Vitamins, Supplements, and Dietary Habits Contribute to Incorrect Levothyroxine Administration – A Sub-Analysis of the CONTROL Surveillance II Study
Main Article Content
Abstract
Introduction: Levothyroxine has a narrow therapeutic window, and its absorption is highly sensitive to food and supplements, making precise dosing and adherence to administration guidelines critical. The CONTROL Surveillance II study evaluated real-world patient awareness and adherence to FDA-labeled levothyroxine administration instructions, including timing and avoidance of interfering substances. This sub-analysis assessed patient ingestion of foods, vitamins, and supplements known to affect absorption, the effectiveness of physician communication, and patient comprehension and recall, as well as demographic and socioeconomic characteristics associated with lower awareness.
Methods: CONTROL Surveillance II was an online survey of 1,000 U.S. adults aged 19–90 years who self-reported a clinician diagnosis of hypothyroidism. Participants were randomly selected from a proprietary, consented research panel developed and maintained by Harmon Research Inc., a U.S.-based research firm (https://www.harmonresearch.com). Pregnant patients were excluded. Qualified subjects had been taking levothyroxine monotherapy for ≥ 1 year. Survey questions were reviewed by board certified endocrinology experts, and the survey was initiated in December 2023 and completed in January 2024.
Results: This CONTROL Surveillance II sub-analysis assessed patient awareness of food, vitamin, and supplement interactions with levothyroxine, provider communication, and factors associated with nonadherence. Key findings include: 1. Overall, 49% of participants reported using dietary supplements, most commonly multivitamins (57%), followed by calcium (30%) and iron (15%). 2. Most patients recalled receiving physician guidance on dosing timing, but only 45% remembered discussions about food, vitamin, or supplement interactions with levothyroxine. 3. Supplement use was higher among older adults (29% vs 14%, P≤ 0.05), non-Hispanic white patients (27% v 18%, P≤ 0.05), and higher income participants, with the latter reporting greater multivitamin and calcium use than lower-income groups (63% vs 54% and 39% vs 28%, P≤ 0.05).
Conclusions: Suboptimal levothyroxine administration due to supplement and food co-administration is widespread. This sub-analysis highlights persistent gaps in counseling and comprehension influenced by sociodemographic factors, underscoring the need for improved patient education.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. American Thyroid Association, “Thyroid Hormone Treatment,” American Thyroid Association, 2024, https://www.thyroid.org/thyroid-hormone-treatment. Accessed October 21, 2024.
3. Donnelly M, Fang L, Madabushi R, et al. Narrow Ther¬apeutic Index Drugs: FDA Experience, Views, and Op¬erations. Clin Pharmacol Ther. 2025;117(1):116-129. doi:10.1002/cpt.3460.
4. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24:1670-1751.
5. Centanni M, Duntas L, Feldt-Rasmussen U, et al. ETA guidelines for the use of levothyroxine sodium prepa¬rations in monotherapy to optimize the treatment of hypothyroidism. Eur Thyroid J. 2025;14(4):e250123. doi: 10.1002/cpt.3460.
6. McMillan M, Rotenberg KS, Vora K, et al. Comorbidi-ties, concomitant medications, and diet as factors af-fecting levothyroxine therapy: results of the CON-TROL Surveillance Project. Drugs R D. 2016;16:53-68. doi: 10.1007/s40268-015-0116-6.
7. Cummings-John D, Sandulli W, Castano M, Clark D, Heidel RE. Drug administration as a factor affecting levothyroxine therapy—results of the CONTROL sur-veillance II study. Ann Thyroid. 2025;10:4.
8. Ward LS. The difficult patient: drug interaction and the influence of concomitant diseases on the treatment of hypothyroidism. Arq Bras Endocrinol Metabol. 201 0;54:435-442. doi: 10.1590/s0004-27302010000 500002.
9. Badillo R, Francis D. Diagnosis and treatment of gas-troesophageal reflux disease. World J Gastrointest Pharmacol Ther. 2014;5:105-112. doi: 10.4292/wjgpt.v5.i3.105.
10. Cohen E, Bolus R, Khanna D, et al. GERD symptoms in the general population: prevalence and severity ver-sus care-seeking patients. Dig Dis Sci. 2014;59:2488-2496.
11. Ruchala M, Szczepanek-Parulska E, Zybek A. The in-fluence of lactose intolerance and other gastro-intes-tinal tract disorders on L-thyroxine absorption. En-dokrynol Pol. 2012;63:318-323.
12. Moraga Franco CR, Falbe J, Arnold CD, Engle-Stone R. The Food Fortification Landscape in the United States: Identification and Prevalence of Fortified Food Purchases Using National Household Scanner Data. J Nutr. 2025;155(10):3321-3335. doi:10.1016/j.tjnut.2025.08.015.
13. American Dietetic Association. Position of the Ameri-can Dietetic Association: fortification and nutritional supplements. J Am Diet Assoc. 2005;105(8):1300-1311. doi:10.1016/j.jada.2005.06.009.
14. Sadovsky R, Collins N, Tighe AP, Brunton SA, Safeer R. Patient use of dietary supplements: a clinician's per¬spective. Curr Med Res Opin. 2008;24(4):1209-1216. doi:10.1185/030079908x280743.
15. Bailey RL, Gahche JJ, Lentino CV, Dwyer JT, Engel JS, Thomas PR, Betz JM, Sempos CT, Picciano MF. Dietary supplement use in the United States, 2003-2006. J Nutr. 2011;141:261-266.
16. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283(21):2822-2825. doi:10.1001/jama.283.21.2822.
17. Mehuys E, Lapauw B, T’Sjoen G, et al. Investigating Levothyroxine Use and Its Association with Thyroid Health in Patients with Hypothyroidism: A Community Pharmacy Study. Thyroid®. 2023;33(8):918-926. doi:10.1089/thy.2023.0066.
18. Irving SA, Vadiveloo T, Leese GP. Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol (Oxf). 2015;82:136-141. doi: 10.1111/cen.12559.
19. Shkembi B, Huppertz T. Calcium Absorption from Food Products: Food Matrix Effects. Nutrients. 2021;14(1):180. doi:10.3390/nu14010180.
20. Cowan AE, Jun S, Gahche JJ, et al. Dietary Supple-ment Use Differs by Socioeconomic and Health-Re-lated Characteristics among U.S. Adults, NHANES 2011-2014. Nutrients. 2018;10(8):1114. doi:10.3390/nu10081114.
21. Gahche JJ, Bailey RL, Potischman N, Dwyer JT. Dietary Supplement Use Was Very High among Older Adults in the United States in 2011-2014. J Nutr. 2017;147(10):1968-1976. doi:10.3945/jn.117.255984.
22. McGilton KS, Vellani S, Yeung L, et al. Identifying and understanding the health and social care needs of older adults with multiple chronic conditions and their caregivers: a scoping review. BMC Geriatr. 2018;18(1):231. doi: 10.3945/jn.117.255984.
23. Gualtieri L, Rigby M, Wang D, Mann E. Medication Management Strategies to Support Medication Ad-herence: Interview Study With Older Adults. Interact J Med Res. 2024;13:e53513. doi:10.2196/53513.
24. Coughlin SS, Vernon M, Hatzigeorgiou C, George V. Health Literacy, Social Determinants of Health, and Disease Prevention and Control. J Environ Health Sci. 2020;6(1):3061.
25. Kwon DH, Kwon YD. Patterns of health literacy and influencing factors differ by age: a cross-sectional study. BMC Public Health. 2025;25(1):1556. doi:10.1186/s12889-025-22838-6.
26. Kennedy J. Herb and supplement use in the US adult population. Clin Ther. 2005;27(11):1847-58. doi: 10.1016/j.clinthera.2005.11.004.
27. McFarland MS, Finks SW, Smith L, et al. Medication Optimization: Integration of Comprehensive Medica-tion Management into Practice. Am Health Drug Bene¬fits. 2021;14(3):111-114.
28. McCabe, Beverly J. Prevention of food-drug interac-tions with special emphasis on older adults. Curr Opin Clin Nutr Metab Care. 2004;7(1):21-26. doi: 10.1097/00075197-200401000-00005.
29. Rahayu SA, Widianto S, Defi IR, Abdulah R. Role of Pharmacists in the Interprofessional Care Team for Pa¬tients with Chronic Diseases. J Multidiscip Healthc. 2021;14:1701-1710. doi:10.2147/JMDH.S309938.
30. Hickson M, Child J, Collinson A. A case study of the impact of a dietitian in the multi-disciplinary team within primary care: a service evaluation. J Hum Nutr Diet. 2023;36(5):1760-1770. doi:10.1111/jhn.13217.
31. The importance of dieticians as healthcare work-ers. Cardiovasc J Afr. 2021;32(3):132.
32. Dew R, King K, Okosieme OE, et al. Attitudes and per¬ceptions of health professionals towards management of hypothyroidism in general practice: a qualitative interview study. BMJ Open. 2018;8(2):e019970. doi:10.1136/bmjopen-2017-019970.
33. Galmarini E, Marciano L, Schulz PJ. The effectiveness of visual-based interventions on health literacy in health care: a systematic review and meta-analysis. BMC Health Serv Res. 2024;24(1):718. doi:10. 1186/s12913-024-11138-1.
34. Smets EMA, Menichetti J, Lie HC, Gerwing J. What do we mean by “tailoring” of medical information during clinical interactions? Patient Educ Couns. 2024;119:108092. doi:10.1016/j.pec.2023.108092.
35. Yu J, Lee J, Yang Y, Lee EY, Lee SH, Cho JH. Clinical Impact of Personalized Physician's Education and Re-mote Feedback Via a Digital Platform on Glycemic Control: Pilot Randomized Controlled Trial. JMIR Mhealth Uhealth. 2025;13:e67151. doi:10.2196/67 151.
36. Meneses JK, Muniz DA, Moroto D, Martins JRM, Janovsky CCPS. The Influence of Health Literacy on the Control of Hypothyroidism in Patients Under Levo¬thyroxine Treatment. Clin Endocrinol (Oxf). 2026;104(2):167-174. doi:10.1111/cen.70047.
37. Merks P, Cameron J, Bilmin K, et al. Medication Ad-herence and the Role of Pictograms in Medication Counselling of Chronic Patients: a Review. Front Phar¬macol. 2021;12:582200. doi:10.3389/fphar.2021.582200.
38. Farre A, Huckerby L, Gray NJ, Fulton R, McDonagh JE. Adolescents’ and Young Adults’ Adherence to Medi¬cation During the Transition to Adult Healthcare: A De¬velopmentally Appropriate Framework for Optimis¬ing Adherence-Promoting Interventions. Paediatr Drugs. 2026;28(1):5-13. doi:10.1007/s40272-025-00724-3.
39. IQVIA. National Prescription Audit. Published August 30, 2024. Accessed October 21, 2024. https://www.iqvia.com