Evidence for using magnesium supplements with PPI therapy
Magnesium deficiency or ‘hypomagnesaemia’ has been associated with long-term use of proton pump inhibitors (PPIs). Case reports indicate that stopping the PPI is the best way to normalise magnesium levels. Taking a magnesium supplement with the PPI may not be enough to correct the magnesium deficiency.
Limitations of evidence
No studies have investigated the use of a magnesium supplement to prevent magnesium deficiency during PPI therapy. A magnesium supplement should only be considered if a PPI has caused a deficiency in magnesium that requires treatment. Evidence for using a supplement with a PPI to treat magnesium deficiency is based on case reports.
Cases of magnesium deficiency with PPI therapy have been reported in the literature and to regulatory authorities worldwide.1–13 The first published reports were in 2006, based on 2 Australian cases of severe magnesium deficiency with omeprazole.2,3
Up to March 2011, the Therapeutic Goods Administration (TGA) in Australia had received 6 reports of hypomagnesaemia with PPIs.2 In 2011 the US Food and Drug Administration (FDA) issued a safety announcement about this potential adverse effect following a review of published cases and 38 cases reported in their Adverse Event Reporting System.4
The first cases published in 2006 had received high-dose magnesium supplementation for a few months while continuing omeprazole.3 Stopping the PPI normalised magnesium levels rapidly without the need for further supplementation.3
Further cases also reported to have resolved after stopping the PPI, generally within 1–2 weeks.1,5 Magnesium levels usually dropped again when therapy was restarted or switched to another PPI, while substitution with a histamine-2 receptor antagonist like ranitidine brought levels back to normal.1–5,7–11,13
Magnesium supplementation while continuing PPI therapy was at best only partly effective in resolving the cases of deficiency, even after months of treatment.1,3,5–7,10–13 More than a quarter of cases reviewed by the FDA did not improve with supplementation alone.4
People who may be deficient in magnesium or at risk should see their doctor first
People should be referred to their doctor if they have symptoms of deficiency, or if they’ve been on long-term PPI therapy and may need their magnesium levels checked.
This is particularly important for people at high risk of magnesium deficiency from other causes — these include gastrointestinal conditions, such as inflammatory bowel disease and chronic pancreatitis, and medicines like digoxin and loop and thiazide diuretics.14
Seeing a doctor also provides an opportunity to review the need for ongoing PPI therapy and whether this can be stepped down or stopped.
While predictors of magnesium deficiency with PPIs are yet to be established, reported cases mostly occurred after continuous long-term therapy for at least 12 months (usually more than 5 years) and were largely unrelated to dose.1–13 Certain conditions or medicines may also have contributed to the magnesium deficiency in some of the cases.1,4
Magnesium deficiency can cause non-specific symptoms like nausea, tiredness or confusion, and some people don’t get any symptoms.1,2,14 Severe cases are usually easier to recognise when symptoms like muscle spasms, convulsions, and irregular heart beats (arrhythmias) occur.1,2,14
A doctor will manage underlying causes(s) of magnesium deficiency in addition to supplementation.14 Intravenous rather than oral magnesium may be necessary for some people, especially if the deficiency is severe or causing considerable symptoms.14
Supplements can have side effects and interactions
Side effects with magnesium, particularly diarrhoea, may be an issue for some people, especially if they need high oral doses to help treat a deficiency.1,5,14
Magnesium supplements can also affect the absorption of certain medicines (including tetracycline antibiotics and bisphosphonates used for osteoporosis) so they need to be taken at least 2 hours apart from these other medicines.
- Cundy T, Mackay J. Proton pump inhibitors and severe hypomagnesaemia. Curr Opin Gastroenterol 2011;27:180–5. www.ncbi.nlm.nih.gov/pubmed/20856115
- Therapeutic Goods Administration. Medicines Safety Update Volume 2, Number 3, June 2011. www.australianprescriber.com/magazine/34/3/81/4 (accessed 27 September 2011)
- Epstein M, McGrath S, Law F. Proton-pump inhibitors and hypomagnesemic hypoparathyroidism. N Engl J Med 2006;355:1834–6. www.ncbi.nlm.nih.gov/pubmed/17065651
- U.S. Food and Drug Administration. FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs). www.fda.gov/drugs/drugsafety/ucm245011.htm (accessed 27 September 2011)
- Mackay JD, Bladon PT. Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series. QJM 2010;103:387–95. www.ncbi.nlm.nih.gov/pubmed/20378675
- Cundy T, Dissanayake A. Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrinol (Oxf) 2008;69:338–41. www.ncbi.nlm.nih.gov/pubmed/18221401
- Shabajee N, Lamb EJ, Sturgess I, et al. Omeprazole and refractory hypomagnesaemia. BMJ 2008;337:a425. doi: 10.1136/bmj.39505.738981.BE. www.ncbi.nlm.nih.gov/pubmed/18617497
- Kuipers MT, Thang HD, Arntzenius AB. Hypomagnesaemia due to use of proton pump inhibitors — a review. Neth J Med 2009;67:169–72. www.ncbi.nlm.nih.gov/pubmed/19581665
- Broeren MA, Geerdink EA, Vader HL, et al. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med 2009;151:755–6. www.ncbi.nlm.nih.gov/pubmed/19920278
- Hoorn EJ, van der Hoek J, de Man RA, et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis 2010;56:112–6. www.ncbi.nlm.nih.gov/pubmed/20189276
- Regolisti G, Cabassi A, Parenti E, et al. Severe hypomagnesemia during long-term treatment with a proton pump inhibitor. Am J Kidney Dis 2010;56:168–74. www.ncbi.nlm.nih.gov/pubmed/20493607
- Furlanetto TW, Faulhaber GA. Hypomagnesemia and proton pump inhibitors: below the tip of the iceberg. Arch Intern Med 2011;171:1391–2. www.ncbi.nlm.nih.gov/pubmed/21555654
- Quasdorff M, Mertens J, Dinter J, et al. Recurrent hypomagnesemia with proton-pump inhibitor rechallenge. Ann Intern Med 2011;155:405–7. www.ncbi.nlm.nih.gov/pubmed/21930865
- Wu J. Magnesium: the forgotten electrolyte. Aust Prescr 2007; 30:102–5. www.australianprescriber.com/magazine/30/4/102/5 (accessed 26 September 2011)