From HealthCentral.com: "Levothyroxine is the second-most-prescribed drug in the US, with more than 102 million prescriptions in 2019. Historically, people were advised to take their pill first thing in the morning, on an empty stomach, and wait at least an hour before having breakfast. This is because a number of foods and beverages can interfere with its absorption, including milk, soy, coffee, papaya, and grapefruit.

More recently, the American Thyroid Association has endorsed two options for levothyroxine timing: either first thing in the morning, at least an hour before eating, or at bedtime, several hours after eating dinner.
Many studies have looked at whether one of these options is better than the other in terms of ensuring maximum absorption of oral levothyroxine, which is a synthetic form of the thyroid hormone T4 and most often prescribed to treat hypothyroidism (underactive thyroid). Newer research, including a meta-analysis published in 2020 in Clinical Endocrinology, suggests that taking levothyroxine at night may actually hold a slight edge over taking it in the a.m. But experts we spoke with voted for whichever time is more convenient for you, and more importantly, when you are most likely to remember the medication.

Taking at Night - Is Bedtime Better?
In the systematic review and meta-analysis published in 2020, researchers from North Sichuan Medical College in China analyzed data from 10 prospective or randomized controlled trials conducted in seven countries comparing levothyroxine schedules at morning to bedtime. Studies were conducted between 2001 and 2018, with duration ranging between two and six months. All formulations of levothyroxine were in oral tablet form.

Findings showed that across studies, taking levothyroxine before breakfast compared with before bedtime had no significant difference on the level of thyroid-stimulating hormone (TSH), an indicator of whether a person has adequate thyroid hormone in their system. However, in an additional analysis performed on nine studies, researchers found that levothyroxine administered at bedtime was associated with a higher free thyroxine (T4) level when compared with breakfast administration.

Although the finding did not reach statistical significance, these results appeared to “favor” a bedtime dose, the researchers wrote. One possible explanation they offered was that about 60% to 82% of levothyroxine is absorbed over three hours, so the one-hour interval before eating breakfast may not be sufficient. They also noted that a high-fat, large American-style breakfast may impact absorption of the drug.

Preference - A Matter of Choice: Experts we interviewed framed the choice of a morning or bedtime dose as mainly a matter of patient convenience.

“In general, it really doesn’t matter what time a patient takes their levothyroxine,” says David S. Cooper, M.D., MACP, director of the Thyroid Clinic and professor of medicine in the Division of Endocrinology, Diabetes, and Metabolism at Johns Hopkins University School of Medicine, in an email.