, Volume 43, Issue 1, pp 154–160 | Cite as

A novel formulation of l-thyroxine (l-T4) reduces the problem of l-T4 malabsorption by coffee observed with traditional tablet formulations

  • Roberto VitaEmail author
  • Giovanna Saraceno
  • Francesco Trimarchi
  • Salvatore Benvenga
Original Article


The purpose of this work is to evaluate if the coffee-associated malabsorption of tablet levothyroxine (l-T4) is reduced by soft gel capsule. We recruited 8 patients with coffee-associated l-T4 malabsorption including one hypothyroid patient. For 6 months, the patients were switched to the capsule maintaining the l-T4 daily dose. Patients took the capsule with water, having coffee 1 h later (proper habit, PH) on days 1–90, or with coffee ≤5 min later (improper habit, IH) on days 91–180. After 6 months, 2 patients volunteered for an acute loading test of 600 μg l-T4 (capsule) ingested with water (PH) or with coffee (IH). In the single hypothyroid patient, the post-switch TSH ranged 0.06–0.16 mU/L (PH) versus 5.8–22.4 mU/L pre-switch (PH) and 0.025–0.29 mU/L (IH) versus 26–34 mU/L pre-switch (IH). In the other 7 patients, post-switch TSH was 0.41 ± 0.46 (PH) versus 0.28 ± 0.20 pre-switch (PH) (P = 0.61) and 0.34 ± 0.30 (IH) versus 1.23 ± 1.47 pre-switch (IH) (P < 0.001). Importantly, TSH levels in PH versus IH habit did not differ post-switch (P = 0.90), but they did pre-switch (P < 0.0001). The proportions of post-switch TSH levels <0.10 mU/L with PH (33.3 %) or with IH (33.3 %) were borderline significantly greater than the corresponding pre-switch levels with PH (10.3 %) (P = 0.088) or with IH (0 %) (P = 0.0096). In the two volunteers, the l-T4 loading test showed that coffee influenced l-T4 pharmacokinetics minimally. Soft gel capsules can be used in patients who are unable/unwilling to change their IH of taking l-T4.


l-Thyroxine therapy l-T4 formulations l-Thyroxine malabsorption Coffee Hypothyroidism 


Conflict of interest

IBSA Institut Biochimique SA (Lugano, Switzerland) furnished the principal investigator (S.B.) with the capsules for the entire duration of the study.


  1. 1. (2012). Accessed 11 Jan 2012
  2. 2.
    D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L. Mazzaferri, B. McIver, F. Pacini, M. Schlumberger, S.I. Sherman, D.L. Steward, R.M. Tuttle, Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167–1214 (2009)PubMedCrossRefGoogle Scholar
  3. 3.
    N.R. Rose, I.R. Mackay, The Autoimmune Diseases, 3rd edn (1998). Accessed 11 Jan 2012
  4. 4.
  5. 5.
    M.J. Vanderpump, The epidemiology of thyroid diseases, in Werner and Ingbar’s The Thyroid. A fundamental and Clinical Text, vol. 9, ed. by L.E. Braverman, R.D. Utiger (Lippincott Williams & Wilkins, Philadelphia, 2005), pp. 398–406Google Scholar
  6. 6.
    S. Benvenga, F. Trimarchi, Changed presentation of Hashimoto’s thyroiditis in North-Eastern Sicily and Calabria (Southern Italy) based on a 31-year experience. Thyroid 18, 429–441 (2008)PubMedCrossRefGoogle Scholar
  7. 7.
    L. Santarpia, M. Valenzise, G. Di Pasquale, T. Arrigo, G. San Martino, M.P. Cicciò, F. Trimarchi, F. De Luca, S. Benvenga, TTF2/FOXE1 gene polymorphisms in Sicilian patients with permanent primary congenital hypothyroidism. J. Endocrinol. Investig. 30, 13–19 (2007)Google Scholar
  8. 8.
    G. Van Vliet, Hypothyroidsm in infants and children: congenital hypothyroidism, in Werner and Ingbar’s The Thyroid. A Fundamental and Clinical Text, vol. 9, ed. by L.E. Braverman, R.D. Utiger (Lippincott Williams & Wilkins, Philadelphia, 2005), pp. 1033–1041Google Scholar
  9. 9.
    M.J. Lamson, C.L. Pamplin, R.L. Rolleri, I. Klein, Quantitation of a substantial reduction in levothyroxine (T4) absorption by food. Thyroid 14, 876 (2004)Google Scholar
  10. 10.
    T.G. Bach-Huynh, B. Nayak, J. Loh, S. Soldin, J. Jonklaas, Timing of levothyroxine administration affects serum thyrotropin concentration. J. Clin. Endocrinol. Metab. 94, 3905–3912 (2009)PubMedCrossRefGoogle Scholar
  11. 11.
    S. Benvenga, L. Bartolone, S. Squadrito, F. Lo Giudice, F. Trimarchi, Delayed intestinal absorption of levothyroxine. Thyroid 5, 249–253 (1995)PubMedCrossRefGoogle Scholar
  12. 12.
    L. Liwanpo, J.M. Hershman, Conditions and drugs interfering with thyroxine absorption. Best Pract. Res. Clin. Endocrinol. Metab. 23, 781–792 (2009)PubMedCrossRefGoogle Scholar
  13. 13.
    D. Collins, R. Wilcox, M. Nathan, R. Zubarik, Celiac disease and hypothyroidism. Am. J. Med. 125, 278–282 (2012)PubMedCrossRefGoogle Scholar
  14. 14.
    C. Virili, G. Bassotti, M.G. Santaguida, R. Iuorio, S.C. Del Duca, V. Mercuri, A. Picarelli, P. Gargiulo, L. Gargano, M. Centanni, Atypical celiac disease as cause of increased need for thyroxine: a systematic study. J. Clin. Endocrinol. Metab. 97, E419–E422 (2012)PubMedCrossRefGoogle Scholar
  15. 15.
    R. Padwal, D. Brocks, A.M. Sharma, A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes. Rev. 11, 41–50 (2010)PubMedCrossRefGoogle Scholar
  16. 16.
    A. Tönjes, S. Karger, C.A. Koch, R. Paschke, A. Tannapfel, M. Stumvoll, D. Fuhrer, Impaired enteral levothyroxine absorption in hypothyroidism refractory to oral therapy after thyroid ablation for papillary thyroid cancer: case report and kinetic studies. Thyroid 16, 1047–1051 (2006)PubMedCrossRefGoogle Scholar
  17. 17.
    L. Anderson, F. Joseph, N. Goenka, V. Patel, Isolated thyroxine malabsorption treated with intramuscular thyroxine injections. Am. J. Med. Sci. 337, 150–152 (2009)PubMedCrossRefGoogle Scholar
  18. 18.
    S. Benvenga, L. Bartolone, M.A. Pappalardo, A. Russo, D. Lapa, G. Giorgianni, G. Saraceno, F. Trimarchi, Altered intestinal absorption of l-thyroxine caused by coffee. Thyroid 18, 293–301 (2008)PubMedCrossRefGoogle Scholar
  19. 19.
    A. Sindoni, R. Vita, S. Fusco, G. Saraceno, M.A. Pappalardo, O.R. Cotta, S. Grasso, F. Trimarchi, S. Benvenga, Case report. Coffee impairs intestinal absorption of levothyroxine: report of additional cases. Hot Thyroidol. HT05/09, April 2009 (
  20. 20.
  21. 21.
    P. Colucci, P. D’Angelo, G. Mautone, C. Scarsi, M.P. Ducharme, Pharmacokinetic equivalence of a levothyroxine sodium soft capsule manufactured using the new food and drug administration potency guidelines in healthy volunteers under fasting conditions. Ther. Drug Monit. 33, 355–361 (2011)PubMedCrossRefGoogle Scholar
  22. 22.
  23. 23.
  24. 24.
  25. 25.
    T.H. Collet, J. Gussekloo, D.C. Bauer, W.P. den Elzen, A.R. Cappola, P. Balmer, G. Iervasi, B.O. Asvold, J.A. Sgarbi, H. Völzke, B. Gencer, R.M. Maciel, S. Molinaro, A. Bremner, R.N. Luben, P. Maisonneuve, J. Cornuz, A.B. Newman, K.T. Khaw, R.G. Westendorp, J.A. Franklyn, E. Vittinghoff, J.P. Walsh, N. Rodondi, The thyroid studies collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch. Intern. Med. 172, 799–809 (2012)PubMedCrossRefGoogle Scholar
  26. 26.
    G. Mazziotti, T. Porcelli, I. Patelli, P.P. Vescovi, A. Giustina, Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density. Bone 46, 747–751 (2010)PubMedCrossRefGoogle Scholar
  27. 27.
    M.P. Ducharme, S. Benvenga, Comparison of the intestinal absorption of levothyroxine (LT4): tablet versus soft gel capsule formulation. Endocr. Rev. 32, P3–P625 (2011)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Roberto Vita
    • 1
    Email author
  • Giovanna Saraceno
    • 1
  • Francesco Trimarchi
    • 1
  • Salvatore Benvenga
    • 1
    • 2
    • 3
  1. 1.Section of Endocrinology, Department of Clinical and Experimental Medicine & PharmacologyUniversity of Messina, A.O.U. Policlinico G. MartinoMessinaItaly
  2. 2.Master of Childhood, Adolescent and Women’s Endocrine HealthUniversity of Messina, A.O.U. Policlinico G. MartinoMessinaItaly
  3. 3.Interdepartmental Program of Molecular & Clinical Endocrinology, and Women’s Endocrine HealthUniversity Hospital of Messina, A.O.U. Policlinico G. MartinoMessinaItaly

Personalised recommendations