Work

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

Year: 2025

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: ABSTRACT Divalent cations such as calcium and ferrous sulfate interfere with the absorption of levothyroxine due to complexing. To our knowledge, the effects of magnesium on levothyroxine absorption have never been studied. The open‐label cross‐over pharmacokinetic study was conducted in 15 healthy, euthyroid adults. 1 mg of levothyroxine was administered in tablet form alone or co‐administered with either magnesium aspartate or magnesium citrate. Participants received all three treatments, separated by a washout period, but were randomly allocated 1:1:1 to one of three treatment sequences. We measured thyroxine (T4) over a 6‐h period after ingestion. The primary endpoint was the area under the curve (AUC) of thyroxine; secondary endpoints were C max and T max . Coadministration of magnesium aspartate significantly reduced thyroxine AUC by 12% (geometric mean ratio, GMR = 0.88, 95% CI 0.81–0.95, p = 0.002) and coadministration of magnesium citrate reduced thyroxine AUC non‐significantly by 7% compared with levothyroxine alone (GMR = 0.93, 95% CI 0.86–1.01, p = 0.076). C max was significantly reduced by 7% and T max was significantly increased by 17% when magnesium aspartate was co‐administered. The changes in C max and T max were smaller when magnesium citrate was co‐administered. In conclusion, magnesium reduces the absorption of levothyroxine. However, we found smaller effects compared to those already described for other divalent cations, possibly due to the liquid formulation. Hypothyroid patients should nonetheless take levothyroxine separated from magnesium‐containing formulations, especially if TSH levels are desired to be within a narrow range. If taken together, magnesium citrate may be a better option than magnesium aspartate.

Source: Clinical and Translational Science

DOI: 10.1111/cts.70409

Authors: Martin Christian Attinger, Stefanie von Felten, Claudia Lourenço Rodrigues, Jan Krützfeldt, Lorenz Risch, Jérôme Bonzon

Institutions: University of Zurich, University Hospital Zurich

Language: English

Topic: Thyroid Disorders and Treatments

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,630