Fasting vs Nonfasting, Dose-adjusted Levothyroxine Ingestion in Hypothyroidism: A Randomized Clinical Trial.

TSH stability was comparable between fasting and dose-adjusted breakfast LT4 intake groups.

• TSH stability was achieved in 74.4% (95% CI: 61.0-88.0%) of the fasting group vs 73.3% (95% CI: 60.0-87.0%) in the breakfast group (P = not significant).
• TSH stability was defined as 2 consecutive values within the reference range and a maximum ±1 mIU/L change from baseline.
• Patients were followed until TSH stability was reached, with a maximum of 24 weeks, with TSH, free T4, and total T3 measured every 6 weeks.
• Similar findings were observed in the crossover group, where fasting group patients crossed over to nonfasting intake with similar follow-up.

The breakfast group reported greater improvement in self-reported well-being compared to the fasting group.

• 33.3% of the breakfast group reported improved well-being vs 16.3% in the fasting group (P = .07).
• The difference did not reach conventional statistical significance (P = .07).
• 88 patients were randomized overall (80.7% female, median age 62 years, interquartile range: 49-69).

Patients in the breakfast group expressed a significantly stronger preference for nonfasting LT4 intake compared to the fasting group.

• 76.2% of the breakfast group preferred nonfasting intake vs 44.2% of the fasting group (P < .001).
• By the end of the study, 88.9% of all patients chose to continue nonfasting intake.
• A prior questionnaire study by the same group had observed a strong patient preference for taking LT4 with breakfast, motivating this trial.

The study population consisted of adults with well-controlled hypothyroidism randomized to fasting or breakfast LT4 intake with a 15% dose increase in the breakfast group.

• 43 patients were randomized to fasting intake and 45 to breakfast intake.
• The breakfast group received a 15% dose increase to compensate for expected reduced absorption when taken with food.
• LT4 dose adjustment was performed every 6 weeks if TSH values were outside the reference range.
• After the initial study period, patients in the fasting group were invited to cross over to nonfasting intake with similar follow-up.

Fasting LT4 intake is recommended to optimize absorption but is considered burdensome and may reduce adherence.

• Current guidelines recommend LT4 intake in a fasting state to optimize absorption.
• A previous questionnaire study by the authors observed a strong patient preference for taking LT4 with breakfast.
• This patient burden and preference gap motivated the investigation of a dose-adjusted nonfasting alternative.