What is the interaction between levothyroxine (thyroid hormone replacement medication) and grapefruit or grapefruit juice in patients with a history of hypothyroidism?

Grapefruit and Levothyroxine Interaction

Grapefruit juice may slightly delay levothyroxine absorption and reduce its bioavailability by approximately 9-13%, but this interaction is clinically minor and does not require avoiding grapefruit in most patients taking levothyroxine. 1, 2

Mechanism and Magnitude of Interaction

• Grapefruit juice delays the absorption of levothyroxine and reduces its bioavailability, as stated in the FDA drug label for levothyroxine 1
• The most rigorous study found that grapefruit juice decreased the maximal T4 concentration by only 11% (from 66.4 to 59.4 nmol/L) and reduced the area under the curve by 9-13% in the first 4-6 hours after levothyroxine ingestion 2
• The decrease in TSH levels 24 hours after levothyroxine ingestion was not altered by grapefruit juice, indicating minimal clinical impact on thyroid hormone regulation 2

Clinical Significance

• The clinical relevance of the grapefruit juice-levothyroxine interaction is likely to be small, as the effect on bioavailability is modest and does not significantly affect TSH suppression 2
• This interaction is far less clinically significant than other well-documented interactions with levothyroxine, such as calcium carbonate (which can cause marked malabsorption), iron supplements, or soybean flour 1, 3

Practical Management Recommendations

• Patients do not need to avoid grapefruit juice entirely when taking levothyroxine, as the interaction is minor 2
• For patients who consume grapefruit juice regularly and in large quantities (>200 mL three times daily), consider monitoring TSH levels to ensure therapeutic targets remain within the reference range of 0.5-4.5 mIU/L 4, 2
• If a patient's TSH becomes elevated while consuming large amounts of grapefruit juice, consider timing separation: take levothyroxine on an empty stomach 30-60 minutes before breakfast and consume grapefruit juice at a different time of day 4, 1
• More clinically important: ensure levothyroxine is taken consistently on an empty stomach, at least 4 hours apart from calcium, iron supplements, or antacids, which cause far more significant absorption problems 1, 3

Common Pitfalls to Avoid

• Do not overreact to this interaction by unnecessarily restricting grapefruit juice in patients with well-controlled hypothyroidism, as the effect is minimal compared to other dietary and medication interactions 2
• Focus monitoring efforts on more significant factors that affect levothyroxine requirements: weight changes, pregnancy, concomitant medications (especially calcium, iron, proton pump inhibitors), and adherence to taking levothyroxine on an empty stomach 4, 5
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses that suppress TSH completely—regular TSH monitoring every 6-12 months is far more important than worrying about grapefruit juice 4, 6