- Email: [email protected]
There Are More Confounders in Omeprazole-Calcium Interaction
The American Journal of Medicine (2007) 120, e15
LETTER There Are More Confounders in OmeprazoleCalcium Interaction To the Editor: In July’s issue of the Journal, O’Connell et al1 revealed that calcium absorption from calcium carbonate during fasting is intragastric pH dependent and confirmed what had been reported 20 years ago by Recker.2 Because of widespread use of proton pump inhibitors (PPIs) and a common prescribing of the carbonate salt as a calcium supplement, calcium malabsorption may be a serious problem. Therefore, all confounders in PPI-calcium interaction should be taken into account. We are obliged to comment on several topics concerning O’Connell et al’s contribution. First, there is a large interindividual variability in intragastric pH in patients taking omeprazole.3 One important confounder is metabolizer type (poor, heterozygous or homozygous extensive) related to a polymorphism of the CYP2C19 gene responsible for PPI metabolism. Among extensive metabolizers, the most common in Caucasians, the homozygous ones had a median intragastric pH ⬎2 units lower and the percentage of time with intragastric pH ⬎4 about a half lower than heterozygous ones.4 From O’Connell et al’s 18 women, those 5 with a small change (⬍2%) in calcium absorption and the outlier with enhanced absorption on omeprazole were probably the homozygous extensive metabolizers. The second confounder is Helicobacter pylori status. The Helicobacter pylori-infected patients had a median intragastric pH in the corpus 1.5 units and in the antrum 2 units higher on omeprazole than subjects who were not infected.5 Second, calcium carbonate absorption from food is not intragastric pH dependent.2 However, the effect of longterm PPI therapy on calcium absorption has not been studied. From 29 patients with erosive esophagitis held in a 1-year remission on omeprazole, we followed-up for the next 2 years 16 patients (11 males) aged 59.8 ⫾ 3.3 (mean ⫾ SEM) years on 20 mg omeprazole, and 13 patients (8 males) aged 57.7 ⫾ 4.5 years on 30 mg cisapride, daily. Throughout the 3 years of follow-up, serum calcium did not differ between both well-matched groups, nor change compared with baseline (Figure).
0002-9343/$ -see front matter © 2007 Elsevier Inc. All rights reserved.
Figure Serum calcium levels in 29 esophagitis patients during a 1-year remission on omeprazole and the next 2 years follow-up on omeprazole (16 patients, black circles) or cisapride (13 patients, white circles). There were 4 drop-outs in each group until the end of follow-up. Data are shown as means and 95% confidence intervals. There were no significant differences versus baseline (Friedman’s ANOVA), nor between both groups (the MannWhitney test).
Third, if calcium supplement and PPI are required, patients should either take calcium carbonate with food, in divided doses, or should delay its intake from the morning dose of PPI until a nocturnal acid breakthrough is likely to happen to prevent calcium malabsorption. Tomasz Sikorski, MD, PhD Ewa Marcinowska-Suchowierska, MD, PhD Department of Family Medicine and Internal Diseases Medical Center for Postgraduate Education Warsaw, Poland
doi:10.1016/j.amjmed.2006.02.020
References 1. O’Connell MB, Madden DM, Murray AM, et al. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med. 2005;118:778-781. 2. Recker RR. Calcium absorption and achlorhydria. N Engl J Med. 1985;313:70-73. 3. Katz PO. Ambulatory intragastric pH monitoring: clinical laboratory to clinical practice. Rev Gastroenterol Dis. 2003;3(suppl 4):S3-S9. 4. Sagar M, Tybring G, Dahl ML, et al. Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism. Gastroenterology. 2000;119:670-676. 5. Verdú EF, Armstrong D, Fraser R, et al. Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole. Gut. 1995; 36:539-543.
LETTER There Are More Confounders in OmeprazoleCalcium Interaction To the Editor: In July’s issue of the Journal, O’Connell et al1 revealed that calcium absorption from calcium carbonate during fasting is intragastric pH dependent and confirmed what had been reported 20 years ago by Recker.2 Because of widespread use of proton pump inhibitors (PPIs) and a common prescribing of the carbonate salt as a calcium supplement, calcium malabsorption may be a serious problem. Therefore, all confounders in PPI-calcium interaction should be taken into account. We are obliged to comment on several topics concerning O’Connell et al’s contribution. First, there is a large interindividual variability in intragastric pH in patients taking omeprazole.3 One important confounder is metabolizer type (poor, heterozygous or homozygous extensive) related to a polymorphism of the CYP2C19 gene responsible for PPI metabolism. Among extensive metabolizers, the most common in Caucasians, the homozygous ones had a median intragastric pH ⬎2 units lower and the percentage of time with intragastric pH ⬎4 about a half lower than heterozygous ones.4 From O’Connell et al’s 18 women, those 5 with a small change (⬍2%) in calcium absorption and the outlier with enhanced absorption on omeprazole were probably the homozygous extensive metabolizers. The second confounder is Helicobacter pylori status. The Helicobacter pylori-infected patients had a median intragastric pH in the corpus 1.5 units and in the antrum 2 units higher on omeprazole than subjects who were not infected.5 Second, calcium carbonate absorption from food is not intragastric pH dependent.2 However, the effect of longterm PPI therapy on calcium absorption has not been studied. From 29 patients with erosive esophagitis held in a 1-year remission on omeprazole, we followed-up for the next 2 years 16 patients (11 males) aged 59.8 ⫾ 3.3 (mean ⫾ SEM) years on 20 mg omeprazole, and 13 patients (8 males) aged 57.7 ⫾ 4.5 years on 30 mg cisapride, daily. Throughout the 3 years of follow-up, serum calcium did not differ between both well-matched groups, nor change compared with baseline (Figure).
0002-9343/$ -see front matter © 2007 Elsevier Inc. All rights reserved.
Figure Serum calcium levels in 29 esophagitis patients during a 1-year remission on omeprazole and the next 2 years follow-up on omeprazole (16 patients, black circles) or cisapride (13 patients, white circles). There were 4 drop-outs in each group until the end of follow-up. Data are shown as means and 95% confidence intervals. There were no significant differences versus baseline (Friedman’s ANOVA), nor between both groups (the MannWhitney test).
Third, if calcium supplement and PPI are required, patients should either take calcium carbonate with food, in divided doses, or should delay its intake from the morning dose of PPI until a nocturnal acid breakthrough is likely to happen to prevent calcium malabsorption. Tomasz Sikorski, MD, PhD Ewa Marcinowska-Suchowierska, MD, PhD Department of Family Medicine and Internal Diseases Medical Center for Postgraduate Education Warsaw, Poland
doi:10.1016/j.amjmed.2006.02.020
References 1. O’Connell MB, Madden DM, Murray AM, et al. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med. 2005;118:778-781. 2. Recker RR. Calcium absorption and achlorhydria. N Engl J Med. 1985;313:70-73. 3. Katz PO. Ambulatory intragastric pH monitoring: clinical laboratory to clinical practice. Rev Gastroenterol Dis. 2003;3(suppl 4):S3-S9. 4. Sagar M, Tybring G, Dahl ML, et al. Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism. Gastroenterology. 2000;119:670-676. 5. Verdú EF, Armstrong D, Fraser R, et al. Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole. Gut. 1995; 36:539-543.