Magnesium supplementation has been shown to inhibit crystal formation, thus reducing the risk of kidney stone formation. The electrolyte works through 3 proposed mechanisms: 1) binding oxalate in the gastrointestinal tract, preventing its absorption, 2) binding oxalate in urine to outcompete its interaction with calcium and 3) chelating with citrate, preventing its resorption to increases urinary citrate levels.¹

While these mechanisms may appear ideal for the prevention of stone formation, the implementation of this agent into the stone prevention armamentarium has not been successful. First, the oral formulation of magnesium oxide and hydroxide are poorly absorbed. When taken on an empty stomach, there is little to no change in urinary magnesium, although this does improve nominally when taken with meals. Second, magnesium supplementation is known to cause diarrhea, which significantly limits its tolerability.² Third, foods high in magnesium also tend to have high oxalate levels, which negates the benefits of the magnesium. Fourth, compliance with preventive medication remains challenging in this population, as exemplified by potassium citrate with adherence rates as low as 13% and an average retail cost of $154.80 for a 1-month supply.³

Table. Stone supplements with magnesium. Adapted from Stern et al.⁷

BID, twice a day. mEq, milliequivalent.

Despite these limitations, clinical evaluation of magnesium has demonstrated equivocal results. For example, Eisner et al were able to demonstrate that an increased magnesium intake was associated with decreasing hyperoxaluria in patients on a retrospective review of 24-hour urinalysis.⁴ Yet a prospective, double-blind, randomized, controlled trial conducted by Ettinger et al to examine the effectiveness of magnesium hydroxide in the prevention of calcium oxalate stones failed to show a difference. In this study, a total of 82 patients taking magnesium oxide supplements (650 mg or 1,300 mg) or placebo were included.⁵ No difference was observed in the recurrence rate between the 2 groups.

While magnesium alone may not have a large clinical impact, utilization of potassium citrate and magnesium together has previously been shown to decrease stone formation. Ettinger et al demonstrated that the combination of potassium citrate/magnesium citrate as compared to placebo reduced stone recurrence by 95% in the calcium stone group. Urine citrate excretion increased from 587 to 769 mg per day, while pH changed from 6.01 to 6.29 in 24-hour urine collections.⁶ Importantly, gastrointestinal side effects of the potassium citrate/magnesium citrate combination were not significantly different from placebo.

Despite the equivocal results in idiopathic stone formers, there are specific circumstances where magnesium supplementation is indicated due to the underlying pathophysiology of the disease, such as in the control of calcium nephrolithiasis in enteric hyperoxaluria and hypomagnesuria.¹ Outside of these indications the effectiveness of magnesium is still debatable.

Furthermore, all magnesium-
based kidney stone prevention supplements are non-U.S. Food and Drug Administration approved, but most do follow guidelines for medical foods. As a result, there is minimal study of the formulations or preparations to verify their reported components, and there are no head-to-head trials comparing the effectiveness of these different formulations. Yet, the majority of supplements contain a combination of potassium and magnesium that are comparable to or cheaper than the cost of potassium citrate tablets (see Table).^7,8

Overall, magnesium supplementation to reduce kidney stone formation may have a role in certain disease states, such as enteric hyperoxaluria, but it remains of limited utility in the idiopathic stone former. It is difficult to augment this electrolyte in the average American diet, and although magnesium supplementation may result in increased urinary levels, its effect on stone prevention remains equivocal. This is yet another example of why there remains a need for further investigation of existing therapeutics, and the development of new therapeutics for secondary prevention of nephrolithiasis, as our arsenal remains limited. Hopefully, ongoing clinical trials will identify a clear leader in this space with the evaluation of multiple available agents.⁹