Effects of omeprazole consumption on serum levels of trace elements

ARTICLE IN PRESS
Contents lists available at Journal of Trace Elements in Medicine and Biology Effects of omeprazole consumption on serum levels of trace elements Hamidreza Joshaghani , Taghi Amiriani , Gholamreza Vaghari , Sima Besharat , Aliasghar Molana , Mohammadtaghi Badeleh , Gholamreza Roshandel a Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran b Biochemistry and Metabolic Disease Research Center, Golestan University of Medical Sciences„ Gorgan, Iran c Golestan University of Medical Sciences, Gorgan, Iran Project: Omeprazole is one of the most frequently prescribed drugs in patients with gastroesophageal Received 21 December 2010 reflux disease (GERD). It increases the gastric pH and this in turn may change the intestinal absorption of Accepted 7 February 2012 trace elements. This study was conducted to assess the effects of omeprazole consumption on the serum level of trace elements.
Procedures: The studied subjects were selected from the list of patients referred to the gastroenterology department of 5 Azar hospital in Golestan province of Iran for whom omeprazole was prescribed by a gastroenterologist. Blood samples were obtained before (phase I) and after an eight-week period (phase Gastroesophageal reflux disease II) of omeprazole consumption. Serum levels of trace elements were assessed by the photometric method.
Results: Sixty seven patients were recruited of whom, 35.82% were males. There was no significant dif- ference in serum levels of Fe, P, Ca and Cu between phases I and II. Serum concentration of Zn was significantly lower in phase II than I (P = 0.02). The proportion of male patients with low Zn levels was significantly higher in phase II (50%) than I (16.7%) (P = 0.01). We found no significant difference in the proportion of female patients with low Zn levels between phase I (37.2%) and phase II (27.9%).
Conclusions: We found no significant reduction in serum levels of Fe, P, Ca and Cu in phase II. However, our results showed that serum level of Zn was significantly lower after omeprazole consumption in males.
So, nutritional supplement of Zn should be considered in male patients treated with omeprazole.
2012 Elsevier GmbH. All rights reserved.
particles such as trace elements. Absorption of trace elements often takes place in acidic media of stomach and proximal part of small Gastroesophageal reflux disease (GERD) is a kind of disease intestine. Some elements such as calcium (Ca), phosphorous (P) occurred when distal esophageal muscle does not close the sphinc- and iron (Fe) are soluble in acidic medium and insoluble in the ter completely. This change results in abnormal reflux of gastric alkaline environment gastric PH interferes with the acid into the esophagus. The typical symptom of GERD is heart- absorption of the above mentioned elements addition to indi- burn It is estimated that GERD symptoms occur in up to rect effect of omeprazole on the absorption of trace elements, some 40% of population is one of the most frequently studies reported that omeprazole may directly block the absorption prescribed drugs in GERD patients. However, sometimes patients of Ca and other minerals take it inappropriately and without physician's prescription Trace elements play important roles in a number of body func- Omeprazole is available in the form of 20 mg capsule can tions. Ca is the most abundant mineral in the body and a large relieve sign and symptoms of GERD. This drug is considered as an amount of it is deposited in bone and teeth. Reduction of Ca level in anti-gastric acid agent and its mechanism is to inhibit proton pump the body may cause some abnormalities such as osteoporosis and in the gastric mucosa and consequently, to reduce gastric acidity.
osteomalacia and rickets. The absorption of intestinal P follows the Omeprazole inhibits proton pumps by blocking the production of absorption of Ca. So, impairing the absorption of Ca due to omepra- gastric hydrochloric acid and changes the gastric pH to alkaline zole consumption may in turn lead to changes in the absorption of range. Gastric acidity plays an important role in absorption of food P (Zn) deficiency may results in growth delay, infertility in males, immune system dysfunction and cognitive impairment (Cu) is a co-factor for at least 30 enzymes. It is directly absorbed through gastrointestinal (GI) tract Over-use Corresponding author at: Number 77, Qabooseieh Passage, Valiasr Street, Gorgan of omeprazole may cause trace elements deficiency and this may 49166-53588, Iran. Tel.: +98 171 2340835; fax: +98 171 2369210.
E-mail address: (G. Roshandel).
lead to abnormalities in some of important body functions.
0946-672X/$ – see front matter 2012 Elsevier GmbH. All rights reserved.
Please cite this article in press as: Joshaghani H, et al. Effects of omeprazole consumption on serum levels of trace elements. J Trace Elem Med Biol (2012), ARTICLE IN PRESS
H. Joshaghani et al. / Journal of Trace Elements in Medicine and Biology xxx (2012) xxx–xxx Golestan province, located in northeast of Iran, is known as a high-risk area for upper GI (UGI) cancers. Symptoms of UGI problems, including GERD may wrongly be considered as mani- festations of a malignant condition. These patients are frequently visited by various physicians. This in turn may result in inappro- priate use and over-use of medicines such as omeprazole in this region. Therefore, we conducted this study to determine the effects of omeprazole consumption on the serum levels of Cu, Zn, Ca, P, Fe and erythrocyte indices of patients in Golestan province of Materials and methods
The studied subjects were selected from the list of patients referred to the department of gastroenterology in 5 Azar hospital of Golestan province of Iran for whom omeprazole was prescribed by a gastroenterologist. Patients who did not take the drug regu- larly or consumed supplementary drugs containing Ca, P, Fe, Cu and Zn were excluded. Patients were referred to the biochemi- cal laboratory of the Golestan University of Medical Sciences for blood sampling in two phases. The first sampling (phase I) was done before starting omeprazole therapy and the second sam- ple (phase II) was collected after finishing an eight-week period of omeprazole consumption. Three ml of blood was taken from each of the participants. Complete Blood Count (CBC) was per- formed immediately after sampling by cell counter Sysmex KX-21, Japan. Then, serum was separated and stored at −80 ◦C until used.
The trace elements were measured by Mindray BS-200 autoana- lyzer, China. Ca, P and Fe were assayed by Parsazmoon kit (Iran).
Cu and Zn were assessed by Greiner kit (Germany) and Elithec kit (France), respectively. To reduce the bias of the colorimetric and chemical methods, all tests were performed twice, and the mean values were considered for analysis. Paired t-test, Student's t-test, Mann–Whitney U test and Chi-square test were used for data analysis. P-values of less than 0.05 were considered as sig- Sixty seven 20–50 years-old patients were recruited in the study. Twenty four (35.82%) of the participants were male. Serum concentration of Zn was significantly lower in phase II than phase I (P = 0.02). There was no significant difference in serum levels of Fe, P, Ca and Cu between phases I and II. the mean and standard deviation of trace elements before and after omepra- zole consumption. The results of erythrocyte indices are shown in Serum levels of Ca and P in all male patients were within ref- erence interval before omeprazole consumption. After omeprazole consumption, the levels of Ca and P in 16.7% of male patients were lower than reference interval. The proportion of male patients with low Cu levels was the same in phases I and II. The proportion of male patients with low Zn levels was significantly higher in phase II (50%) than phase I (16.7%) (P = 0.01). After omeprazole consump- tion, serum concentration of all variables except Fe and Cu were lower than reference interval in 16.7% of males.
Serum levels of Fe, Cu and Ca were within reference interval in all females both in phases I and II. All female patients had normal levels of P before omeprazole consumption, but serum level of P in 9.3% of females was lower than reference interval in phase II. We found no significant difference in the proportion of female patients with low Zn levels between phase I (37.2%) and phase II (27.9%) Please cite this article in press as: Joshaghani H, et al. Effects of omeprazole consumption on serum levels of trace elements. J Trace Elem Med Biol (2012), doi: ARTICLE IN PRESS
H. Joshaghani et al. / Journal of Trace Elements in Medicine and Biology xxx (2012) xxx–xxx Discussion and conclusion
The aim of this study was to assess the effects of omeprazole consumption on serum levels of trace elements. There was a sig- nificant difference in serum levels of Zn and Cu between males and females before omeprazole consumption. This may be due to differences in nutritional status or physiological state of the dis- ease between males and females. We found that Zn had more been affected by omeprazole consumption than other variables.
Our findings showed a significant reduction in serum Zn levels after omeprazole consumption in males. In the other hand, the proportion of male patients with low Zn level was 16.7% and 50% before and after omeprazole consumption, respectively. Hiroshi et al. reported a significant lower serum Zn level in omeprazole treated rats than controls result of a study by Ozutemiz et al. was in line with ours and suggested that omeprazole reduces intestinal Zn absorption by decreasing gastric pH results of Alastair's study suggested that low gastric pH may not be necessary for intestinal absorption of Zn Our results showed no significant difference in serum levels of Ca, Fe, Cu and P between phases I and II. Mizunashi et al.
reported that elimination of Ca through urine decreased after using omeprazole the study of Graziani et al., serum level of Ca was decreased significantly after omeprazole consumption.
They reported no significant difference in the placebo group. They also found no significant relationship between serum P level and omeprazole or placebo consumption Edemilson Cardoso da Conceic et al. reported a significant increase in serum transferrin and a decrease in hepatic Iron after four weeks as well as a reduction in Hb level after six weeks of omeprazole consumption in rats. Cases received Iron supplement (Fe or Fe3+) in addition with omepra- zole showed no difference in Hb and serum transferrin compare to Serfaty-Lacrosniere et al. suggested that omeprazole consump- tion led to a significant increase in gastric pH in omeprazole treated patients than controls. However, they did not find a significant dif- ference in intestinal absorption of Ca, P, Mg and Zn between the two groups. So, they concluded that change in gastric pH may not be the only factor affecting the intestinal absorption of trace elements of the results of our study considering Ca and P were in line with Serfaty-Lacrosniere's one. Although, chemical method is not the gold standard for assessing these trace elements, but it is routinely used in medical laboratories and physicians accept the results of this method for clinical judgment. Therefore, the results of the present research are near to the results reported in medi- cal laboratories. Serum level of trace elements was assessed by the same method both in phases I and II. So, method variation was not an important concern for interpretation of the results in this study.
In conclusion, we found no significant reduction in serum levels of Fe, P, Ca and Cu in phase II compare to phase I. However, our results showed that serum level of Zn was significantly lower after omeprazole consumption in males. So, nutritional supplements of Zn should be considered in male patients treated by omeprazole.
This project was approved and supported by Golestan University of Medical Sciences.
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