daw
02-25-2004, 01:42 AM
Effect of PPI Therapy on Serum Gastrin, B12, and Iron Levels
Question:
What is the effect of proton-pump inhibitors (PPIs) on serum gastrin levels?...on vitamin B12 levels?...on serum iron levels?
Alan K. Hendra, MD
Response from M. Brian Fennerty, MD
Professor of Medicine, Section Chief of Gastroenterology, Oregon Health Sciences University, Portland, Oregon
The basis for these questions is the fact that levels of all 3 of these substances (hormones, vitamins, and elements) are in some way dependent on or related to gastric acid secretion. As such, any agent that affects gastric acid secretion may affect these specific substances, and because PPIs are potent antisecretory agents, they should in turn affect them to a greater degree.
Gastrin is a potent acid secretagogue that is released from "G" cells in the antrum of the stomach and the duodenum in response to a meal. The feedback inhibition for gastrin is acid present in the lumen of the stomach and small intestine. The use of any agent that inhibits gastric secretion of acid (H2-receptor antagonists or PPIs) will result in a rise in serum gastrin as the feedback inhibition of gastrin release is diminished. Gastrin levels are commonly elevated in patients taking PPIs, but only unusually to a significant degree. No adverse clinical events have been noted with the generally mild hypergastrinemia seen with PPI therapy during the 14 years these compounds have been in clinical use.
Serum B12 levels are in part dependent on the presence of intrinsic factor secreted by parietal cells along with acid and the subsequent binding of intrinsic factor to free cobalamin in the small intestine. PPI use decreases the secretion of acid from parietal cells and of intrinsic factor as well. Studies of B12 levels in patients taking PPIs chronically have demonstrated a clinically insignificant decrease in serum B12 levels, but there have been no reports of B12 deficiency despite 14 years of widespread use of these compounds. If one is concerned about the possibility of B12 deficiency, supplementation of this vitamin can be achieved at little cost. The need for such supplementation has never been demonstrated despite close scrutiny of this physiology over time.
Iron absorption is facilitated in part by the conversion of heme in the presence of acid to a different state. Decreased acid secretion in the presence of PPI therapy theoretically would decrease the presence of this converted iron and could lead to decreased absorption. However, iron malabsorption has never been demonstrated in patients taking PPIs.
Why have there been no clinically adverse events related to these potential physiologic perturbations despite widespread use of PPIs? The answer lies in the extent and duration of the antisecretory therapy with these compounds. In general, most of these agents inhibit acid secretion only for 10-12 hours of the day, meaning that for most of the day, normal acid secretion is taking place and these physiologic events are proceeding as expected. If an agent becomes available that truly results in achlorhydria (absent acid secretion), then these physiologic consequences may become clinically relevant and worth monitoring. Until that time, there is little likelihood of encountering a patient who develops a clinically relevant abnormality of these physiologic processes due to the fact that he or she is taking a PPI.
Posted 03/14/2003
Dr. Fennerty has disclosed that he has received grants for educational activities and has served as an advisor or consultant for AstraZeneca, Merck, Santarus, TAP, and Novartis.
http://www.medscape.com/viewarticle/450444_
Question:
What is the effect of proton-pump inhibitors (PPIs) on serum gastrin levels?...on vitamin B12 levels?...on serum iron levels?
Alan K. Hendra, MD
Response from M. Brian Fennerty, MD
Professor of Medicine, Section Chief of Gastroenterology, Oregon Health Sciences University, Portland, Oregon
The basis for these questions is the fact that levels of all 3 of these substances (hormones, vitamins, and elements) are in some way dependent on or related to gastric acid secretion. As such, any agent that affects gastric acid secretion may affect these specific substances, and because PPIs are potent antisecretory agents, they should in turn affect them to a greater degree.
Gastrin is a potent acid secretagogue that is released from "G" cells in the antrum of the stomach and the duodenum in response to a meal. The feedback inhibition for gastrin is acid present in the lumen of the stomach and small intestine. The use of any agent that inhibits gastric secretion of acid (H2-receptor antagonists or PPIs) will result in a rise in serum gastrin as the feedback inhibition of gastrin release is diminished. Gastrin levels are commonly elevated in patients taking PPIs, but only unusually to a significant degree. No adverse clinical events have been noted with the generally mild hypergastrinemia seen with PPI therapy during the 14 years these compounds have been in clinical use.
Serum B12 levels are in part dependent on the presence of intrinsic factor secreted by parietal cells along with acid and the subsequent binding of intrinsic factor to free cobalamin in the small intestine. PPI use decreases the secretion of acid from parietal cells and of intrinsic factor as well. Studies of B12 levels in patients taking PPIs chronically have demonstrated a clinically insignificant decrease in serum B12 levels, but there have been no reports of B12 deficiency despite 14 years of widespread use of these compounds. If one is concerned about the possibility of B12 deficiency, supplementation of this vitamin can be achieved at little cost. The need for such supplementation has never been demonstrated despite close scrutiny of this physiology over time.
Iron absorption is facilitated in part by the conversion of heme in the presence of acid to a different state. Decreased acid secretion in the presence of PPI therapy theoretically would decrease the presence of this converted iron and could lead to decreased absorption. However, iron malabsorption has never been demonstrated in patients taking PPIs.
Why have there been no clinically adverse events related to these potential physiologic perturbations despite widespread use of PPIs? The answer lies in the extent and duration of the antisecretory therapy with these compounds. In general, most of these agents inhibit acid secretion only for 10-12 hours of the day, meaning that for most of the day, normal acid secretion is taking place and these physiologic events are proceeding as expected. If an agent becomes available that truly results in achlorhydria (absent acid secretion), then these physiologic consequences may become clinically relevant and worth monitoring. Until that time, there is little likelihood of encountering a patient who develops a clinically relevant abnormality of these physiologic processes due to the fact that he or she is taking a PPI.
Posted 03/14/2003
Dr. Fennerty has disclosed that he has received grants for educational activities and has served as an advisor or consultant for AstraZeneca, Merck, Santarus, TAP, and Novartis.
http://www.medscape.com/viewarticle/450444_