitamin K nutriture and bacterial overgrowth in hypochlorhydria induced by omeprazole.

Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P < 0.05) and were not significantly different in the period when the diet was combined with omeprazole treatment (P > 0.05). The mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.

Gastric emptying and first-pass metabolism of ethanol in elderly subjects with and without atrophic gastritis.

BACKGROUND: Oral ethanol intake results in lower blood ethanol concentrations than intravenous administration of the same dose of ethanol. This first-pass metabolism is thought to be due to gastric metabolism of ethanol via alcohol dehydrogenase and also to hepatic first-pass metabolism. METHODS: Since a loss of gastric mucosa may decrease first-pass metabolism of ethanol, this metabolism was studied in 10 elderly subjects (6 women and 4 men) with atrophic gastritis and bacterial overgrowth and in 17 control subjects with normal gastric secretory function. Atrophic gastritis was verified by means of the serum pepsinogen I to pepsinogen II ratio and the hypochlorhydria occurring after pentagastrin stimulation. Bacterial overgrowth was assessed by bacteria. In addition, gastric emptying rates of ethanol solution with technetium-99m sulfur colloid were calculated from scintigraphic images. Furthermore, gastric biopsy specimens were taken from 12 female patients with atrophic gastritis and from 12 controls for determination of alcohol dehydrogenase activity. RESULTS: Neither gender (female versus male, 28 +/- 5% versus 42 +/- 5%), atrophic gastritis (normal versus atrophic gastritis, 35 +/- 4% versus 32 +/- 6%), nor tetracycline treatment in atrophic gastritis subjects (before versus after, 32 +/- 6% versus 41 +/- 5%) had a statistically significant effect on the first-pass metabolism of ethanol in the elderly. Gastric alcohol dehydrogenase activity was significantly lower in atrophic gastritis subjects than in controls (p < 0.01). A significant correlation was found between the first-pass metabolism of ethanol in healthy controls and gastric half-emptying time (p = 0.032). CONCLUSIONS: We conclude from these data that the rate of gastric emptying modulates first-pass metabolism of ethanol in elderly individuals.

Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans.

OBJECTIVE: Low gastric pH is generally believed to be an important factor in intestinal mineral absorption. Thus, hypochlorhydria could be an important risk factor for mineral malabsorption and the development of marginal mineral status. We studied whether the hypochlorhydria associated with treatment with the anti-ulcer medication omeprazole, a potent gastric proton pump inhibition, would affect intestinal calcium, phosphorus, magnesium, or zinc absorption from food. METHODS: Thirteen normal, healthy adults were assigned to either a control group (n = 5) receiving no drug treatment or an omeprazole treatment group (n = 8) to produce increased gastric pH. Omeprazole treatment of normal volunteers resulted in a significant change in postprandial gastric pH (pH 6.4 +/- 0.3 vs. 3.6 +/- 0.5 in control subjects, p < 0.01) and baseline fasting pH (pH 5.8 +/- 0.5 vs. pH 1.8 +/- 0.3 in controls, p < 0.01) after an overnight fast. Net mineral absorption from a standard test meal was measured using a whole gut lavage technique. Mineral absorption was measured twice in each subject, once with 120 mL of 0.1 mol/liter hydrochloric acid and a second time with 120 mL of distilled water alone. RESULTS: We found that despite marked changes in gastric pH due to drug treatment or administration of exogenous HCl, no change in the intestinal absorption of calcium, phosphorus, magnesium or zinc from a standard test meal was evident. CONCLUSIONS: These findings suggest that changing the gastric pH alone does not modify the net intestinal absorption of several minerals from food. Therefore, it is unlikely that moderate hypochlorhydria resulting from short-term omeprazole treatment substantially increases the risk for developing calcium, phosphorus, magnesium, or zinc deficiencies due to mineral malabsorption.

Bacterial overgrowth without clinical malabsorption in elderly hypochlorhydric subjects.

BACKGROUND/AIMS: Bacterial overgrowth of the small intestine commonly occurs in association with hypochlorhydria caused by atrophic gastritis or during treatment with omeprazole. The purpose of this study was to determine the clinical significance of bacterial overgrowth on small intestinal absorption and permeability and to evaluate the reliability of noninvasive breath tests to detect bacterial overgrowth in subjects with hypochlorhydria. METHODS: Seventeen healthy, elderly subjects with atrophic gastritis or omeprazole treatment (40 mg/day) and documented bacterial overgrowth were studied. RESULTS: There was no evidence of fat malabsorption (72-hour fecal fat) or clinically significant carbohydrate malabsorption (25 g D-xylose and fecal pH) in any subject. The ratio of lactulose to mannitol excreted was normal in both atrophic gastritis and omeprazole-treated groups. Three subjects in each group had abnormally high alpha 1-antitrypsin clearances. Lactulose (10 g) and glucose (80 g) hydrogen breath tests were only abnormal in 1 out of 17 subjects, whereas the 1 g [14C]D-xylose test was abnormal in 6 out of 17 subjects. CONCLUSIONS: Bacterial overgrowth caused by atrophic gastritis or omeprazole treatment is typically not associated with clinically significant fat or carbohydrate malabsorption. Noninvasive breath tests for bacterial overgrowth are not reliable in subjects with hypochlorhydria.