Micronutrient Deficiency Often Unnoticed in PPI Users

Megan Brooks

October 19, 2016

Although patients on long-term proton pump inhibitor (PPI) therapy are at increased risk for micronutrient deficiency, clinicians aren't routinely checking for this, even in high-risk patients, according to results from a small British study.

"It was quite startling, really," said Tareq El Menabawey, a gastroenterology registrar at Barnet Hospital, Royal Free NHS Trust, in London, United Kingdom.

"We had some patients who have been followed up for the better part of a decade, and nearly 50% have never had any blood tests for micronutrients," he told Medscape Medical News.

The study findings were reported in a poster at United European Gastroenterology Week in Vienna.

"In the United Kingdom, as in the United States, PPI prescription is massively widespread and quite often not indicated, and there is increasing concern about safety," Dr El Menabawey said.

Although they are generally quite safe, PPIs have been associated with Clostridium difficile infection and with micronutrient deficiency. "Our hypothesis was that even though gastroenterologists know about micronutrient deficiency, they aren't looking for it," he explained.

It was quite startling, really.

The researchers reviewed the electronic health records of 41 patients with Barrett's esophagus who were on long-term PPI therapy to see if their levels of vitamin B₁₂, ferritin, or magnesium were ever tested. The cohort involved 27 men (average age, 66 years) and 14 women (average age, 73 years).

The micronutrient levels of 20 patients (48.8%) had not been tested in the previous 5 years. Only a single patient had undergone micronutrient testing in the previous 12 months. And six patients (14.6%) had an incidental micronutrient deficiency detected on routine blood testing (vitamin B₁₂, folate, phosphate, ferritin).

Serum magnesium level was not checked in the previous year for 38 patients (92.7%), and had never been checked for 15 patients (36.6%).

Serum ferritin and vitamin B₁₂ levels were not checked in the previous year for 32 patients (78.1%), and had never been checked for nine patients (21.5%).

The median level of magnesium in the study cohort was at the low end of normal, and median ferritin level was normal. There was one case of vitamin B₁₂ deficiency (2.4% of all patients; 31.3% of all those tested). Median serum B₁₂ level was normal.

"Even in this small cohort, magnesium and B₁₂ deficiency was detected," Dr El Menabawey and his colleagues report. And "given the low level of investigation," deficiencies might even be larger.

There are reports in the literature of "serious" problems from PPI-induced micronutrient deficiency, including seizures and cardiac arrhythmias secondary to hypomagnesemia, Dr El Menabawey told Medscape Medical News.

The US Food and Drug Administration lists hypomagnesemia as a potential adverse effect of PPI therapy, and recommends that clinicians consider monitoring serum magnesium in long-term users.

More Study Needed

Given the widespread use of PPIs, "there is a clinical need to definitively ascertain the link with micronutrient deficiencies," the researchers conclude. And more research is needed to understand the role of screening to identify those requiring supplementation.

This is a single-center study with a very small sample size, "so it's a little hard to draw any firm conclusions," said Yu-Xiao Yang, MD, associate professor of epidemiology and gastroenterology at the Perelman School of Medicine in Philadelphia.

"From the standpoint of practice patterns, it's not a surprise that very few patients receiving chronic PPI therapy underwent monitoring for these micronutrients, because there is no recommendation to do so," he told Medscape Medical News.

Although micronutrient deficiency with PPIs is "pretty well recognized, all the data come from observational studies," Dr Yang pointed out. "This can be a problem because long-term users may be different from nonusers. When you observe a lower level of these nutrients in PPI users, it's hard to tell whether it's from the PPI or whether it's just who they are. Without really having that aspect pinned down, it's going to be hard for any guideline to come out and recommend definitively to monitor micronutrients."

The study had no commercial funding. Dr El Menabawey and Dr Yang have disclosed no relevant financial relationships.

United European Gastroenterology (UEG) Week: Poster P0533. Presented October 17, 2016.


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