Summary: In an open-label, randomized crossover pharmacokinetic study of 15 healthy euthyroid adults, coadministration of 1 mg oral levothyroxine with magnesium aspartate significantly reduced thyroxine absorption, lowering the area under the curve by 12 percent (GMR 0.88, 95% CI 0.81 to 0.95, p = 0.002). Magnesium citrate produced a smaller, non-significant 7 percent reduction (GMR 0.93, 95% CI 0.86 to 1.01, p = 0.076).
PICO Summary
| Element | Detail |
|---|---|
| Population | 15 healthy, euthyroid adult volunteers; single-centre, open-label, randomized three-period crossover pharmacokinetic study (Switzerland). |
| Intervention | Single 1 mg oral levothyroxine tablet coadministered with either magnesium aspartate or magnesium citrate; thyroxine measured over 6 hours. Each participant received all three treatments (n = 15 per period), separated by a washout. |
| Comparison | The same 1 mg oral levothyroxine tablet given alone, without concurrent magnesium (within-subject reference, n = 15). |
| Outcome | Primary endpoint (thyroxine AUC): magnesium aspartate reduced AUC by 12% (GMR 0.88, 95% CI 0.81 to 0.95, p = 0.002); magnesium citrate reduced AUC by 7% non-significantly (GMR 0.93, 95% CI 0.86 to 1.01, p = 0.076). Secondary endpoints with aspartate: Cmax reduced by 7% and Tmax increased by 17% (both significant); changes were smaller with citrate. No ARR or NNT applies to this pharmacokinetic design. |
Expert Commentary
This is the first study to quantify the effect of magnesium on levothyroxine absorption, and the signal is consistent with what is already known for other divalent cations such as calcium and iron. The verdict is that magnesium aspartate measurably blunts levothyroxine absorption, with the prespecified primary endpoint met, whereas the citrate salt was associated with a smaller and statistically non-significant reduction. These findings are mechanistic and should be read as such; the work was a 6-hour pharmacokinetic study in 15 healthy euthyroid volunteers, not a clinical trial measuring thyrotropin control or symptoms in treated hypothyroid patients, so the durability and clinical magnitude of the interaction remain inferred rather than demonstrated. The principal limitation is the open-label design and the very small sample, which leaves the citrate estimate underpowered and its confidence interval crossing one. The single supratherapeutic 1 mg dose and a liquid magnesium formulation may also have softened the measured effect relative to everyday tablet dosing. No manufacturer sponsorship was reported, and the effect sizes are modest and biologically plausible rather than implausibly large. Can I use this with my patients? Yes, in a practical sense: a hypothyroid patient on levothyroxine, particularly one targeting a narrow thyrotropin range, should be advised to separate magnesium supplements from the morning dose, and citrate may be preferable to aspartate if the two must be taken together. Confirmatory outcome data in treated patients would be welcome.
References
Attinger MC, von Felten S, Rodrigues CL, Krützfeldt J, Risch L, Bonzon J. Single Center, Open-Label, Randomized Crossover Trial on Drug-Drug Interactions of Levothyroxine/Magnesium-Citrate and Levothyroxine/Magnesium-Aspartate in Healthy Subjects-The ThyroMag Trial. Clin Transl Sci. 2025;18(11):e70409. doi:10.1111/cts.70409