March 03, 2020
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Bedtime vs. breakfast levothyroxine administration may boost free thyroxine level

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Adults with hypothyroidism taking levothyroxine therapy may derive a greater benefit when taking the drug at bedtime vs. before breakfast, according to findings published in Clinical Endocrinology.

“The timing of levothyroxine administration has become a hot topic in recent years,” Ru Sun, of the department of blood transfusion at the Affiliated Hospital of North Sichuan Medical College, China, and colleagues wrote in the study background. “The Chinese Society of Endocrinology recommends that levothyroxine should be consistently taken 60 minutes before breakfast. However, the American Thyroid Association recommends that, if possible, levothyroxine be consistently taken either 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal), for optimal, consistent absorption. Recently, some studies have been conducted in which the efficacy of levothyroxine administration before breakfast and at bedtime were compared. Some studies reported that the efficiency of levothyroxine at bedtime was better than administration before breakfast. However, other studies showed no significant difference with bedtime vs. morning intake.”

In a systematic review and meta-analysis, Sun and colleagues analyzed data from 10 prospective or randomized controlled trials conducted in seven countries comparing levothyroxine administration before breakfast to administration at bedtime among patients with hypothyroidism (n = 687). Studies were conducted between 2001 and 2018, with duration ranging between 2 and 6 months. All formulations of levothyroxine were in tablet form. Researchers used random- and fixed-effects models to estimate pooled effects of levothyroxine administration at breakfast vs. bedtime on thyroid hormone levels.

Researchers found that levothyroxine administration before breakfast compared with before bedtime had no significant difference on thyroid-stimulating hormone level across studies (standardized mean difference [SMD] = 0.09; 95% CI, –0.12 to 0.3). In six of the studies, researchers found that levothyroxine administration before breakfast vs. at bedtime similarly had no effect on free triiodothyronine (SMD = –0.19, 95% CI, –0.53 to 0.15).

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Adults with hypothyroidism taking levothyroxine therapy may derive a greater benefit when taking the drug at bedtime vs. before breakfast.
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In a random-effect analysis performed on nine studies, researchers found that levothyroxine administered at bedtime was associated with a higher free thyroxine level when compared with breakfast administration (SMD = –0.27; 95% CI, –0.52 to –0.02).

“Even though there were no statistical differences, the result of TSH or free T3 seemed [to] ‘favor’ bedtime,” the researchers wrote. “This situation may be explained on the basis of several factors. On one hand, approximately 60% to 82% of the administered dose is mostly absorbed during the 3 hours after administration of the drug. Thus, a 1-hour interval does not seem to be sufficient. In addition, breakfast may contain foods that could affect the absorption of levothyroxine, such as coffee, soybeans and fiber. A breakfast with a higher caloric content or higher protein or fat content, as is frequent in Europe and North America, could cause greater interference in levothyroxine absorption.”

The researchers concluded that levothyroxine administration at bedtime may be an “attractive option” for patients with hypothyroidism.

“Further exploration, including well-designed prospective studies and randomized controlled trials, is needed to verify these findings,” the researchers wrote. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.