Thyroid Hormone absorption interference

Jacob Schor ND FABNO

September 9, 2008

Coffee has been added to the list of things that interfere with absorption of thyroid hormone.  The list of things that you shouldn’t take along with thyroid hormone keeps growing. Most simply hinder absorption of the drug from the digestive tract and effectively reduce the dose that gets into your blood.  This isn’t a big problem is you only eat these foods rarely; if for one day you don’t absorb all of your thyroid dose, it’s not a big deal.  If you eat the same foods every single day, it’s also not a big deal because you’ll adjust the amount of medicine you take to a slightly higher dose and compensate.  The problem shows up with food or other medications that people will start to take regularly.  This can throw of your dose requirements.

Take coffee.  This may be a problem for many people with hypothyroid function who are taking replacement hormone.  If these people are under treated they feel really tired.  If they are also vitamin B-12 deficient, the feel really, really tired. 

Tired people drink coffee.  According to a paper published this past March, coffee decreased the amount of thyroid hormone absorption by about a third.  Instead of tired, these people will start to feel exhausted.   So, they drink more coffee and they absorb even less of their hormone dose.  It’s a vicious cycle.  The trick is to take thyroid hormone first thing in the morning on an empty stomach, at least 30 minutes before eating anything. 

Coffee isn’t the first thing discovered to interfere with thyroid hormone.  Back in 1992 both aluminum hydroxide antacids and the iron supplement ferrous sulfate were reported to interfere.  In 2000 a report in JAMA added calcium carbonate to the list.    Soy protein shakes were added in 2001. The drug Raloxifene was added in 2003.   Then chromium picolinate in 2007.   And now, coffee.

Some patients just lie and tell their doctors that they took their medicine when they didn’t.   But not our patients.  There are some foods, namely cabbage that are well known to decrease thyroid hormone production and cause goiters if eaten in large enough quantities, but that’s not what I’m writing about here.

Thus the general direction given to all patients taking supplemental thyroid hormone to always take it alone without food or other medication.  You just don’t know what’s going to mess things up.

When a patient who is taking thyroid hormone does well initially and then it seems the drug stops working, the first thing to rule out is interference from something else they are taking.

A 2007 paper tells us that taking thyroid hormone at bedtime works much better than taking it in the morning.  For some reason the hormone is better absorbed at night and reaches greater blood concentrations than when taken in the morning.   [I confess that I just read this for the first time and haven't tried it with anyone as of this writing. ]

REFERENCES:

Thyroid. 2008 Mar;18(3):293-301.Click here to read Links

    Altered intestinal absorption of L-thyroxine caused by coffee.

    Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, Saraceno G, Trimarchi F.

    Sezione di Endocrinologia del Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Università di Messina, Messina, Italy. s.benvenga@me.nettuno.it

    OBJECTIVE: To report eight case histories, and in vivo and in vitro studies showing coffee's potential to impair thyroxine (T4) intestinal absorption. DESIGN: Of eight women with inappropriately high or nonsuppressed thyroid-stimulating hormone (TSH) when T4 was swallowed with coffee/espresso, six consented to the evaluation of their T4 intestinal absorption. This in vivo test was also administered to nine volunteers. In three separate tests, two 100 microg T4 tablets were swallowed with coffee, water, or water followed, 60 minutes later, by coffee. Serum T4 was assayed over the 4-hour period of the test. Two patients and two volunteers also agreed on having tested the intestinal absorption of T4 swallowed with solubilized dietary fibers. In the in vitro studies, classical recovery tests on known concentrations of T4 were performed in the presence of saline, coffee, or known T4 sequestrants (dietary fibers, aluminium hydroxide, and sucralfate). MAIN OUTCOME: For the in vivo test, average and peak incremental rise of serum T4 (AIRST4 and PIRST4), time of maximal incremental rise of serum T4 (TMIRST4), and area under the curve (AUC) were determined. In patients and volunteers, the four outcome measures were similar in the water and water + coffee tests. In patients and volunteers, compared to water, coffee lowered AIRST4 (by 36% and 29%), PIRST4 (by 30% and 19%), and AUC (by 36% and 27%) and delayed TMIRST4 (by 38 and 43 minutes); bran was a superior interferer. In the in vitro studies, coffee was weaker than known T4 sequestrants. CONCLUSION: Coffee should be added to the list of interferers of T4 intestinal absorption, and T4 to the list of compounds whose absorption is affected by coffee.

 

Arch Intern Med. 1992 Jan;152(1):183-4.Links

    Evidence for interference with the intestinal absorption of levothyroxine sodium by aluminum hydroxide.

    Sperber AD, Liel Y.

    Institute of Gastroenterology, Soroka, Medical Center, Beer-Sheva, Israel.

    A patient with hypothyroidism who was euthyroid on a fixed-dosage, long-term maintenance regimen of levothyroxine sodium developed persistently elevated serum thyrotropin levels while receiving an aluminum hydroxide-containing antacid. The thyrotropin levels returned to normal shortly after cessation of the antacid therapy. These observations indicate that aluminum hydroxide may interfere with the bioavailability of thyroxine. The thyroid function of patients who are receiving replacement or suppressive thyroxine therapy should be monitored following the commencement of concurrent treatment with medications containing aluminum hydroxide.

Ann Intern Med. 1992 Dec 15;117(12):1010-3.Links

    Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism.

    Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC.

    Department of Medicine, Faculty of Medicine, University of Calgary, Alberta, Canada.

    OBJECTIVE: To determine whether simultaneous ingestion of ferrous sulfate and thyroxine reduces the efficacy of thyroid hormone in patients with primary hypothyroidism. DESIGN: Uncontrolled clinical trial. SETTING: Outpatient research clinic of a tertiary care center. PATIENTS: Fourteen patients with established primary hypothyroidism on stable thyroxine replacement. INTERVENTION: All patients were instructed to ingest simultaneously, a 300-mg ferrous sulfate tablet and their usual thyroxine dose every day for 12 weeks. RESULTS: After 12 weeks of ferrous sulfate ingestion with thyroxine, the mean level of serum thyrotropin (thyroid stimulating hormone, TSH) rose from 1.6 +/- 0.4 to 5.4 +/- 2.8 mU/L (P < 0.01), but the free thyroxine index did not change significantly. Subjective evaluation using a clinical score showed that nine patients had an increase in symptoms and signs of hypothyroidism; the mean score for the 14 patients changed from 0 to 1.3 +/- 0.4 (P = 0.011). When iron and thyroxine were mixed together in vitro, a poorly soluble purple complex appeared that indicated the binding of iron to thyroxine. CONCLUSIONS: Simultaneous ingestion of ferrous sulfate and thyroxine causes a variable reduction in thyroxine efficacy that is clinically significant in some patients. The interaction is probably caused by the binding of iron to thyroxine.

JAMA. 2000 Jun 7;283(21):2822-5.Click here to read Links

    Effect of calcium carbonate on the absorption of levothyroxine.

    Singh N, Singh PN, Hershman JM.

    Division of Endocrinology and Metabolism, Endocrinology 111D, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA 90073. nsingh@ucla.edu

    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

Endocr Pract. 2001 May-Jun;7(3):193-4.Click here to read Links

    Use of soy protein supplement and resultant need for increased dose of levothyroxine.

    Bell DS, Ovalle F.

    Division of Endocrinology and Metabolism, The University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama, USA.

    OBJECTIVE: To report a case of difficulty in achieving suppressive serum levels of thyroid hormone because of malabsorption of exogenous levothyroxine attributable to daily ingestion in close temporal relationship to the intake of a soy protein-containing food supplement. METHODS: We present the relevant history and laboratory data of the current case and provide supportive documentation from the literature. RESULTS: A 45-year-old woman who had hypothyroidism after a near-total thyroidectomy and radioactive iodine ablative therapy for papillary carcinoma of the thyroid required unusually high oral doses of levothyroxine to achieve suppressive serum levels of free thyroxine (T(4)) and thyrotropin (thyroid-stimulating hormone or TSH). She had routinely been taking a "soy cocktail" protein supplement immediately after her levothyroxine. Temporal separation of the intake of the soy protein cocktail from the administration of the levothyroxine resulted in attainment of suppressive serum levels of free T(4) and TSH with use of lower doses of levothyroxine. CONCLUSION: Administration of levothyroxine concurrently with a soy protein dietary supplement results in decreased absorption of levothyroxine and the need for higher oral doses of levothyroxine to attain therapeutic serum thyroid hormone levels.

Arch Intern Med. 2003 Jun 9;163(11):1367-70.Click here to read Links

    Raloxifene causing malabsorption of levothyroxine.

    Siraj ES, Gupta MK, Reddy SS.

    Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

    To our knowledge, raloxifene hydrochloride, a selective estrogen receptor modulator, has never been reported to interfere with absorption of levothyroxine. We describe a 79-year-old woman with chronic, treated primary hypothyroidism, presenting with increasing levothyroxine requirement while taking raloxifene at the same time as levothyroxine. For two 6- to 8-week periods, we separated the ingestion of raloxifene and levothyroxine by about 12 hours. In addition, we tested the absorption of 1.0 mg of levothyroxine sodium with and without the coadministration of 60 mg of raloxifene hydrochloride on 2 separate occasions by collecting serial blood samples for 6 hours. Hypothyroidism occurred in a reproducible fashion whenever levothyroxine and raloxifene were administered together and improved whenever they were taken separately. Combined administration of levothyroxine and raloxifene resulted in lower levels of serum thyroxine compared with administration of levothyroxine alone. By a yet unknown mechanism, raloxifene caused malabsorption of levothyroxine in our patient when coadministered.

Thyroid. 2007 Aug;17(8):763-5.Click here to read Links

    New medications which decrease levothyroxine absorption.

    John-Kalarickal J, Pearlman G, Carlson HE.

    Endocrinology Division, Department of Medicine, Stony Brook University School of Medicine, Stony Brook, New York 11794-8154, USA.

    OBJECTIVE: Medications may sometimes interfere with the intestinal absorption of levothyroxine, primarily by forming an insoluble complex with the thyroid hormone in the intestinal lumen. The goal of this study was to examine the acute effects of three previously unstudied medications on levothyroxine absorption. DESIGN: We studied the effects of three medications on thyroxine absorption in seven normal volunteers. On each study day, the subjects ingested 1 mg levothyroxine sodium, either taken separately or co-administered with sevelamer hydrochloride (Renagel, a phosphate-binding medication used in the treatment of hyperphosphatemia), chromium picolinate (an over-the-counter nutritional supplement), or ezetimibe (Zetia, a drug used in the treatment of hypercholesterolemia). Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. MAIN OUTCOME: Sevelamer hydrochloride and chromium picolinate each significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve, while ezetimibe had no effect. CONCLUSION: Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours.

Presse Med. 2007 Oct;36(10 Pt 1):1390-4. Epub 2007 Apr 18.Click here to read Links

    [L-thyroxine pseudomalabsorption: a factitious disease]

    [Article in French]

    Molines L, Fromont I, Morlet-Barla N, Nogueira JP, Valéro R, Vialettes B.

    Service de nutrition, maladies métaboliques et endocrinologie, Hôpital La Timone, Marseille. lmolines77@yahoo.fr

    INTRODUCTION: Thyroxine supplementation of patients with hypothyroidism is usually simple. A few patients, however, continue to present elevated TSH levels despite large doses of L-thyroxine. CASE: We report the case of a 71-year-old women who had had a thyroidectomy 10 years earlier and had since been hospitalized repeatedly for profound hypothyroidism. Despite her consistent claims of good adherence to her treatment regimen, we considered the diagnosis of L-thyroxine pseudomalabsorption and confirmed it by thyroid hormone absorption tests. DISCUSSION: L-thyroxine pseudomalabsorption due to concealed poor treatment adherence should be considered after ruling out drug or dietary interference and true organic malabsorption. Diagnosis of this factitious disease can be confirmed by L-thyroxine absorption tests.

Clin Endocrinol (Oxf). 2007 Jan;66(1):43-8.Click here to read Links

    Effects of evening vs morning thyroxine ingestion on serum thyroid hormone profiles in hypothyroid patients.

    Bolk N, Visser TJ, Kalsbeek A, van Domburg RT, Berghout A.

    Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.

    OBJECTIVE: Standard drug information resources recommend that l-thyroxine be taken half an hour before breakfast on an empty stomach, to prevent interference of its intestinal uptake by food or medication. We observed cases in which TSH levels improved markedly after changing the administration time of l-thyroxine to the late evening. We therefore conducted a pilot-study to investigate whether l-thyroxine administration at bedtime improves TSH and thyroid hormones, and whether the circadian rhythm of TSH remains intact. DESIGN Patients were studied on two occasions: on a stable regimen of morning thyroxine administration and two months after switching to night-time thyroxine using the same dose. On each occasion patients were admitted for 24 h and serial blood samples were obtained. PATIENTS: We investigated 12 women treated with l-thyroxine because of primary hypothyroidism, who used no medication known to interfere with l-thyroxine uptake. MEASUREMENTS: Patients were admitted to hospital and blood samples were obtained at hourly intervals for 24 h via an indwelling catheter. Following this first hospital admission, all women were asked to switch the administration time from morning to bedtime or vice versa. After 2 months they were readmitted for a 24-h period of hourly blood sampling. Blood samples were analysed for serum TSH (immunometric assay), FT4 and T3 (competitive immunoassay), T4 and rT3 (radioimmunoassay), serum TBG (immunometric assay) and total protein and albumin (colourimetric methods). RESULTS: A significant difference in TSH and thyroid hormones was found after switching to bedtime administration of l-thyroxine. Twenty-four-hour average serum values amounted to (mean +/- SD, morning vs bedtime ingestion): TSH, 5.1 +/- 0.9 vs 1.2 +/- 0.3 mU/l (P < 0.01); FT4, 16.7 +/- 1.0 vs 19.3 +/- 0.7 pmol/l (P < 0.01); T3, 1.5 +/- 0.05 vs 1.6 +/- 0.1 nmol/l (P < 0.01). There was no significant change in T4, rT3, albumin and TBG serum levels, nor in the T3/rT3 ratio. The relative amplitude and time of the nocturnal TSH surge remained intact. CONCLUSIONS: l-thyroxine taken at bedtime by patients with primary hypothyroidism is associated with higher thyroid hormone concentrations and lower TSH concentrations compared to the same l-thyroxine dose taken in the morning. At the same time, the circadian TSH rhythm stays intact. Our findings are best explained by a better gastrointestinal uptake of l-thyroxine during the night.