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Magnesium Supplementation and Tachyarrhythmias: A Nonrandomized Clinical Trial.

  • 2026-02-01
  • JAMA internal medicine 186(2)
    • Robert Goulden
    • Michal Abrahamowicz
    • Erin Strumpf
    • Robyn Tamblyn

Study Design

Type
Clinical Trial
Sample size
n = 478
Population
ICU patients undergoing serum magnesium testing in 93 ICUs across the US and Europe
Methods
Nonrandomized clinical trial using fuzzy regression discontinuity design, comparing individuals just either side of the eligibility cutoff for magnesium supplementation across a range of treatment cutoffs from 1.6 mg/dL to 2.0 mg/dL
  • Large Human Trial
  • Rigorous Journal

Importance

Magnesium supplementation is regularly given to acutely ill patients with serum levels below the standard reference range, primarily for the prevention of tachyarrhythmias, such as atrial fibrillation. The evidence for this practice and the specific treatment thresholds used is limited. Conventional observational studies of this question are at risk of confounding by indication and other biases.

Objective

To determine whether giving magnesium supplementation to patients with hypomagnesemia, as defined by a given institution's usual treatment cutoff, reduces adverse clinical outcome using a quasi-experimental study design that plausibly allows for causal inference.

Design, setting, and participants

This nonrandomized clinical trial of intensive care unit (ICU) patients undergoing serum magnesium testing was conducted in 93 ICUs across the US and Europe between 2003 and 2022. A fuzzy regression discontinuity design was used, in which individuals just either side of the eligibility cutoff for magnesium supplementation were compared with regard to the study outcomes. This comparison was performed across a range of treatment cutoffs in current use, ranging from 1.6 mg/dL to 2.0 mg/dL. Data were analyzed from August to October 2025.

Exposures

Magnesium supplementation.

Main outcomes and measures

The primary outcome was ventricular or supraventricular tachyarrhythmia in the 24 hours after magnesium testing. Secondary outcomes were the occurrence of hypotension or death.

Results

A total of 478 901 twenty-four-hour treatment windows from 171 727 ICU admissions were included in the study. A total of 72 767 admitted patients (42.4%) were female, 98 960 (57.6%) were male, and the mean (SD) age of the cohort was 63 (16) years. There was no evidence of an effect of magnesium supplementation on the occurrence of tachyarrhythmia, with a risk difference of 0.1% (95% CI, -4.2 to 6.9). This was true across all the cutoff levels evaluated. There was similarly no association with the occurrence of hypotension (risk difference, 1.2%; 95% CI, -0.9 to 17.7) or death (risk difference, 1.4%; 95% CI, -0.6 to 5.3).

Conclusions and relevance

In this nonrandomized clinical trial, routine supplementation of magnesium with currently used doses and treatment thresholds was not associated with beneficial effects for individuals with serum magnesium values close to those cutoffs.

Research Insights

  • Magnesium→Reduced Hypotension

    There was similarly no association with the occurrence of hypotension (risk difference, 1.2%; 95% CI, -0.9 to 17.7).

    Effect
    Neutral
    Effect size
    Small
  • Magnesium→Reduced Mortality

    There was similarly no association with the occurrence of ... death (risk difference, 1.4%; 95% CI, -0.6 to 5.3).

    Effect
    Neutral
    Effect size
    Small
  • Magnesium→Reduced Tachyarrhythmia

    There was no evidence of an effect of magnesium supplementation on the occurrence of tachyarrhythmia, with a risk difference of 0.1% (95% CI, -4.2 to 6.9).

    Effect
    Neutral
    Effect size
    Small

Adverse Events Reported

  • Magnesium→death

    There was similarly no association with the occurrence of hypotension (risk difference, 1.2%; 95% CI, -0.9 to 17.7) or death (risk difference, 1.4%; 95% CI, -0.6 to 5.3).

    Finding
    No significant difference
    Severity
    Serious adverse event
    Magnitude
    risk difference, 1.4%; 95% CI, -0.6 to 5.3
    Significant
    No
  • Magnesium→hypotension

    There was similarly no association with the occurrence of hypotension (risk difference, 1.2%; 95% CI, -0.9 to 17.7) or death (risk difference, 1.4%; 95% CI, -0.6 to 5.3).

    Finding
    No significant difference
    Magnitude
    risk difference, 1.2%; 95% CI, -0.9 to 17.7
    Significant
    No
  • Magnesium→tachyarrhythmia

    There was no evidence of an effect of magnesium supplementation on the occurrence of tachyarrhythmia, with a risk difference of 0.1% (95% CI, -4.2 to 6.9).

    Finding
    No significant difference
    Severity
    Serious adverse event
    Magnitude
    risk difference of 0.1% (95% CI, -4.2 to 6.9)
    Significant
    No
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