This letter to the Editor was published in the November 2001 issue of Parkhurst Exchange, p7<\/p>\n
Gentlemen:<\/p>\n
In the June 2001 issure of Parkhurst Exchange, your consultant AS
\nreported no serious side effects from the longterm use of pantoprazole,
\nto his knowledge.<\/p>\n
Gastric acid suppressive therapy in general has been shown to suppress
\nthe absorption of vitamin B12 from food, because the release of B12 from
\nfood proteins requires the presence of gastric acid. Thus longterm use
\nof proton pump inhibitors such as omeprazole and probably pantoprazole
\nmay lead to vitamin B12 deficiency, which can have serious and
\npotentially irreversible neurologic consequences, in addition to
\nhematologic and gastrointestinal problems.<\/p>\n
I would suggest that any individual on medication which suppresses
\ngastric acid production also take a daily vitamin supplement containing
\nsynthetic vitamin B12.<\/p>\n
References:<\/p>\n
1. Bradford GS, Taylor CT. Omeprazole and vitamin B12 deficiency.
\nAnnals of Pharmacotherapy 1999;33(5):641-3.
\nAbstract: The mainstay for cobalamin deficiency is correction of the
\nunderlying disorder and replacement therapy. Because the defect is often
\none of absorption, parenteral or intranasal routes are recommended. In
\nmost cases, replacement therapy is all that is needed. The vitamin
\npreparation most commonly used is cyanocobalamin (also called vitamin
\nB12), which has no known physiologic role but instead is converted to a
\nbiologically active form before it can be used by tissues. The studies
\nreviewed in this article clearly show that omeprazole therapy will
\ndecrease the absorption of vitamin B12 by preventing its cleavage from
\ndietary proteins. However, these data are insufficient to infer that
\nclinically significant deficiency will occur over time. In fact, some of
\nthe studies suggest that the simple addition of juices or other acidic
\ndrinks into the diet may dramatically increase cobalamin absorption.
\nClearly, well-designed clinical trials are needed to evaluate this
\ntheory over an extended follow-up period to determine the clinical
\nsignificance of omeprazole-associated vitamin B12 deficiency and
\npossibly identify patients at risk for deficiency. In conclusion, the
\npossibility of dietary vitamin B12 malabsorption should be considered in
\npatients receiving chronic omeprazole treatment and presenting with
\nsigns and symptoms of deficiency. All healthcare workers should be made
\naware of the potential clinical complications of omeprazole-associated
\nvitamin B12 deficiency since it may go unrecognized and is easily
\ncorrected. This is particularly relevant for elderly patients with poor
\ndietary intake of vitamin B12, impaired vitamin B12 stores, and certain
\ngastrointestinal disorders.<\/p>\n
2.\tTermanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric
\nacid suppressive therapy on serum vitamin B12 levels in patients with
\nZollinger-Ellison syndrome. Am. J. Med. 1998;104(5):422-30.
\nAbstract: BACKGROUND AND AIMS: Long-term treatment with H(+)-K(+)-
\nadenotriphosphatase (ATPase) inhibitors, such as omeprazole or
\nlansoprazole, for severe gastroesophageal reflux disease is now widely
\nused. Whether such treatment will result in vitamin B12 deficiency is
\ncontroversial. We studied whether long-term treatment with omeprazole
\nalters serum vitamin B12 levels in patients with Zollinger-Ellison
\nsyndrome. METHODS: In 131 consecutive patients treated with either
\nomeprazole (n = 111) or histamine H2-receptor antagonists (n = 20),
\nserum vitamin B12 and folate levels and complete blood counts were
\ndetermined after acid secretion had been controlled for at least 6
\nmonths. These studies were repeated yearly. Serum vitamin B12 and folate
\nlevels were correlated with the type of antisecretory drug and the
\nextent of inhibition of acid secretion. RESULTS: The mean duration of
\nomeprazole treatment was 4.5 years, and for H2-receptor antagonists 10
\nyears. Vitamin B12 levels, but not serum folate levels or any
\nhematological parameter, were significantly (P = 0.03) lower in patients
\ntreated with omeprazole, especially those with omeprazole- induced
\nsustained hyposecretion (P = 0.0014) or complete achlorhydria (P
\n0.0001). In 68 patients with two determinations at least 5 years apart,
\nvitamin B12 levels decreased significantly (30%; P = 0.001) only in
\npatients rendered achlorhydric. The duration of omeprazole treatment was
\ninversely correlated with vitamin B12 levels (P = 0.013), but not folate
\nlevels. Eight patients (6%) developed subnormal B12 levels during
\nfollow-up. CONCLUSIONS: Long-term omeprazole treatment leads to
\nsignificant decreases in serum vitamin B12 but not folate levels. These
\nresults suggest patients with Zollinger-Ellison syndrome treated with
\nH(+)-K(+)-ATPase inhibitors should have serum vitamin B12 levels
\nmonitored. Furthermore, these results raise the possibility that other
\npatients treated chronically with H(+)-K(+)-ATPase inhibitors may
\ndevelop B12 deficiency.<\/p>\n
3.\tThorens J, Froehlich F, Schwizer W, et al. Bacterial overgrowth
\nduring treatment with omeprazole compared with cimetidine: a prospective
\nrandomised double blind study. Gut 1996;39(1):54-9.
\nAbstract: BACKGROUND: Gastric and duodenal bacterial overgrowth
\nfrequently occurs in conditions where diminished acid secretion is
\npresent. Omeprazole inhibits acid secretion more effectively than
\ncimetidine and might therefore more frequently cause bacterial
\novergrowth. AIM: This controlled prospective study compared the
\nincidence of gastric and duodenal bacterial overgrowth in patients
\ntreated with omeprazole or cimetidine. METHODS: 47 outpatients with
\npeptic disease were randomly assigned to a four week treatment regimen
\nwith omeprazole 20 mg or cimetidine 800 mg daily. Gastric and duodenal
\njuice were obtained during upper gastrointestinal endoscopy and plated
\nfor anaerobic and aerobic organisms. RESULTS: Bacterial overgrowth (> or
\n= 10(5) cfu\/ml) was present in 53% of the patients receiving omeprazole
\nand in 17% receiving cimetidine (p 0.05). The mean (SEM) number of
\ngastric and duodenal bacterial counts was 6.0 (0.2) and 5.0 (0.2)
\nrespectively in the omeprazole group and 4.0 (0.2) and 4.0 (0.1) in the
\ncimetidine group (p 0.001 and 0.01; respectively). Faecal type bacteria
\nwere found in 30% of the patients with bacterial overgrowth. Basal
\ngastric pH was higher in patients treated with omeprazole compared with
\ncimetidine (4.2 (0.5) versus 2.0 (0.2); p 0.001) and in patients with
\nbacterial overgrowth compared with those without bacterial overgrowth
\n(5.1 (0.6) versus 2.0 (0.1); p 0.0001). The nitrate, nitrite, and
\nnitrosamine values in gastric juice did not increase after treatment
\nwith either cimetidine or omeprazole. Serum concentrations of vitamin
\nB12, beta carotene, and albumin were similar before and after treatment
\nwith both drugs. CONCLUSIONS: These results show that the incidence of
\ngastric and duodenal bacterial overgrowth is considerably higher in
\npatients treated with omeprazole compared with cimetidine. This can be
\nexplained by more pronounced inhibition of gastric acid secretion. No
\npatient developed signs of malabsorption or an increase of N-nitroso
\ncompounds. The clinical significance of these findings needs to be
\nassessed in studies with long-term treatment with omeprazole, in
\nparticular in patients belonging to high risk groups such as HIV
\ninfected and intensive care units patients.<\/p>\n
4.\tBatzri S, Brugada O, Harmon JW, Rich NM. Inhibition of acid secretion
\nin guinea pigs by tricyclic antidepressants: comparison with ranitidine
\nand omeprazole. J. Pharmacol. Exp. Ther. 1988;246(2):493-9.
\nAbstract: The antisecretory properties of imipramine on gastric
\nsecretion in guinea pig in comparison with other antisecretory agents
\nwas determined. In awake guinea pigs s.c. infusion of histamine (30
\nmicrograms\/kg\/hr) increased acid and fluid secretion by 3- to 4-fold.
\nWhen acid output peaked, a bolus administration of the tricyclic anti-
\ndepressant imipramine inhibited acid and fluid secretion. Imipramine and
\nother agents, such as ranitidine and omeprazole, inhibited gastric
\nsecretion in a dose-dependent fashion. The most potent was the H2-
\nantagonist ranitidine (IC50, 0.2-0.3 mumol\/kg), followed by the gastric
\nH-K-adenosine triphosphatase inhibitor, omeprazole (IC50, 0.5-0.6
\nmumol\/kg). Imipramine (IC50 1-2 mumol\/kg) was the least potent of the
\ninhibitors. Both ranitidine and omeprazole could abolish acid secretion,
\nbut maximal inhibition with imipramine was 60% of initial. Promethazine
\n(25 mumol\/kg), an H1 antagonist, and atropine (12 mumol\/kg), a
\nmuscarinic antagonist, inhibited gastric secretion by 40 to 50%.
\nImipramine and atropine also inhibited basal acid secretion. In
\ndispersed gastric cells comparison between imipramine and omeprazole
\nshowed that imipramine was about 5-fold more potent than omeprazole in
\nblocking histamine or dibutyryl cyclic AMP stimulation of aminopyrine
\naccumulation. Imipramine probably acts as a protonophore by increasing
\nthe rate of proton-gradient dissipation rather than by interfering with
\nthe hydrogen-pump system because, in gastric membranes, imipramine was
\n20-fold less potent than omeprazole in inhibiting the gastric H-K-
\nadenosine triphosphatase activity. These results suggest that imipramine
\nadministered s.c. in guinea pigs is a potent antisecretory drug. Its
\naction may be due to a combination of anticholinergic and antihistamine
\nH2 activities.<\/p>\n
5.\tSaltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due
\nto omeprazole treatment or atrophic gastritis on protein-bound vitamin
\nB12 absorption [see comments]. J. Am. Coll. Nutr. 1994;13(6):584-91.
\nAbstract: OBJECTIVE: To investigate the effects of hypochlorhydria and
\nacidic drink ingestion on protein-bound vitamin B12 absorption in
\nelderly subjects. METHODS: Absorption of protein-bound vitamin B12 was
\nexamined in elderly normal subjects (n = 8), and in hypochlorhydric
\nsubjects due to omeprazole treatment (n = 8) or with atrophic gastritis
\n(n = 3). Subjects underwent absorption tests of protein-bound vitamin
\nB12 ingested with water, cranberry juice and 0.1 N hydrochloric acid.
\nRESULTS: Protein-bound vitamin B12 absorption was lower in the
\nomeprazole-treated group (0.50%) compared to the normal group (1.21%; p
\n0.001). With cranberry juice ingestion, the omeprazole-treated group
\nshowed an increase in absorbed protein-bound vitamin B12 (p = 0.025).
\nWith dilute hydrochloric acid ingestion, there was a further increase in
\nvitamin B12 absorption (p 0.001). CONCLUSION: Omeprazole causes
\nprotein-bound vitamin B12 malabsorption, and ingestion of an acidic
\ndrink improves protein-bound vitamin B12 absorption.<\/p>\n
—
\nHenry Olders, MD, FRCPC
\nSMBD – Jewish General Hospital, 5 East
\n3755 Cote Saint Catherine
\nMontreal, Quebec H3T 1E2
\nCANADA<\/p>\n
514-340-8222 x5881<\/p>\n","protected":false},"excerpt":{"rendered":"
This letter to the Editor was published in the November 2001 issue of Parkhurst Exchange, p7 Gentlemen: In the June 2001 issure of Parkhurst Exchange, your consultant AS reported no serious side effects from the longterm use of pantoprazole, to his knowledge. Gastric acid suppressive therapy in general has been… <\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[87],"tags":[12,415,414],"class_list":["post-1160","post","type-post","status-publish","format-standard","hentry","category-letters","tag-b12","tag-pantoprazole","tag-proton-pump-inhibitors"],"_links":{"self":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1160","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1160"}],"version-history":[{"count":1,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1160\/revisions"}],"predecessor-version":[{"id":1161,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1160\/revisions\/1161"}],"wp:attachment":[{"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1160"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1160"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/henry.olders.ca\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1160"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}