EBM Consult

How does aluminum hydroxide inhibits the absorption of levothyroxine (T4; Levothroid, Levoxyl, Synthroid, and Unithroid)?


  • Given the availability of aluminum hydroxide in common over-the-counter (OTC) supplements, their daily or intermittent administration in patients with hypothyroidism on levothyroxine (synthetic T4) is plausible.
  • A numbers of factors (such as food, H2 receptor antagonists, proton pump inhibitors, etc) as well as aluminum hydroxide itself are known to increase the gastric pH (ranging from 1 to 6).
  • Levothyroxine has a carboxyl group (R-COOH) as part of its structure which can ionize, or release its H+ ion, and become negatively charged (R-COO-) when the gastric pH exceeds its pKa of 1.8 to 2.4.
  • The negatively charged carboxyl groups (R-COO-) can then interact with the positively charged aluminum ions (Al3+) resulting in "chelation".    
  • The coadministration of aluminum hydroxide and levothyroxine can result in a significant loss of control of thyroid hormone concentrations in the body.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed: August 2015


  • The oral antacid, aluminum hydroxide, is commonly used for the treatment of acid indigestion, gastroesophageal reflux disease and even to reduce phosphate absorptions in patients with hyperphosphatemia secondary to chronic kidney disease.  Due to its presence as an ingredient in several over-the-counter (OTC) products, such as Maalox and Mylanta, it is plausible that it could be used by patients without the consultation or knowledge of a healthcare provider.  While this may not be a problem if that patient is on no other medications, it could result in the loss of thyroid control in hypothyroid patients taking levothyroxine (synthetic T4) therapy.1-3  This would be especially true in patients who take aluminum containing products within 2-4 hours of taking their levothyroxine.(1,3)  In fact, pharmacokinetic drug interaction studies have shown that thyroid stimulating hormone (TSH; thyrotropin) concentrations increase from an average of 2.62 mU/L up to 7.19 mU/L (normal range or control 0.5 - 5.0 mU/L).(3)  This increase would suggest a significant loss of thyroid control.  It appears that the interaction comes from a reduction in the absorption of levothyroxine.  Most clinicians will say that aluminum or other di- or tri-valent cations will "chelate" with levothyroxine to prevent absorption, but what does that actually mean?

    What is the exact mechanism by which aluminum hydroxide actually decreases the absorption of levothyroxine?

    • A basic evaluation of the chemical structure of levothyroxine reveals that each levothyroxine molecule has one carboxyl group (R-COOH) as part of its structure.(1,4)  The important thing to note about this carboxyl group as it relates to an interaction with aluminum is its ionization state (i.e., whether it is charged or uncharged).  The carboxyl group becomes negatively charged when it releases its hydrogen (H+) ion. 
    • This process is determined by its pKa, which is the pH where there the medication is present equally in its ionized and nonionized states.  The pKa for carboxyl groups is approximately 1.8 to 2.4.5  Therefore, a pH above this pKa would result in a greater percentage of the carboxyl groups on levothyroxine being ionized (or in their negatively charged state). 
    • Depending on other medications being taken by the patient and the type of food ingested, the pH of the stomach can easily range from 1 to 6; thus, it is likely that the pKa of the carboxyl group will be exceeded.  However, even if the patient only takes the aluminum hydroxide along with the levothyroxine on an empty stomach, the aluminum hydroxide itself can interact with hydrochloric acid from the stomach to form aluminum chloride and water thereby increasing the gastric pH. 
    • Therefore, the magnitude of change in gastric pH (whether it is from aluminum hydroxide itself or from the combination of aluminum hydroxide and other medications) will influence the amount of ionized carboxyl groups found on levothyroxine.  Once this ionization has started to occur, the exposed and negatively charged group on levothyroxine can then bind to the positively charged aluminum (Al3+) ion that was present in the medication or supplement administered. 
    • This final reaction is what most clinicians refer to when they say that aluminum or a cation (positively charged molecule) can "chelate" levothyroxine.  The degree or significance of this interaction is, however, dependent on the time of their exposure to one another and the pH of the environment at the time. 
    • The current product package inserts for levothyroxine products recommend separating the dose of aluminum containing products from levothyroxine by at least 4 hours.(1)  This will provide sufficient time for the absorption of levothyroxine without the presence or interaction of aluminum.  This drug interaction with a common OTC medication highlights the importance for doing a thorough medication use evaluation.


    1. Levothyroxine (Synthroid) product package insert.  Abbott Laboratories.  North Chicago, IL.  March 2008.
    2. Sperber AD, Liel Y.  Evidence for interference with the intestinal absorption of levothyroxine sodium by aluminum hydroxide.  Arch Intern Med  1992;152:183-4.
    3. Liel Y, Sperber AD, Shany S.  Nonspecific intestinal absorption of levothyroxine by aluminum hydroxide.  Am J Med  1994;97:363-5.
    4. Zand R, Palmer G.  Ultraviolet, visible, circular dichroism, and electron paramagnetic resonance spectra of the copper (II) complexes of thyroxine and thyroxine analogs.  Biochemistry  1967;6:999-1007.
    5. Leiberman M, Marks AD, eds.  Mark's Basic Medical Biochemistry A Clinical Approach.  3rd Ed.  Philadelphia, PA: Lippincott Williams & Wilkins; 2009:75-91.


  • Synthroid, Levothyroxine, T4, Thyroid hormone, Levoxyl, Levothroid, Unithroid, Hypothyroidism, Aluminum hydroxide, Aluminum Levothyroxine Interaction