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

Abstract

Levothyroxine (LT4) is recommended for intake in a fasting state to optimize absorption. However, fasting intake is often burdensome and may reduce adherence. In a previous questionnaire study, we observed a strong patient preference for taking LT4 with breakfast. Therefore, we conducted a randomized controlled trial to evaluate whether nonfasting LT4 intake-accompanied by a 15% dose increase-could maintain TSH stability compared to fasting LT4 intake. Adults with well-controlled hypothyroidism were randomized to fasting or dose-adjusted, breakfast LT4 intake. TSH, free T4, and total T3 were measured every 6 weeks, followed by LT4 dose adjustment if needed. The primary outcome was TSH stability, 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. After the initial study period, patients in the fasting group were invited to cross over to nonfasting intake, with similar follow-up. Eighty-eight patients (80.7% female, median age 62y [interquartile range: 49-69]) were randomized to fasting (n = 43) or breakfast intake (n = 45). TSH stability was comparable between groups: 74.4% [95% confidence interval (CI): 61.0-88.0%] in the fasting vs 73.3% (95%CI: 60.0-87.0%) in the breakfast group (P = not significant). Similar findings were observed in the crossover group. The breakfast group reported greater improvement in self-reported well-being (33.3% vs 16.3%, P = .07) and a stronger preference for nonfasting intake (76.2% vs 44.2%, P < .001). By the end of the study, 88.9% chose to continue nonfasting intake. LT4 ingestion with breakfast with a 15% dose increase maintained TSH stability and improved patient well-being. Given the strong patient preference, this patient-centered approach may offer a viable alternative to fasting administration.