BACKGROUND
Hypothyroidism occurs when the thyroid stops working and thyroid hormone levels fall into the low range. Treatment of hypothyroidism is usually levothyroxine to replace the thyroid hormones in the blood. The absorption of levothyroxine is affected by acid levels in the stomach. Taking levothyroxine with food, iron, calcium, or certain medications used for gastritis or reflux disease can decrease levothyroxine absorption and its efficacy. Therefore, patients are advised to take levothyroxine in an empty stomach and wait at least 30-60 minutes before eating breakfast. However, some patients may find this recommendation difficult to follow due to various circumstances, leading to missed or decreased effectiveness of levothyroxine and inadequate treatment of hypothyroidism.

The researchers of the study aimed to assess if taking a higher dose of levothyroxine with breakfast would still result in stable thyroid function compared to taking a lower dose of levothyroxine before breakfast.

THE FULL ARTICLE TITLE
Willems JIA, et al. Fasting vs non‑fasting, dose‑adjusted levothyroxine ingestion in hypothyroidism: a randomized clinical trial. J Clin Endocrinol Metab. Epub 2025 Dec 23; doi: 10.1210/clinem/dgaf686. PMID: 41431302.

SUMMARY OF THE STUDY
A total of 88 patients with hypothyroidism taking levothyroxine were enrolled in this clinical trial done in the Netherlands. Patients were taking at least 1mcg/kg of levothyroxine every day and had stable serum TSH levels prior to the study. Patients were not included if they had history of thyroid or other cancers, malabsorption disorders, other severe chronic disease such as advanced heart failure or end-stage kidney disease, or if pregnant.

Patients were divided to either the fasting group (43 patients taking levothyroxine 30-60 minutes before breakfast) or the breakfast group (45 patients taking levothyroxine with breakfast). Levothyroxine dose was increased by 15% for patients in the breakfast group to make up for lower absorption. TSH level was measured every 6 weeks with appropriate adjustment of levothyroxine dose, until it was stable over 2 consecutive checks or until 24 weeks after study started (the end of the study).

Patients also answered questionnaires regarding their overall well-being and preferred regimen. At the end of the study, all 43 patients in the initial fasting group were invited to change to the breakfast regimen. Those who participated further by switching to the breakfast regimen were referred to as the crossover group.

Similar number of patients achieved stable TSH levels in both groups, including 74.4% in the fasting group and 73.3% in the breakfast group. The average time for reaching stable TSH level was 12 weeks, similar in both groups. More patients in the breakfast group (33.3%) reported improvement in well-being compared to those in the fasting group (16.3%). Reasons for improvement in well-being in the breakfast group included feeling more fit, less stress and easier adherence with regimen, decrease in stomach discomfort after switching to taking levothyroxine with breakfast, and more consistent breakfast routine. At the end of the study, 89% of the patients in the breakfast group opted to continue taking levothyroxine with breakfast.

Among the 32 patients in the fasting group whose TSH levels were stable, 18 patients opted to crossover to the breakfast regimen with levothyroxine dose increase, with 66.7% achieving stable TSH level. No significant change was seen in their overall well-being after crossover, but 78% of these patients preferred taking levothyroxine with breakfast over fasting.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The researchers of this study concluded that stable TSH levels can be achieved with 15% increase in levothyroxine dose if patients take levothyroxine with breakfast consistently. Patients in this study also preferred taking levothyroxine with breakfast over fasting. Previous studies by the researchers of this study reported that 50% of patients found taking levothyroxine before breakfast burdensome and 33% of patients were not taking it consistently. This study shows that taking a slightly higher dose of levothyroxine with breakfast may be a practical option to improve consistency and to achieve treatment target in patients with well-controlled hypothyroidism.

— Sun Y. Lee, MD

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