Proton pump inhibitors: Watch out for the possible Iron deficiency!

Proton Pump Inhibitor Antacid Medications linked to Iron Deficiency

Iron deficiency is an important issue for hair specialists to know about given that iron deficiency can trigger hair loss in some patients.

I was interested to read a meta-analysis in the March 2022 issue of Current Reviews in Clinical and Experimental Pharmacology examining the relationship between proton pump inhibitor drugs and the risk of iron deficiency anemia.

The author evaluated 14 studies examining the relationship between PPI’s and iron deficiency anemia. The author showed that there was a 2.56 fold increased risk of iron deficiency anemia in users of PPIs (RR 2.56 [95% CI 1.43-4.61], p < 0.00001).

Proton pump inhibitors (PPIs) are commonly used in the population to treat a variety of acid related problems. New data supports the notion that PPIs may contribute to iron deficiency anemia.

Summary and Comment

Proton pump inhibitors are among the most commonly prescribed drugs worldwide. These drugs irreversibly inhibit H+/K+ adenosine triphosphatase pumps in gastric parietal cells and results in the suppression of gastric acid production. The FDA approved the drugs for many indications including gastroesophageal reflux disease (GERD), duodenal or gastric ulcers, Helicobacter pylori infections, and Zollinger-Ellison syndrome and prevention of nonsteroidal anti-inflammatory drug (NSAID)-associated gastrointestinal lesions in at-risk patients.

Side Effects and Concerns with Long Term PPI Use

A number of safety concerns continue to be studied including the link between PPI use and bone fractures, renal toxicities, infections, and micronutrient deficiencies (iron and magnesium, calcium and B12 and zinc), cancer, and gut microbiome disruption. By raising pH of the stomach they also affect how some drugs get absorbed so there are important drug -drug interactions. Some of the links are weak and some are strong. For example, it is now widely accepted that PPI use is a risk factor for the development of osteoporosis and osteoporotic fractures.

In terms of iron deficiency, it could be that different PPI’s carry different risks for iron deficiency. In a meta-analysis including 57 clinical studies, the potency of different PPIs was compared using intragastric pH-monitoring data. Compared with omeprazole (equivalent of 1.0), the relative potencies were 0.23 for pantoprazole, 0.90 for lansoprazole, 1.60 for esomeprazole, and 1.82 for rabeprazole. There does seem to be some evidence that less potent PPI’s have a lower risk for causing iron deficiency.

Summary

In summary, iron deficiency is an important issue to be aware of in those using PPIs. My standard blood tests panels always include ferritin, B12, zinc and magnesium in patients with hair loss who also use PPI medications.

MAIN REFERENCE

Ali MD. Proton pump inhibitors' use and risk of iron deficiency anaemia: a systematic review and meta-analysis. Curr Rev Clin Exp Pharmacol. 2022 Mar 7. doi: 10.2174/2772432817666220307121220. Online ahead of print.

ADDITIONAL REFERENCES
Douwes et al. Type of proton-pump inhibitor and risk of iron deficiency in kidney transplant recipients - results from the TransplantLines Biobank and Cohort Study. Transpl Int. 2021 Nov;34(11):2305-2316.

Forgacs, I.; Loganayagam, A. Overprescribing proton pump inhibitors. BMJ 2008, 336, 2–3.

Kirchheiner J, Glatt S, Fuhr U, et al. Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH. Eur J Clin Pharmacol 2009; 65: 19.

Vaezi, M.F.; Yang, Y.X.; Howden, C.W. Complications of Proton Pump Inhibitor Therapy. Gastroenterology 2017, 153, 35–48.

Yibirin, M., De Oliveira, D., Valera, R., Plitt, A. E., and Lutgen, S. (2021). Adverse Effects Associated with Proton Pump Inhibitor Use. Cureus 13 (1), e12759. doi:10.7759/cureus.12759