{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:20:27Z","timestamp":1791602427235,"version":"4.3.4"},"reference-count":317,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIDDK intramural program","award":["NIDDK #DK053200-26"],"award-info":[{"award-number":["NIDDK #DK053200-26"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger\u2013Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence\/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p &lt; 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH &gt; 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.<\/jats:p>","DOI":"10.3390\/ijms25137286","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Long-Term Proton Pump Inhibitor\u2013Acid Suppressive Treatment Can Cause Vitamin B12 Deficiency in Zollinger\u2013Ellison Syndrome (ZES) Patients"],"prefix":"10.3390","volume":"25","author":[{"given":"Tetsuhide","family":"Ito","sequence":"first","affiliation":[{"name":"Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Ramos-Alvarez","sequence":"additional","affiliation":[{"name":"Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5009\/gnl15502","article-title":"25 Years of Proton Pump Inhibitors: A Comprehensive Review","volume":"11","author":"Strand","year":"2017","journal-title":"Gut Liver"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"182","DOI":"10.5056\/jnm18001","article-title":"Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use","volume":"24","author":"Kinoshita","year":"2018","journal-title":"J. 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