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Effects of Omeprazole on Vitamin and Mineral Absorption and Metabolism

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Effects of Omeprazole on Vitamin and Mineral Absorption and Metabolism

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Objective To examine the literature surrounding the effects of omeprazole on oral iron absorption and discuss the long-term use of omeprazole and its effect on vitamins C and B 12 , calcium, and magnesium absorption. Data Sources The PubMed and MEDLINE databases were searched for reports published in English between January 1968 and August 2012, using the terms absorption, ascorbic acid, proton pump inhibitor, omeprazole, magnesium, calcium, ferrous sulfate, iron, and drug interactions. Study Selection and Data Extraction Studies and reports published in English were selected for review. In some cases, reference citations from selected review articles were evaluated as well. Data Synthesis Several micronutrients require an acidic environment for optimal absorption. Iron, vitamin C, and vitamin B 12 absorption are dependent on the intestine's acidic environment. Several studies and case reports describe associations of omeprazole with altered calcium, magnesium, and vitamin B 12 absorption. To date, there have been no prospective trials evaluating the effect of proton pump inhibitors (PPIs) on iron absorption. Conclusions Existing data support the conclusion that the acid-suppressing effect of omeprazole can have important clinical implications for vitamin and mineral therapy. Clinicians should be cognizant of this issue in practice. Further studies exploring the relationship of PPIs and iron deficiency are warranted, especially in high-risk populations such as the elderly.

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... However, several researchers have demonstrated that PPI treatment is not without side effects, most likely because the reduction of gastric pH can modify digestion and the absorption of nutrients throughout the digestive tract, changing the concentration of some biomarkers in the blood [5][6][7][8][9]. ...
... However, several researchers have demonstrated that PPI treatment is not without side effects, most likely because the reduction of gastric pH can modify digestion and the absorption of nutrients throughout the digestive tract, changing the concentration of some biomarkers in the blood [5][6][7][8][9]. ...
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Iron deficiency is widely observed worldwide, yet, paradoxically, iron is the most plentiful heavy metal in the earth's crust. Although absorption of iron from the gastrointestinal tract is strictly controlled, excretion is limited to iron lost from exfoliation of skin and gastrointestinal cells, customary and abnormal blood loss, and menses. Individuals highly vulnerable to iron deficiency have high iron needs, as during growth or pregnancy; high iron loss, as during marked hemorrhage or excessive and/or frequent menstrual losses; or diets with low iron content or bioavailability. Food iron is classified as heme or nonheme. Approximately half of the iron in meat, fish, and poultry is heme iron. Depending on an individual's iron stores, 15% to 35% of heme iron is absorbed. Food contains more nonheme iron and, thus, it makes the larger contribution to the body's iron pool despite its lower absorption rate of 2% to 20%. Absorption of nonheme iron is markedly influenced by the levels of iron stores and by concomitantly consumed dietary components. Enhancing factors, such as ascorbic acid and meat/fish/poultry, may increase nonheme iron bioavailability fourfold.
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Article
The first case of cobalamin deficiency with megaloblastic anaemia in a patient under long-term omeprazole therapy is presented. This patient received omeprazole at a daily dose of 40-60 mg for 4 years as treatment for a gastro-oesophagal reflux complicated by peptic oesophagitis. Seric vitamin B12 was dramatically decreased at 80 pmol L-1. The Schilling test was normal (13%) with crystalline [57Co] cobalamin and it was at 0% with [57Co] cobalamin-labelled trout meat. All other assimilation tests were normal except an expiratory hydrogen breath test performed with lactulose. The haematological status was restored after intramuscular treatment with cobalamin. In conclusion, prolonged omeprazole therapy can be responsible for a cobalamin deficiency due to protein-bound cobalamin malabsorption.
Article
Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores. To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger-Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs. One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/ transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters. Eighty-nine patients were taking omeprazole, nine patients were taking histamine H2-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7-12.5 years) and total duration of any treatment was 10.1 years (range 0.7-21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency. Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary.
Article
The S-mephenytoin hydroxylase is a polymorphic cytochrome P450 (CYP) enzyme, identified as CYP2C19, which catalyses the metabolism of omeprazole and some other drugs. To determine whether long-term treatment with omeprazole affects serum vitamin B12 levels, and if so to what extent it depends on CYP2C19 activity. Serum vitamin B12 levels (pmol/L) were assessed in 179 patients. Genotyping for wild-type (wt) and mutated (mut) CYP2C19 alleles was performed by allele-specific PCR amplification. One-hundred and eleven of the patients received one dose of 20 mg omeprazole. No difference in B12 levels were found between heterozygous (wt/mut) (n = 23) and homozygous (wt/wt) (n = 85) patients (mean +/- s.d., 350 +/- 82 vs. 315 +/- 87 pmol/L, respectively). Three patients were mut/mut, with serum vitamin B12 levels of 303 +/- 50 pmol/L. In the 68 patients on long-term (>1 year) therapy with 20 mg omeprazole daily, serum vitamin B12 levels were lower in the heterozygous (wt/mut) (n = 19) compared to homozygous wt/wt (n = 49) (246 +/- 71 vs. 305 +/- 98 pmol/L, P = 0. 01, respectively). In one patient (mut/mut) who was studied both after a single dose and after long-term (15 months) treatment with omeprazole, serum vitamin B12 decreased from 360 to 178 pmol/L. In the wt/mut, but not in the wt/wt group, serum vitamin B12 levels were significantly lower in patients on long-term therapy compared with those receiving one dose (246 +/- 71 vs. 350 +/- 82 pmol/L, P < 0.0001, respectively). CYP2C19 polymorphism significantly affected serum vitamin B12 levels in patients on long-term therapy with omeprazole. In the future, genotyping of CYP2C19 may be useful for patients in need of long-term treatment with omeprazole or other proton pump inhibitors.
Article
Since their introduction into clinical practice in the 1980s, proton pump inhibitors (PPIs) have proved to be of enormous value in the management of acid peptic disorders. They have become the treatment of choice for most, if not all, acid-related gastrointestinal disorders, including gastroesophageal reflux disease, peptic ulcer, and Zollinger-Ellison syndrome. With approval of an intravenous formulation, the benefits of PPIs are extended to critically ill patients for whom oral drug administration is often unsuitable. Five PPIs are approved for clinical use in the United States. Although they share a common core structure and mechanism of action, it is important to understand the general pharmacology of these agents and how they differ from histamine2-receptor antagonists in order to optimize PPI therapy.
Article
Acid-suppressant drugs are commonly prescribed for elderly patients, a population in which vitamin B(12) deficiency is a common disorder. The purpose of this study was to examine the possible association between use of prescription histamine H-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) and vitamin B(12) deficiency in older adults. This was a case-control study in a University-based geriatric primary care setting. Among patients aged 65 years or older with documented serum vitamin B(12) studies between 1990 and 1997, 53 vitamin B(12)-deficient cases were compared with 212 controls for past or current use of prescription H2RA/PPI according to information in subjects' medical records. Controlling for age, gender, multivitamin use, and Helicobacter pylori infection, chronic (#10878;12 months) current use of H2RA/PPI was associated with a significantly increased risk of vitamin B(12) deficiency (OR 4.45; 95% CI 1.47-13.34). No association was found between past or short-term current use of H2RA/PPI and vitamin B(12) deficiency. These findings support an association between chronic use of H2RA/PPI by older adults and development of vitamin B(12) deficiency. Additional studies are needed to confirm these findings.
Article
Hypochlorhydric states such as atrophic gastritis and partial gastrectomy have long been known to cause iron deficiency anemia. However, studies to date have failed to show a similar association with omeprazole, a proton pump inhibitor that also produces achlorhydria. These studies, however, have primarily involved nonanemic, iron-replete individuals. The effect of the drug has not been studied in patients with established iron deficiency, and to our knowledge the patients presented here are the first of their kind to be reported. Our observations support the probability that the profound hypochlorhydria induced by omeprazole may indeed impair the optimal absorption of orally administered iron in iron-deficient individuals, precluding them from obtaining therapeutically adequate amounts to establish the positive balance necessary for the resolution of anemia and the replenishment of stores. The possible explanations for this phenomenon are also discussed.
Article
Objectives/hypothesis: A major trend in gastroesophageal reflux disease (GERD) is an observed increased prevalence of the problem, with an associated burden on health care resources. There are relatively few objective reports of increasing prevalence of this disease, and there are no epidemiologic reports that discuss changing practice strategies in managing the disease. The clinical problem is of critical importance to practicing otolaryngologists, who manage the impact of GERD on diseases affecting the ear, nose, and throat. The hypothesis of this thesis is that 1) GERD is an increasing problem affecting outpatient office visits over time, and 2) the disease is increasingly managed with prescription pharmacotherapy. Study design: Retrospective national medical database review using the National Ambulatory Medical Care Survey. Methods: Twelve years of data (1990-2001) were examined with visits weighted to provide U.S. estimates of care. Average annual frequencies and visit rates were calculated for total visits and by age, sex, race, and physician specialty. Selected issues in GERD treatment were also examined, including prescriptions and physician/patient counseling regarding stress management, tobacco abuse, and diet modification. Trends were reported based on changes in care across three time periods to satisfy statistical significance: 1990 to 1993, 1994 to 1997, and 1998 to 2001. Results: Between 1990 and 1993 and 1998 and 2001, there was a significant increase in U.S. ambulatory care visits for GERD, from a rate of 1.7 per 100 to 4.7 per 100. There were no significant changes in race, although there was a small trend toward increased GERD visits in the age group over 44 years old and in the male sex. Office visits to otolaryngologists increased from 89,000 to 421,000 between the time periods of 1990 to 1993 and 1998 to 2001. This also represented a percent increase in office encounters by otolaryngologists compared with visits by all specialties from 2.9% to 4.4%. Over the three time periods, there was a fall in prescriptions for histamine (H2) blockers from 58.1% to 20.7% of total prescriptions. Over the same three time periods, prescriptions of proton pump inhibitors increased from 13.2% to 64.6%. Physician recommendations for over the counter medications fell from 18.8% to 6.6%. Average annual counseling during ambulatory care visits for GERD was assessed for the period from 1998 to 2001 as follows: diet counseling was provided at 27.2% of encounters, tobacco cessation counseling was provided at 3.9%, and stress management was discussed at 3.9%. Conclusions: During the 1990s, there was a substantial increase in the use of ambulatory care services for GERD. Although much of this increase was among the primary care community, otolaryngologists appeared to have an increasingly prominent role in the management of this disease. There have also been dramatic changes in physician prescribing patterns for GERD, with the emergence of the predominant role of proton pump inhibitors. However, the use of physician counseling for lifestyle modification of factors known to affect GERD remains very low. The increasing impact of GERD on physician practice emphasizes the importance of both physician and patient education in the delivery of health care related to this disease.
Article
This study documents the number of ambulatory visits associated with gastroesophageal reflux disease (GERD) in the United States. Sample data from nearly 80,000 patients captured by the National Ambulatory Medical Care Survey (NAMCS; 1998-2001) were analyzed. Basic demographics of patients with GERD and factors associated with each visit were assessed. Approximately 38.53 million of 2.653 billion adult outpatient visits made in the United States during the study period were GERD-related. GERD-related visits increased by 46.5% from 1998 to 2001. Most GERD-related visits were by women (54.7%) with an average age of 56.0 years, compared with patients without GERD, who were even more likely to be women (62.2%) and younger (52.6 years). Patients with GERD were more likely to have multiple reasons (50.5%) and multiple diagnoses (79.3%) per medical visit versus non-GERD patients (37.6% and 48.4%, respectively). Utilization of data from the NAMCS reveals that GERD-related visits increased annually during the study period. Patients with GERD are more likely to see a physician if they have concomitant medical conditions, making GERD a condition that is very likely untreated in a high percentage of individuals.
Article
Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.
Article
Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid accumulation in the parietal cell through protonation, followed by activation mediated by a second protonation at the active secretory canaliculus of the parietal cell. The relative ease with which these steps occur with different proton pump inhibitors underlies differences in their rates of activation, which in turn influence the location of covalent binding and the stability of inhibition. Slow activation is associated with binding to a cysteine residue involved in proton transport that is located deep in the membrane. However, this is inaccessible to the endogenous reducing agents responsible for restoring H+/K+-ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel proton pump inhibitor which has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors, are activated more slowly than other proton pump inhibitors but their inhibition is resistant to reversal. In addition, tenatoprazole has a greatly extended plasma half-life in comparison with all other proton pump inhibitors. The chemical and pharmacological characteristics of tenatoprazole give it theoretical advantages over benzimidazole-based proton pump inhibitors that should translate into improved acid control, particularly during the night.
Article
To the Editor: We report two cases of hypomagnesemic hypoparathyroidism associated with the use of proton-pump inhibitors, in which patients presented with carpopedal spasm in association with severe hypomagnesemia and hypocalcemia without an appropriate increase in the level of parathyroid hormone. Patient 1 was a 51-year-old premenopausal woman who had been taking omeprazole for more than a year (at a dose of 20 mg twice daily) and who presented with carpopedal and truncal spasm. She began receiving 2.4 g of elemental calcium per day and, later, high-dose magnesium (Figure 1A). Fourteen months later, omeprazole was discontinued, and ranitidine initiated. The . . .
Article
To examine the relationship between serum vitamin B12 levels in older adults on histamine(2) receptor antagonists (H2 blockers) or proton-pump inhibitors (PPI) over 6 years. Participants: A cross-sectional sample of 659 adults, 60 to 102 years, from long-term care facilities and community ambulatory care (C) in the Bronx. Patient demographics, serum B12 levels, use and duration of use of H2 blockers, PPIs, antacids, multivitamin/minerals, liquid dietary supplements, oral vitamin B12 supplementation, oral or intramuscular B12 therapy, and recent lab chemistries. Acid-lowering agents (ALA) were used by 54% (PPIs by 26% and H2 blockers by 28%), duration averaged 18.2 +/- 16.0 (SD) months. NH and C subjects had similar ages (P = .9971), gender distributions (P = .625), durations of ALA use (P = .1227), and rates of PPI use (P = .130); NH subjects used more H2 blockers (P < .0005) and had less low B12 status (P = .037). H2 blocker use did not influence serum B12 status (P = .1036) while PPI use was associated with diminished serum B12 levels (P < .00005). Concomitant oral B12 supplementation slowed but did not prevent the decline in B12 status during prolonged PPI use (P = .0125). B12 status declines during prolonged PPI use in older adults, but not with prolonged H2 blocker use; supplementation with RDA amounts of B12 do not prevent this decline. This report reinforces that B12 deficiency is common in the elderly and suggests that it appears prudent to monitor periodically B12 status while on prolonged PPI use, to enable correction before complications ensue.
Article
Recent identification and characterization of novel Mg transporters have clarified our understanding of intestinal magnesium absorption. The predominant Mg transporters include TRPM6 and TRPM7, members of the transient receptor potential melastatin family of cation channels. Mutations of TRPM6 result in a primary disorder termed hypomagnesemia with secondary hypocalcemia. Both TRPM6 and TRPM7 channels possess an atypical alpha-kinase domain. Recent studies have shown that TRPM7 channel activity is regulated by intracellular Mg and magnesium-nucleotides and modulated via this phosphotransferase kinase. TRPM6 channel function and intestinal magnesium absorption is altered by a variety of hormones and factors. Although it is apparent that TRPM6 and TRPM7 form heteromeric ion channels, controversy surrounds the nature of this interaction. Some studies show that TRPM6 may function on its own whereas other research concludes that TRPM7 is required for effective trafficking of TRPM6 to the plasma membrane. Finally, a number of other Mg transporters have been identified in intestinal epithelial cells but the role of these proteins is unclear. The recent developments in intestinal magnesium absorption and cellular magnesium homeostasis provide a basis for understanding magnesium deficiency disorders and provide a platform for future investigations.
Article
The most severe consequence of iron depletion is iron deficiency anemia (IDA), and it is still considered the most common nutrition deficiency worldwide. Although the etiology of IDA is multifaceted, it generally results when the iron demands by the body are not met by iron absorption, regardless of the reason. Individuals with IDA have inadequate intake, impaired absorption or transport, physiologic losses associated with chronological or reproductive age, or chronic blood loss secondary to disease. In adults, IDA can result in a wide variety of adverse outcomes including diminished work or exercise capacity, impaired thermoregulation, immune dysfunction, GI disturbances, and neurocognitive impairment. In addition, IDA concomitant with chronic kidney disease or congestive heart failure can worsen the outcome of both conditions. In this review, the prevalence of IDA related to confounding medical conditions will be described along with its diverse etiologies. Distinguishing IDA from anemia of chronic disease using hematologic measures is reviewed as well. In addition, current diagnostic strategies that are inclusive of clinical presentation, biochemical tests, and differential diagnosis will be outlined, followed by a discussion of treatment modalities and future research recommendations.