Iron deficiency

Antacids as a Risk and the Cause of Iron Deficiency Anemia

The term “antacids” is used to describe certain compounds that neutralize stomach acids, such as Tums, Maalox, Mylanta, and others. They directly neutralize the stomach acid and contain various forms of calcium, magnesium, and aluminum as active ingredients. Other drugs work by reducing the stomach production of acid (H2 blockers and proton pump inhibitors). Antacids can interfere with the absorption of iron, zinc, and other minerals by neutralizing stomach acid. Research suggests that antacids physically bind to folate and reduce its absorption by the body. Antacids that contain calcium may also compete for absorption with iron and impair iron absorption. Studies have shown that sodium bicarbonate and calcium carbonate causes the plasma iron to be increase to be 50% and 67% less than the control values. Another study shows that both calcium carbonate and aluminum hydroxide markedly reduce the amount of iron retained by the body.


PPI –Short Overview

The introduction of PPI (proton-pump inhibitors) into clinical routine practice happened almost 30 years ago. These medications are widely used in different countries treating wide range of acid-related problems, such as: heartburn, gastritis, ulcers, gastroesophageal reflux disease, Barrett’s esophagus. All of the members of this class of drugs share similar mechanism ofaction, by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells. The proton pump is the terminal stage in the secretion of Hydrochloric Acid into the stomach lumen, making it the ideal target for acid secretion inhibiting.

PPI –safety issues

Although generally regarded as safe class of medications, in USA FDA has advised that no more than three 14-day treatment courses should be used in one year. In general, short-term use of PPI is well-tolerated, with relatively low incidence of side effects. These usually involve: headache, nausea, diarrhea, abdominal pain, fatigue and dizziness. Long-term use of PPI should always consider the balance between benefits and risks of the therapy. Clinical reviews on PPI long-term use recommend that PPIs should be used at the lowest effective dose in people with a proven indication, but discourage dose escalation and continued chronic therapy in people unresponsive to initial empiric therapy.


PPI and Nutritional status of some important vitamins and minerals

One of the quite important drawbacks of PPI use is their influence on status of certain nutritional ingredients. There are publications in the scientific literature showing reduction of Vitamin B12, Magnesium, Calcium in patients on PPI therapy. This reduction is mainly considered to be the consequence of changing the pH-status in gastrointestinal system, influencing the absorption of these certain ingredients. Vitamin B12 reduced levels have a detrimental influence on the function of different systems and organs in our body, such as central and peripheral nervous system function, production of red blood cells. Reduction in calcium absorption can lead to increased risk of fractures. Regarding MAGNESIUM, FDA issued the warning in February 2011, indicating that PPI-use is associated with hypomagnesemia. This phenomenon can cause different symptoms in the organism, including leg cramps, headache and others.


PPI, H2-receptor antagonists and IRON DEFFICIENCY

Lately, more and more publications raise the concern about PPI use and iron levels in the blood. A new study (Journal of Internal Medicine, 2018) from UK on more than 26,500 participants showed that there is a risk of more than 3.6 times to develop iron deficiency anemia in patients on chronic PPI therapy (>12 months) in comparison with non-PPI users and there is more than 1.5 time risk of iron deficiency anemia in intermittent (on-off) PPI users in comparison with non-users. Another study made on more than 450,000 (77 thousand newly diagnosed patients with iron deficiency vs 389,000 controls) participants covering a 15 year span (1999-2013) from USA, published in 2017 in the journal – GASTROENTEROLOGY, showed similar results: patients on PPI chronic therapy (more than 24 months) exhibited the 2.5-time higher risk of iron deficiency in comparison with non-users. PPI is not the only class of acid-lowering medications influencing the iron status in the body. The use of H2-antagonists (famotidine, ranetidine) was also shown as a risk factor for developing of Iron deficiency. The use of more than 2 years of H2-receptor antagonists is associated with the risk of more than 50% to develop iron deficiency in comparison to the non-users.

Apart with time-dependent risk of developing iron deficiency, a dose dependency also exist. The larger the daily dose of PPI taken (the base dose was Omeprazole 20mg once daily) –the higher the risk of developing IRON deficiency anemia. The exact mechanism behind the influence of PPI on absorption rate of iron in GI tract is not yet fully elucidated. However, by increasing the pH levels in PPI-treated patients, there is the decrease in the reduction of iron into it’s most bioavailable form –ferrous iron (Fe2+), and subsequently reduction in absorption efficiency and rate. Special populations who should be closely monitored in terms of their iron levels while on PPI, are elderly people and women of child-bearing age, who might plan their pregnancy, a period inlife when sufficient level of iron is of very high importance. Since there are medical conditions requiring long-term PPI use, there is a need for solutions preventing and minimizing the risks of Iron deficiency anemia.

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