Reference
Taheri M, Jalali S, Borumandnia N, Tavasoli S, Basiri A, Taheri F. Effect of magnesium oxide or citrate supplements on metabolic risk factors in kidney stone formers with idiopathic hyperoxaluria: a randomized clinical trial. Magnes Res. 2024;37(1):12-21.
Study Objective
To assess the efficacy of magnesium oxide (MgO) or magnesium citrate (MgCit) on key urinary metabolites (such as oxalate, magnesium, citrate) and supersaturation indices (calcium oxalate [CaOx SS] and calcium phosphate [CaP SS]) in individuals who form calcium stones and have idiopathic hyperoxaluria
Key Takeaway
Magnesium citrate significantly reduces urinary oxalate levels and calcium oxalate supersaturation, offering a clinically effective and natural approach for preventing kidney stone formation, particularly in patients with normal urinary magnesium levels.
Design
Randomized, double-blind, placebo-controlled trial
Participants
Investigators recruited 90 participants from a nephrolithiasis prevention clinic; 76 participants completed the trial, for an 84% completion rate. Recruitment criteria included participants aged between 18 to 70 years. The mean age of each arm was 50.61±12.37 years (MgO), 48.69±10.64 years (MgCit), and 50.70±12.26 years (Placebo); P=0.466. Gender distribution for each arm was 26.1% female (MgO), 50% female (MgCit), and 74.1% female (Placebo).
These participants had a well-documented personal history of calcium stones and were diagnosed with idiopathic hyperoxaluria, with 24-hour urine oxalate levels between 40 and 80 mg.
Exclusion criteria included history of significant systemic diseases such as diabetes mellitus, hepatic failure, thyroid or parathyroid diseases, chronic kidney disease, chronic diarrhea, or immunological diseases. Participants were also excluded if they were pregnant or lactating, currently consuming any medications that interfered with calcium or oxalate metabolism, or had a urologic intervention within 20 days of evaluation.
Intervention
The active groups received either 120 mg of magnesium oxide or magnesium citrate 3 times daily with meals for 8 weeks, while the control group received a placebo of undisclosed ingredients at the same frequency and duration.
Study Parameters Assessed
Investigators assessed participants’ dietary intake through 24-hour food recalls before and after the intervention. This included tracking intake of high-oxalate foods, animal proteins, and other nutrients. They performed 24-hour urine analysis (24-U) at baseline and after 8 weeks, which included oxalate, magnesium, citrate, calcium, and urine pH as well as sodium, potassium, chloride, phosphorus, and uric acid.
Additionally, supersaturation indices included calcium oxalate and calcium phosphate calculated using Lithorisk© software. Investigators analyzed fasting blood samples for blood urea nitrogen, creatinine, calcium, and phosphorus.
Primary Outcome
The primary outcome the study was designed to assess was the change in 24-hour urine oxalate (24-U Ox) levels in patients with idiopathic hyperoxaluria who were treated with magnesium oxide, magnesium citrate, or placebo. Investigators measured this outcome to evaluate the effectiveness of these supplements in reducing oxalate levels, which are a key factor in kidney stone formation.
Key Findings
Magnesium citrate significantly reduced 24-U Ox levels by an average of 16.99 mg/day compared to placebo (P=0.011). In contrast, magnesium oxide also lowered oxalate levels by 8.13 mg/day, but this reduction was not statistically significant compared to the placebo group.
Additionally, both MgO and MgCit increased 24-hour urine magnesium levels (24-U Mg) without significant differences between the groups (P=0.628).
Regarding calcium oxalate supersaturation, MgCit resulted in a significant reduction compared to placebo (P=0.010), suggesting a potential benefit in reducing the risk of stone formation. MgO also demonstrated a reduction in CaOx SS, but it was not statistically significant.
Transparency
The study reported that there was no financial support provided for the research. Additionally, the authors disclosed that they had no conflicts of interest.
Practice Implications & Limitations
Nephrolithiasis, commonly known as kidney stone disease, is a prevalent condition characterized by the formation of stones, primarily composed of calcium oxalate, in the urinary tract. CaOx stones account for approximately 60% of all kidney stone cases, often driven by hyperoxaluria, a metabolic condition marked by elevated urinary oxalate excretion.1 A shared objective between conventional and natural medicine practitioners in managing nephrolithiasis is the reduction of hyperoxaluria.
Magnesium, a well-documented inhibitor of CaOx crystallization, offers a promising approach that has been explored in both clinical and experimental settings. This study sheds light on an often-asked question about whether the form of magnesium matters, at least within the context of supplementation in kidney stone prevention.2
Natural medicine practitioners often emphasize magnesium’s role in metabolic health, advocating its use for various conditions, including kidney stone prevention. MgCit’s dual action of enhancing urinary magnesium and citrate levels makes it particularly valuable, as citrate acts as a potent inhibitor of CaOx stone formation by complexing with calcium and reducing its availability to form stones.3
MgCit not only decreased 24-U Ox but also reduced the CaOx supersaturation index in this study. The CaOx SS index is a measure used to assess the risk of calcium oxalate kidney stone formation. Supersaturation occurs when the concentration of calcium and oxalate ions in the urine exceeds their solubility, leading to crystal formation, which is the first step in stone development. The CaOx SS quantifies this risk by determining how concentrated these ions are relative to their saturation threshold.4 Clinically, the CaOx SS directly reflects the likelihood of stone formation: the higher the index, the greater the risk of calcium oxalate crystals forming and growing into stones.5 It is measured by analyzing calcium, oxalate, pH, citrate, and other metabolites in urine samples. Specialized software, such as Lithorisk, assists in calculating the CaOx SS by integrating these multiple factors to provide an assessment of a patient's stone-forming risk.6
As one might expect, high levels of urinary calcium and oxalate increase the CaOx SS, while greater urine volume and higher levels of inhibitors, such as citrate, can help lower it. Management strategies often focus on reducing the CaOx SS by promoting hydration, adjusting dietary calcium and oxalate intake, and using therapeutic agents like citrate supplements, which reduce calcium availability by binding with calcium ions.
For patients with normal urinary magnesium levels, MgCit provided the most substantial reduction in oxalate excretion, supporting its targeted use in patients who may benefit from this specific supplementation.
Supersaturation occurs when the concentration of calcium and oxalate ions in the urine exceeds their solubility, leading to crystal formation, which is the first step in stone development.
Furthermore, MgCit’s ability to alkalinize urine adds an additional protective effect against stone formation, especially in individuals with a propensity for acidic urinary environments. Previous studies have shown that increasing urinary pH through magnesium supplementation can enhance citrate excretion, further lowering the risk of stone formation.7 This highlights MgCit’s multifunctional role in managing nephrolithiasis, making it a versatile tool.
While the findings of this study are promising, it has several limitations that must be considered. The intervention period was relatively short, spanning only 8 weeks, which may not fully capture the long-term impact of magnesium supplementation on kidney stone recurrence. Although investigators observed reductions in urinary oxalate and CaOx SS, it remains uncertain whether these changes translate into a sustained decrease in stone formation over longer periods. Alas, future studies with extended follow-up durations to evaluate the long-term clinical outcomes of magnesium supplementation would be helpful.
The study population, recruited from a tertiary stone-prevention clinic in Tehran, Iran, may not be fully representative of the broader patient demographics seen in other regions or clinical settings. Differences in dietary habits, comorbidities, and access to healthcare resources could influence the generalizability of the results. Moreover, to control for dietary intake, the study relied on 24-hour food recalls, which can be prone to reporting inaccuracies. These factors could impact the observed effects of magnesium supplementation on urinary metabolites, highlighting the need for more rigorous dietary assessment methods in future research.
Another limitation is the lack of direct comparison with other commonly used treatments for hyperoxaluria, such as potassium citrate. While MgCit was shown to be effective, its relative efficacy compared to these standard interventions remains unclear. Studies that directly compare MgCit with other agents would provide more comprehensive guidance for clinicians in selecting the most appropriate therapy for their patients.
Conflict of Interest Disclosure
The author is an employee of a company that sells dietary supplements that contain magnesium citrate.
