Effect of calcium carbonate on the absorption of levothyroxine

JAMA. 2000 Jun 7;283(21):2822-5. doi: 10.1001/jama.283.21.2822.


Context: The effect of calcium carbonate on the absorption of levothyroxine has not been studied systematically. Such a potential drug interaction merits investigation because concurrent treatment with both drugs is common, particularly in postmenopausal women.

Objective: To investigate the potential interference of calcium carbonate in the absorption of levothyroxine.

Design: Prospective cohort study conducted from November 1998 to June 1999, supplemented with an in vitro study of thyroxine (T(4)) binding to calcium carbonate.

Setting: Veterans Affairs Medical Center in West Los Angeles, Calif.

Patients: Twenty patients (age range, 27-78 years; n=11 men) with hypothyroidism who were taking a stable long-term regimen of levothyroxine were included in the study. All patients had serum free T(4) and thyrotropin values in the normal range before beginning the study.

Intervention: Subjects were instructed to take 1200 mg/d of elemental calcium as calcium carbonate, ingested with their levothyroxine, for 3 months.

Main outcome measures: Levels of free T(4), total T(4), total triiodothyronine (T(3)), and thyrotropin, measured in all subjects at baseline (while taking levothyroxine alone), at 2 and 3 months (while taking calcium carbonate and levothyroxine), and 2 months after calcium carbonate discontinuation (while continuing to take levothyroxine).

Results: Mean free T(4) and total T(4) levels were significantly reduced during the calcium period and increased after calcium discontinuation. Mean free T(4) levels were 17 pmol/L (1.3 ng/dL) at baseline, 15 pmol/L (1.2 ng/dL) during the calcium period, and 18 pmol/L (1.4 ng/dL) after calcium discontinuation (overall P<.001); mean total T(4) levels were 118 nmol/L (9.2 microg/dL) at baseline, 111 nmol/L (8.6 microg/dL) during the calcium period, and 120 nmol/L (9.3 microg/dL) after calcium discontinuation (overall P=.03). Mean thyrotropin levels increased significantly, from 1.6 mIU/L at baseline to 2.7 mIU/L during the calcium period, and decreased to 1. 4 mIU/L after calcium discontinuation (P=.008). Twenty percent of patients had serum thyrotropin levels higher than the normal range during the calcium period; the highest observed level was 7.8 mIU/L. Mean T(3) levels did not change during the calcium period. The in vitro study of T(4) binding to calcium showed that adsorption of T(4) to calcium carbonate occurs at acidic pH levels.

Conclusions: This study of 20 patients receiving long-term levothyroxine replacement therapy indicates that calcium carbonate reduces T(4) absorption and increases serum thyrotropin levels. Levothyroxine adsorbs to calcium carbonate in an acidic environment, which may reduce its bioavailability. JAMA. 2000;283:2822-2825

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Adult
  • Aged
  • Biological Availability
  • Calcium Carbonate / metabolism
  • Calcium Carbonate / pharmacology*
  • Calcium Carbonate / therapeutic use
  • Cohort Studies
  • Drug Interactions
  • Female
  • Humans
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Thyrotropin / metabolism
  • Thyroxine / metabolism
  • Thyroxine / pharmacokinetics*
  • Thyroxine / therapeutic use
  • Triiodothyronine / metabolism


  • Triiodothyronine
  • Thyrotropin
  • Calcium Carbonate
  • Thyroxine