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