This transcript has been edited for clarity.
In this podcast, I’m going to talk about hypomagnesemia in primary care, or low magnesium levels. Now, it’s fair to say that most of us in primary care rarely think about testing serum magnesium levels. However, low magnesium can be serious and potentially fatal in the presence of a severe deficiency. Additionally, there’s an established relationship between hypomagnesemia and the use of proton pump inhibitors (PPIs), which are widely prescribed in primary care, and I will talk about this shortly.
So, what is the role of magnesium in our bodies? Well, magnesium is a cofactor in enzyme systems involving energy metabolism and protein synthesis. Magnesium also plays a role in the active transport of calcium and potassium across cell membranes and is pivotal to nerve impulse conduction, muscle contraction, and the maintenance of a regular heart rhythm.
Now, normal ranges of serum magnesium are around about 0.7-1.0 mmol/L. A mild deficiency is generally classified as 0.5-0.7 mmol/L, a moderate deficiency as 0.4-0.5 mmol/L, and severe deficiency as less than 0.4 mmol/L. Once again, hypomagnesemia can be serious and potentially fatal in severe deficiency. That said, most individuals are asymptomatic, with symptoms usually not apparent until magnesium levels are less than 0.5 mmol/L. A moderate deficiency with symptoms, or severe deficiency, usually requires hospital assessment and intravenous magnesium replacement.
So, what are the risk factors or causes for hypomagnesemia? Magnesium can be lost from the gastrointestinal system in the presence of acute or chronic diarrhea in malnutrition states or malabsorption, including celiac disease. Acute pancreatitis can also lead to low magnesium levels, as can laxative misuse and eating disorders, including anorexia nervosa. Magnesium can also be lost via the kidneys in the context of alcohol dependence, diabetes and diabetic ketoacidosis, and after acute kidney injury or AKI. Finally, there are many commonly prescribed medications that can lead to low magnesium levels, including PPIs (as I’ve mentioned already), loop and thiazide diuretics, digoxin, gentamicin, salbutamol, immunosuppressants, and chemotherapy agents. Hypomagnesemia also increases the risk of digoxin toxicity.
What are the clinical manifestations of low magnesium levels, then? Well, low magnesium levels can lead to neuromuscular effects, including muscular weakness, ataxia, tremor, and spasms of the hands and feet. Cardiovascular effects include ECG abnormalities, such as widening of the QRS complex, and ventricular arrhythmias such as torsade de pointes. Low magnesium levels are also often associated with hypocalcemia and hypokalemia. Other effects include fatigue, dizziness, nausea, vomiting, and confusion.
Finally, let’s discuss investigation and management. For an asymptomatic or mild hypomagnesemia, we simply need to review the individual for any underlying causes, and often this will be secondary to recent gastrointestinal loss from diarrhea or secondary to medications. If appropriate, stop any offending medications or seek specialist advice if the drug cannot immediately be stopped.
Individuals with risk factors for hypomagnesemia, especially if they’re also taking digoxin or have evidence of low calcium or low potassium levels, should be considered for infrequent magnesium monitoring. As mentioned, prolonged treatment (usually over 1 year) with all PPIs can lead to hypomagnesemia, and do remember to take into account any over the counter use of PPIs.
Now, there is a dose-response relationship evident here. Higher doses of PPIs for a longer duration of time are more likely to lead to low magnesium levels. This hypomagnesemia usually resolves within a few weeks of cessation of the PPI. So, if the PPI is the culprit, review the need for a PPI and consider switching to a histamine antagonist such as famotidine, nizatidine, or cimetidine. For those who do continue long-term PPI therapy, intermittent monitoring of magnesium levels may be prudent, especially in those coprescribed digoxin and or diuretics.
With regard to magnesium replacement, we need to give advice to individuals regarding magnesium-containing foods. Green leafy vegetables, dairy foods, nuts, whole grain pasta and bread, fish, pulses, baked beans, seafood, and brown rice are all good dietary sources of magnesium. Oral magnesium replacement should be considered in the presence of risk factors for hypomagnesemia and/or an unwell individual. The usual dose for magnesium replacement is 15-24 mmol/day in divided doses.
Now, we should be aware that magnesium supplementation can cause gastrointestinal disturbance, particularly diarrhea. So, do advise individuals to take their magnesium supplements with meals and to have clear separation of dosing. Furthermore, if estimated glomerular filtration rate is less than 30 mL/min, we should seek advice from our kidney colleagues, as there’s a high risk of rebound hypermagnesemia or high magnesium levels.
Lastly, reversal of low magnesium levels can take up to 6-8 weeks with oral magnesium supplementation. We should stop oral magnesium supplements around 1-2 days after serum magnesium levels have normalized, as intracellular magnesium stores do take longer to replete.
Although most patients with hypomagnesemia are asymptomatic, severe magnesium deficiency can be fatal.
