Is levothyroxine (T4) absorbed in the mouth?

Levothyroxine Oral Absorption

Levothyroxine is NOT absorbed in the mouth—it is absorbed exclusively in the small intestine, primarily in the jejunum and ileum. 1

Site of Absorption

• Levothyroxine absorption occurs throughout the small intestine, with the jejunum and ileum being the primary sites of absorption, while duodenal absorption rates are lower. 1

• The time interval between oral ingestion and plasma appearance of levothyroxine makes gastric (stomach) absorption extremely unlikely, as the drug must pass through the stomach before reaching the small intestine where actual absorption occurs. 1

• No evidence exists for buccal (mouth) or sublingual absorption of standard levothyroxine formulations—the drug must reach the small intestine to enter the bloodstream. 1, 2

Role of the Stomach (But Not Absorption)

• The stomach plays a critical prerequisite role for efficient absorption, but does NOT absorb levothyroxine itself—gastric processes dissolve the tablet and prepare the active ingredient for absorption downstream in the small intestine. 1

• Gastric pH, volume, viscosity, and emptying time are the most important limiting factors that determine how efficiently levothyroxine will be absorbed once it reaches the small intestine. 1

• Conditions that impair gastric function increase levothyroxine requirements because they interfere with tablet dissolution and preparation for intestinal absorption—these include Helicobacter pylori infection, chronic atrophic gastritis, gastroparesis, and proton pump inhibitor use. 1, 3

Clinical Implications

• Patients should take levothyroxine on an empty stomach, 30-60 minutes before breakfast, to maximize gastric emptying and subsequent small intestinal absorption—this timing recommendation exists because food delays gastric emptying and interferes with dissolution, not because of any oral cavity absorption. 4, 3

• Switching levothyroxine administration from before breakfast to before dinner reduces therapeutic efficacy, resulting in a mean TSH increase of 1.47 µIU/mL and T4 decrease of 0.35 µg/dL, demonstrating that absorption timing matters because of gastric and intestinal factors, not oral absorption. 4

• Liquid levothyroxine formulations (oral solutions) may improve absorption in patients with gastric disorders like gastroparesis or small intestinal bacterial overgrowth (SIBO), but these still require passage through the stomach and absorption in the small intestine—they are not absorbed in the mouth. 5

Common Pitfall to Avoid

• Do not assume that holding levothyroxine under the tongue or in the mouth will enhance absorption—there is no evidence for buccal or sublingual absorption of standard levothyroxine preparations, and the drug must reach the small intestine to be absorbed. 1, 2, 3