The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration
Open accessAbstract
CONTEXT: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action. OBJECTIVE: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels. DESIGN: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T(4), and total T(3) during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens. SETTING: The study was conducted in an academic medical center. PARTICIPANTS: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer. RESULTS: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 +/- 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 +/- 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 +/- 2.66 mIU/liter). CONCLUSION: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In a study which compared three timing regimens in 65 patients with primary hypothyroidism, a with-breakfast dosing resulted in the highest and most variable TSH levels, while a regimen of LT4 being administered an hour before breakfast was associated with the lowest and least variable TSH; the bedtime LT4 regimen produced values and variability that was in-between the other two dosing regimens (4”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [41]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Two recent cross-over studies had different findings with the lowest serum TSH values being seen either 1 hour before breakfast or at bedtime (128,129).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [128]
The cited source says what the claim attributes to it.
In the citing paper
“The mean TSH values seen with these different conditions were 1.06, 2.93, and 2.19 mIU/L respectively (128).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [128]
The cited source says what the claim attributes to it.
In the citing paper
“Four studies (121,126,128,129), out of the six studies examining this issue (121,128-131), have shown that the timing of LT4 administration influences the serum TSH values of hypothyroid patients receiving treatment.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [128]
In the citing paper
“Coingestion with breakfast or coffee can reduce and delay absorption (21, 22).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [21]
In the citing paper
“Bach-Huynh et al. three-period crossover study of 65 LT4-treated stable hypothyroid patients found that non-fasting LT4 administration was associated with higher and more variable serum TSH concentrations [ 33 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418
Outcomes of Patients with Differentiated Thyroid Carcinoma Following Initial Therapy
Jonklaas, J., Sarlis, N. J., Litofsky, D. R., Ain, K. B., Bigos, S. T., Brierley, J. D., Cooper, D. S., Haugen, B. R., Ladenson, P. W., Magner, J. A., et al. (2006) · Thyroid · doi:10.1089/thy.2006.16.1229 · Cited by 693
Andersen, S., Pedersen, K. M., Bruun, N. H., & Laurberg, P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.3.8165 · Cited by 686
Fish, L. H., Schwartz, H. L., Cavanaugh, J., Steffes, M. W., Bantle, J. P., & Oppenheimer, J. H. (1987) · New England Journal of Medicine · doi:10.1056/nejm198703263161302 · Cited by 353
Thyroxine in Goiter, Helicobacter pylori Infection, and Chronic Gastritis
Centanni, M., Gargano, L., Canettieri, G., Viceconti, N., Franchi, A., Fave, G. D., & Annibale, B. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa043903 · Cited by 329
Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism
Campbell, N. R. C., Hasinoff, B. B., Stalts, H., Rao, B., & Wong, N. C. W. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-12-1010 · Cited by 231
Effect of calcium carbonate on the absorption of levothyroxine
Singh, N. (2000) · JAMA · doi:10.1001/jama.283.21.2822 · Cited by 219
CARR, D., MCLEOD, D. T., PARRY, G., & THORNES, H. M. (1988) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1988.tb01219.x · Cited by 210
Altered intestinal absorption of L-thyroxine caused by coffee
Benvenga, S., Bartolone, L., Pappalardo, M. A., Russo, A., Lapa, D., Giorgianni, G., Saraceno, G., & Trimarchi, F. (2008) · Thyroid · doi:10.1089/thy.2007.0222 · Cited by 191 · cited 2×
“Additional factors affecting the absorption of LT4 are food (1–4, 22, 23), including high-fiber diets (24), soy (25), and beverages (26).”
BackgroundDelayed Intestinal Absorption of Levothyroxine
BENVENGA, S., BARTOLONE, L., SQUADRITO, S., GIUDICE, F. L., & TRIMARCHI, F. (1995) · Thyroid · doi:10.1089/thy.1995.5.249 · Cited by 156
Research works printed but not linked: 2
- Lamson, 2004, Quantitation of a substantial reduction in levothyroxine (T4) absorption by food, Thyroid, 14, 876
- Elliott, 2001, Effect of levothyroxine administration time on serum TSH in elderly patients., Ann Pharmacother, 35, 529, 10.1345/aph.10286 · DOI · Paper page
Cited by
Sorted by citations
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
“Two recent cross-over studies had different findings with the lowest serum TSH values being seen either 1 hour before breakfast or at bedtime (128,129).”
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber, K. A. (2012) · Endocrine Practice · doi:10.4158/ep12280.gl · Cited by 1,567
“Another study showed that taking it 60 minutes before breakfast on an empty stomach was better than taking it within 2 hours of the last meal of the day, which in turn was better than taking it within 20 minutes of breakfast (166).”
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber for the American Association, K. A. (2012) · Thyroid · doi:10.1089/thy.2012.0205 · Cited by 1,053
“Another study showed that taking it 60 minutes before breakfast on an empty stomach was better than taking it within 2 hours of the last meal of the day, which in turn was better than taking it within 20 minutes of breakfast (166).”
2013 ETA Guideline: Management of Subclinical Hypothyroidism
Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013) · European Thyroid Journal · doi:10.1159/000356507 · Cited by 877
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259
“of the difference in receiving L-T4 in either a fasting state, at bedtime, or with breakfast (266).”
BackgroundHypothyroidism: etiology, diagnosis, and management
Almandoz, J. P., & Gharib, H. (2012) · Medical Clinics of North America · doi:10.1016/j.mcna.2012.01.005 · Cited by 216
Treatment for primary hypothyroidism: current approaches and future possibilities
Vaidya, B., Chakera, A. J., & Pearce, S. H. S. (2011) · Drug Design Development and Therapy · doi:10.2147/dddt.s12894 · Cited by 204
“In contrast, a randomized crossover trial in the US compared taking levothyroxine in the fasting state, with breakfast, or at bedtime in 65 patients with primary hypothyroidism and thyroid cancer, and found that TSH levels were significantly lower and less variable when levothyroxine was taken in the fasting state tha…”
Gastrointestinal malabsorption of thyroxine
Virili, C., Antonelli, A., Santaguida, M. G., Benvenga, S., & Centanni, M. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00168 · Cited by 164
Clinical practice guidelines for the management of hypothyroidism
Brenta, G., Vaisman, M., Sgarbi, J. A., Bergoglio, L., de Andrada, N. C., Bravo, P. P., Orlandi, A. M., & Graf, H. (2013) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302013000400003 · Cited by 163
“This finding favors ingestion of L-T4 during morning fast, delaying food ingestion for 30 minutes (187) (A).”
BackgroundFactors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
Skelin, M., Lucijanić, T., Amidžić Klarić, D., Rešić, A., Bakula, M., Liberati-Čizmek, A.-M., Gharib, H., & Rahelić, D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.01.005 · Cited by 133
Effects of Evening vs Morning Levothyroxine Intake: A Randomized Double-blind Crossover Trial
Bolk, N. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.436 · Cited by 128
Hashimoto’s Thyroiditis and Autoimmune Gastritis
Cellini, M., Santaguida, M. G., Virili, C., Capriello, S., Brusca, N., Gargano, L., & Centanni, M. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00092 · Cited by 120
Hypothyroidism and Thyroiditis
Brent, G. A., & Davies, T. F. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00013-4 · Cited by 115
Atypical celiac disease as cause of increased need for thyroxine: a systematic study
Virili, C., Bassotti, G., Santaguida, M. G., Iuorio, R., Del Duca, S. C., Mercuri, V., Picarelli, A., Gargiulo, P., Gargano, L., & Centanni, M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1851 · Cited by 114
“3 g/kg body weight/day) under fasting conditions, waiting at least 1 h before eating, according to recent evidence (3, 6, 21).”
MethodDiagnosis and management of treatment-refractory hypothyroidism: an expert consensus report
Centanni, M., Benvenga, S., & Sachmechi, I. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0706-y · Cited by 113
“Review the thyroxine ingestion history The most efficient way to take levothyroxine—and the most reproducible—is to ingest the tablets on an empty stomach and avoid other medications or food for 30–60 min (preferably 60) thereafter [4, 5, 48].”
BackgroundThyroid hormone therapy for hypothyroidism
Biondi, B., & Cooper, D. S. (2019) · Endocrine · doi:10.1007/s12020-019-02023-7 · Cited by 112
Vita, R., Saraceno, G., Trimarchi, F., & Benvenga, S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2684 · Cited by 99
“The best timing of LT4 ingestion is in the morning, at least 1 hour before breakfast (6, 10, 11).”
BackgroundLevothyroxine Dose Adjustment to Optimise Therapy Throughout a Patient’s Lifetime
Duntas, L. H., & Jonklaas, J. (2019) · Advances in Therapy · doi:10.1007/s12325-019-01078-2 · Cited by 99
The administration of l -thyroxine as soft gel capsule or liquid solution
Vita, R., Fallahi, P., Antonelli, A., & Benvenga, S. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.918101 · Cited by 93
“Indeed, the maximum absorption occurs after the overnight fasting in the morning, whereas the lowest occurs when L-T4 is taken together with breakfast [19,22].”
BackgroundVita, R., Saraceno, G., Trimarchi, F., & Benvenga, S. (2013) · Endocrine · doi:10.1007/s12020-012-9772-2 · Cited by 91
Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age
Devdhar, M., Drooger, R., Pehlivanova, M., Singh, G., & Jonklaas, J. (2011) · Thyroid · doi:10.1089/thy.2011.0029 · Cited by 90
Self-citationOptimal thyroid hormone replacement
Jonklaas, J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab031 · Cited by 89
Levothyroxine interactions with food and dietary supplements – a systematic review
Wiesner, A., Gajewska, D., & Paśko, P. (2021) · Pharmaceuticals · doi:10.3390/ph14030206 · Cited by 85
“Similar results were obtained in many other studies [26–30].”
ResultCappelli, C., Pirola, I., Daffini, L., Formenti, A., Iacobello, C., Cristiano, A., Gandossi, E., Agabiti Rosei, E., & Castellano, M. (2016) · Thyroid · doi:10.1089/thy.2015.0422 · Cited by 80
“(9) observed that treatment with a soft gel preparation of LT4 (Tiche capsules, IBSA Switzer-land) is not associated with reduced absorption of the drug by coffee (14).”
Cohen, B. M., Sommer, B. R., & Vuckovic, A. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17080949 · Cited by 79
When thyroid hormone replacement is ineffective?
Benvenga, S. (2013) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000003 · Cited by 74
“More recent evidence [15,39,40] has confirmed earlier evidence [41] that the stomach must be empty for optimal absorption of L-T4; yet, some persons can absorb L-T4 adequately when food is eaten less than 1 h after ingestion of the L-T4 tablet [15,39].”
BackgroundThyroxine replacement: a clinical endocrinologist’s viewpoint
Eligar, V, Taylor, P., Okosieme, O., Leese, G., & Dayan, C. (2016) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1177/0004563216642255 · Cited by 72
Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine
Cellini, M., Santaguida, M. G., Gatto, I., Virili, C., Del Duca, S. C., Brusca, N., Capriello, S., Gargano, L., & Centanni, M. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1217 · Cited by 72
“They all agreed to take T4 under fasting conditions, waiting at least 1 hour before eating or drinking (3, 7, 16).”
BackgroundSex and Age Differences in Levothyroxine Dosage Requirement
Jonklaas, J. (2010) · Endocrine Practice · doi:10.4158/ep09257.or · Cited by 72
A. Irving, S., Vadiveloo, T., & Leese, G. P. (2015) · Clinical Endocrinology · doi:10.1111/cen.12559 · Cited by 69
Thyroxine softgel capsule in patients with gastric-related T4 malabsorption
Santaguida, M. G., Virili, C., Duca, S. C. D., Cellini, M., Gatto, I., Brusca, N., De Vito, C., Gargano, L., & Centanni, M. (2015) · Endocrine · doi:10.1007/s12020-014-0476-7 · Cited by 68
The emergence of levothyroxine as a treatment for hypothyroidism
Hennessey, J. V. (2017) · Endocrine · doi:10.1007/s12020-016-1199-8 · Cited by 66
Serum Thyrotropin Levels Following Levothyroxine Administration at Breakfast
Perez, C. L. S., Araki, F. S., Graf, H., & de Carvalho, G. A. (2013) · Thyroid · doi:10.1089/thy.2012.0435 · Cited by 63
“evaluated the effect of the timing of LT4 administration in relation to food on serum TSH (32).”
InfluentialLevothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63
Vita, R., & Benvenga, S. (2014) · Endocrine Practice · doi:10.4158/ep13316.cr · Cited by 60
Asik, M., Gunes, F., Binnetoglu, E., Eroglu, M., Bozkurt, N., Sen, H., Akbal, E., Bakar, C., Beyazit, Y., & Ukinc, K. (2014) · Endocrine · doi:10.1007/s12020-013-0065-1 · Cited by 58
Thyroxine treatment: absorption, malabsorption, and novel therapeutic approaches
Centanni, M. (2013) · Endocrine · doi:10.1007/s12020-012-9814-9 · Cited by 56
Caron, P., Grunenwald, S., Persani, L., Borson-Chazot, F., Leroy, R., & Duntas, L. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09691-9 · Cited by 53
“three-period crossover study of 65 LT4-treated stable hypothyroid patients found that nonfasting LT4 administration was associated with higher and more variable serum TSH concentrations [33].”
BackgroundAssay of Thyroid Hormones and Related Substances
Spencer, C. A. (2013) · Europe PMC (PubMed Central) · Cited by 53
Rajput, R., Chatterjee, S., & Rajput, M. (2011) · Journal of Thyroid Research · doi:10.4061/2011/505239 · Cited by 52
Levothyroxine therapy in gastric malabsorptive disorders
Virili, C., Brusca, N., Capriello, S., & Centanni, M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.621616 · Cited by 52
“In clinical practice, the timing of food intake and the interval before and after thyroxine ingestion seems not negligible for the subsequent intestinal absorption (31, 32).”
BackgroundFierabracci, P., Martinelli, S., Tamberi, A., Piaggi, P., Basolo, A., Pelosini, C., Ricco, I., Magno, S., Querci, G., Ceccarini, G., et al. (2016) · Thyroid · doi:10.1089/thy.2015.0473 · Cited by 51
“For optimal absorption, it is recommended that LT4 be taken in the fasting state in order to allow the contribution of gastric acidity and to avoid the binding of LT4 to substances that could interfere with its assimilation (13,16).”
Fallahi, P., Ferrari, S. M., Ruffilli, I., Ragusa, F., Biricotti, M., Materazzi, G., Miccoli, P., & Antonelli, A. (2016) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2016.1227782 · Cited by 48
“when L-T4 is ingested together with breakfast [27,30].”
BackgroundBrancato, D., Scorsone, A., Saura, G., Ferrara, L., Di Noto, A., Aiello, V., Fleres, M., & Provenzano, V. (2014) · Endocrine Practice · doi:10.4158/ep13418.or · Cited by 44
Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism- Correspondence.
Stott, D. J., Rodondi, N., & Bauer, D. C. (2017) · Bern Open Repository and Information System (University of Bern) · doi:10.7892/boris.110517 · Cited by 43
Oral levothyroxine therapy postbariatric surgery: Biopharmaceutical aspects and clinical effects
Azran, C., Porat, D., Fine‐Shamir, N., Hanhan, N., & Dahan, A. (2019) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2019.01.001 · Cited by 43
Oral liquid levothyroxine treatment at breakfast: a mistake?
Cappelli, C., Pirola, I., Gandossi, E., Formenti, A., & Castellano, M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-0693 · Cited by 41
Novel thyroxine formulations: a further step toward precision medicine
Virili, C., Trimboli, P., & Centanni, M. (2019) · Endocrine · doi:10.1007/s12020-019-02049-x · Cited by 41
Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2019) · Drugs in Context · doi:10.7573/dic.212597 · Cited by 41
Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism
Stott, D. J., Rodondi, N., & Bauer, D. C. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1709989 · Cited by 48
de Carvalho, G. A., Paz-Filho, G., Mesa, C. O., & Graf, H. (2018) · European Journal of Endocrinology · doi:10.1530/eje-17-0947 · Cited by 41
Azran, C., Hanhan-Shamshoum, N., Irshied, T., Ben-Shushan, T., Dicker, D., Dahan, A., & Matok, I. (2021) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2021.02.028 · Cited by 40
Ruchała, M., Szczepanek‐Parulska, E., & Zybek, A. (2012) · PubMed · Cited by 38
Treatment-refractory hypothyroidism
Ramadhan, A., & Tamilia, M. (2011) · Canadian Medical Association Journal · doi:10.1503/cmaj.110994 · Cited by 37
Thyroid hormone replacement: current status and challenges
Okosieme, O. E. (2011) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2011.600307 · Cited by 33
“By contrast, a randomized, controlled crossover study in 65 patients showed that ingesting levothyroxine 1 h before breakfast led to a better TSH response than bedtime administration [62].”
BackgroundResultCentanni, M., Duntas, L., Feldt-Rasmussen, U., Koehrle, J., Peeters, R. P., Razvi, S., Trimboli, P., & Virili, C. (2025) · European Thyroid Journal · doi:10.1530/etj-25-0123 · Cited by 38
“…dosing resulted in the highest and most variable TSH levels, while a regimen of LT4 being administered an hour before breakfast was associated with the lowest and least variable TSH; the bedtime LT4 regimen produced values and variability that was in-between the other two dosing regimens (41).”
Tanguay, M., Girard, J., Scarsi, C., Mautone, G., & Larouche, R. (2019) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.608 · Cited by 33
Skelin, M., Lucijanić, T., Liberati-Čizmek, A.-M., Klobučar, S. M., Lucijanić, M., Jakupović, L., Bakula, M., Lončar, J. V., Marušić, S., Matić, T., et al. (2018) · Endocrine · doi:10.1007/s12020-018-1686-1 · Cited by 31
Bernareggi, A., Grata, E., Pinorini, M., & Conti, A. (2013) · Pharmaceutics · doi:10.3390/pharmaceutics5040621 · Cited by 30
“Patients on treatment with T4 tablet formulations are usually informed to take the drug in the morning in fasting conditions, prior to breakfast, to avoid possible interactions with food [2–6], dietary fibers [7,8], coffee [9], coffee with milk [4], and other breakfast drinks [10] reported in the literature.”
Timing of breakfast does not influence therapeutic efficacy of liquid levothyroxine formulation
Morelli, S., Reboldi, G., Moretti, S., Menicali, E., Avenia, N., & Puxeddu, E. (2016) · Endocrine · doi:10.1007/s12020-015-0788-2 · Cited by 30
Cappelli, C., Pirola, I., Gandossi, E., Cristiano, A., Daffini, L., Agosti, B., Casella, C., & Castellano, M. (2016) · International Journal of Endocrinology · doi:10.1155/2016/9043450 · Cited by 29
Bornschein, A., Paz-Filho, G., Graf, H., & de Carvalho, G. A. (2012) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302012000400006 · Cited by 28
“(14), evaluating alternative schedules for LT4 dosing, showed that administration while fasting remains the best option.”
BackgroundThe clinical utility of free thyroxine in oral levothyroxine absorption testing
Ching Sun, G. E., Pantalone, K. M., Faiman, C., Gupta, M., Olansky, L., & Hatipoglu, B. (2014) · Endocrine Practice · doi:10.4158/ep13487.or · Cited by 27
“However, absorption of LT4 within the jejunum and ileum may be altered by a variety of factors, including timing of ingestion (2), medications (3-10), medical diseases/conditions (11-14), and/or dietary interference (15,16).”
BackgroundMedications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review
Liu, H., Lu, M., Hu, J., Fu, G., Feng, Q., Sun, S., & Chen, C. (2023) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s414460 · Cited by 29
“crossover trials in the USA and Brazil have confirmed that TSH concentrations were significantly higher in patients taking LT4 tablets with breakfast for 2–3 months.(92,93) The LT4 absorption tests uncovered the acute effects of breakfast on LT4 absorption.”
BackgroundBagattini, B., Cosmo, C. D., Montanelli, L., Piaggi, P., Ciampi, M., Agretti, P., Marco, G. D., Vitti, P., & Tonacchera, M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0621 · Cited by 28
Sheikh, A., Mawani, M., & Mahar, S. A. (2018) · Endocrine Practice · doi:10.4158/ep-2018-0038 · Cited by 26
“meal(16), thus absorption is variable and may alter TSH levels.”
BackgroundUpdate on the treatment of hypothyroidism
Jonklaas, J. (2015) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000242 · Cited by 25
The Challenges and Complexities of Thyroid Hormone Replacement
Kansagra, S. M., McCudden, C. R., & Willis, M. S. (2010) · Laboratory Medicine · doi:10.1309/lmb39th2fzgndgim · Cited by 25
Lombardi, C. P., Bocale, R., Barini, A., Barini, A., D’Amore, A., Boscherini, M., & Bellantone, R. (2017) · Endocrine · doi:10.1007/s12020-016-1003-9 · Cited by 23
L-T4 Therapy in Enteric Malabsorptive Disorders
Fallahi, P., Ferrari, S. M., Elia, G., Ragusa, F., Paparo, S. R., & Antonelli, A. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.626371 · Cited by 24
“In this study it was shown that the 1 h before breakfast ingestion has not only lower TSH values but also substantially more uniform outcomes of TSH (20).”
BackgroundPirola, I., Gandossi, E., Brancato, D., Marini, F., Cristiano, A., Delbarba, A., Agosti, B., Castellano, M., & Cappelli, C. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-018-0867-3 · Cited by 21
Ucci, S., Renzini, A., Russi, V., Mangialardo, C., Cammarata, I., Cavioli, G., Santaguida, M. G., Virili, C., Centanni, M., Adamo, S., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225754 · Cited by 21
“Importantly, in our experimental conditions, administration of T3 significantly affected the expression of numerous wellknown T3-target genes in skeletal muscle, without increasing the Dio2 expression levels in skeletal muscle, which resulted significantly down-regulated by starvation, as previously reported [55], or…”
BackgroundGuglielmi, V., Bellia, A., Bianchini, E., Medea, G., Cricelli, I., Sbraccia, P., Lauro, D., Cricelli, C., & Lapi, F. (2018) · Endocrine · doi:10.1007/s12020-017-1412-4 · Cited by 18
Park, S. H., & Hong, S. H. (2018) · Journal of Medical Internet Research · doi:10.2196/11085 · Cited by 20
“Many factors such as food, medications, and health conditions hamper the ability to maintain a desired range of thyroxine in the bloodstream [20].”
BackgroundDabbous, Z., Alowainati, B., Darwish, S., Ali, H. A., Farook, S., Malaheem, M. A., Abdalrubb, A., Gul, W., & Haliqa, W. A. (2019) · International Journal of Endocrinology · doi:10.1155/2019/9843961 · Cited by 20
Raza, S., Ishtiaq, O., Unnikrishnan, A., Khan, A. A., Ahmad, J., Ganie, M., Azad, K., Baruah, M. P., & Pathan, M. F. (2012) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.98001 · Cited by 18
“[12] While taking thyroxine in between/with food might not be best, due to variable reasons,[13] taking it at bedtime is another option, as it has shown to have almost the same effect as when taken on an empty stomach.”
Does TSH Reliably Detect Hypothyroid Patients?
Soldin, S. J. (2018) · Annals of Thyroid Research · doi:10.26420/annalsthyroidres.2018.1030 · Cited by 18
“In addition, the concentration of serum TSH is affected by a number of non-thyroid hormone factors, such as pregnancy, age, sex, exercise, individual thyroid hormone set points, the timing of levothyroxine administration, steroids, and drugs [9-17].”
BackgroundVyas, U., Sethi, B. K., & Khandelwal, D. (2018) · Thyroid Research and Practice · doi:10.4103/trp.trp_25_17 · Cited by 23
Ramadan Fasting and Changes in Thyroid Function in Hypothyroidism: Identifying Patients at Risk
Alkaf, B., Siddiqui, M., Ali, T., Bakir, A., Murphy, K. G., Meeran, K. M., & Lessan, N. G. (2022) · Thyroid · doi:10.1089/thy.2021.0512 · Cited by 16
“Timing of levothyroxine ingestion is also known to affect its absorption (7).”
BackgroundHypothyroidism and Thyroiditis
Brent, G. A., & Weetman, A. P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00013-7 · Cited by 16
Reardon, D. P., & Yoo, P. S. (2016) · Case Reports in Endocrinology · doi:10.1155/2016/1316724 · Cited by 16
“The role of gastric acid and food interactions with levothyroxine is commonly known with a proposed onehour delay between administration of levothyroxine and breakfast being recommended [9].”
BackgroundAl-Qahtani, K. M., Aldeeri, I. A., Alshaibi, A. M., Alshabib, N. S., Barghouthi, R. M., Alyusuf, E. Y., & Jammah, A. A. (2022) · Thyroid · doi:10.1089/thy.2022.0110 · Cited by 15
“Other authors have reported that taking LT4 in the morning is better for maintaining a stable TSH level (12); yet researchers from another study observed no significant change in TSH level, regardless of the timing (16).”
Managing symptoms in hypothyroid patients on adequate levothyroxine: a narrative review
Razvi, S., Mrabeti, S., & Luster, M. (2020) · Endocrine Connections · doi:10.1530/ec-20-0205 · Cited by 15
“9 levels, compared with administration in the fasting state [89].”
BackgroundDiagnosis and Management of Iatrogenic Hypothyroidism
Peterson, M. E. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-22652-3.00023-2 · Cited by 15
Islamic Fasting and Thyroid Hormones
Azizi, F. (2015) · Intern J Endocrinol Metab · doi:10.5812/ijem.13(2)2015.29248 · Cited by 15
“In contrast, a randomized crossover trail compared taking levothyroxine in the fasting state, with breakfast, or at bedtime in 65 thyroid cancer, patients with primary hypothyroidism found that fasting state and most beneficial than other times (17).”
BackgroundLevothyroxine pseudo-malabsorption: testing and treatment in the outpatient setting
Rdzak, G. M., Whitman, L. M., & Inzucchi, S. E. (2018) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018818771433 · Cited by 14
Cataldo, E., Columbano, V., Nielsen, L., Gendrot, L., Covella, B., & Piccoli, G. B. (2018) · BMC Nephrology · doi:10.1186/s12882-018-0947-9 · Cited by 14
Tortora, A., La Sala, D., & Vitale, M. (2019) · Endocrinology, Diabetes & Metabolism Case Reports · doi:10.1530/edm-19-0026 · Cited by 13
Controlled delivery of levothyroxine using porous silicon as a drug nanocontainer
Kashanian, S., Rostami, E., Harding, F. J., McInnes, S. J. P., Al-Bataineh, S., & Voelcker, N. H. (2016) · Australian Journal of Chemistry · doi:10.1071/ch15315 · Cited by 13
Ducharme, M., Scarsi, C., Bettazzi, E., Mautone, G., Lewis, Y., & Celi, F. S. (2022) · Thyroid · doi:10.1089/thy.2021.0604 · Cited by 13
Should the dose of levothyroxine be changed in hypothyroidism patients fasting during Ramadan?
Koca, A. O., Dağdeviren, M., & Altay, M. (2020) · TURKISH JOURNAL OF MEDICAL SCIENCES · doi:10.3906/sag-1911-28 · Cited by 13
Stagi, S., Municchi, G., Ferrari, M., & Wasniewska, M. G. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.859487 · Cited by 15
“Tablets should be taken at least 1 h before breakfast (60).”
BackgroundLiquid levothyroxine formulations in patients taking drugs interfering with L-T4 absorption
Gatta, E., Bambini, F., Buoso, C., Gava, M., Maltese, V., Anelli, V., Delbarba, A., Pirola, I., & Cappelli, C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1080108 · Cited by 15
El-Kaissi, S., Dajani, R. Z., John, T. J. L.-S., Santarina, S. A., Makia, F., AlTakruri, M., & Ahmed, Y. (2020) · Endocrine Practice · doi:10.4158/ep-2019-0505 · Cited by 13
Carbimazole-Induced Acute Pancreatitis and Cholestatic Hepatitis
Chng, C. L., Kek, P. C., Khoo, D. H. C., Granata, A. R. M., Floccari, F., & Gallieni, M. A. (2011) · Endocrine Practice · doi:10.4158/ep.17.6.960 · Cited by 12
Marina, M., Ceda, G. P., Aloe, R., Gnocchi, C., & Ceresini, G. (2016) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 12
Attanasio, R., Žarković, M., Papini, E., Nagy, E. V., Negro, R., Perros, P., Akarsu, E., Alevizaki, M., Ayvaz, G., Bednarczuk, T., et al. (2024) · Thyroid® · doi:10.1089/thy.2023.0580 · Cited by 11
“61,62 Notably, the switch from LT4 tablets to different formulations in case of unexplained poor control of hypothyroidism was reported more frequently by the young physicians and by those who work in private practice.”
Best Time for Levothyroxine Intake in Ramadan (THYRAM): Basrah Experience
Zaboon, I. A., Alidrisi, H. A., Hussein, I. H., Alabbood, M., Alibrahim, N. T. Y., Almomin, A., Al-Waeli, D. K., Alhamza, A. H. A., Mohammed, A. G., Nwayyir, H. A., et al. (2020) · Intern J Endocrinol Metab · doi:10.5812/ijem.94325 · Cited by 11
“In addition, two studies found that L-thyroxine intake was better at bedtime than in the morning (16, 17).”
BackgroundResultDose administration time from before breakfast to before dinner affect thyroid hormone levels?
Ala, S., Akha, O., Kashi, Z., Asgari, H., Bahar, A., & Sasanpour, N. (2015) · PubMed Central · Cited by 11
Lewandowski, K. C., Dąbrowska, K., Komorowska-Dudek, I., & Lewiński, A. (2015) · Thyroid Research · doi:10.1186/s13044-015-0028-0 · Cited by 10
“[9] demonstrated that even with full compliance, an ingestion of L-T4 tablets within 20 min of breakfast results in more than 100 % increase in mean TSH concentrations (1.”
Background
Metadata
- Authors
- Bach-Huynh, T.-G., Nayak, B., Loh, J., Soldin, S., & Jonklaas, J.
- Affiliations
- Georgetown University Medical Center (US)
- Corresponding author
- Jonklaas, Jacqueline
- ORCID
- Jonklaas, Jacqueline
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-10-01
- Volume
- 94
- Issue
- 10
- Pages
- 3905-3912
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2758731
- OpenAlex
- W2110073453
- Cited by
- 198
- References
- 30
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 7 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 11 · 2018: 19 · 2017: 10 · 2016: 21 · 2015: 16 · 2014: 12 · 2013: 11 · 2012: 14
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Center for Research Resources (K23 RR16524, M01RR020359, MO1-RR-020359, K23RR016524)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- levothyroxine, timing of drug administration, serum thyrotropin, thyroid-stimulating hormone, dietary intake, fasting, hypothyroidism, thyroid cancer, free thyroxine, total T3, drug absorption
- MeSH terms
- Administration, Oral, Adult, Aged, Drug Administration Schedule, Fasting, Female, Humans, Hypothyroidism, Male, Middle Aged, Thyroid Hormones, Thyroid Neoplasms, Thyrotropin, Thyroxine, Time Factors, Cross-Over Studies, Hormone Replacement Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
