Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome

Heart Rhythm. 2019 Aug;16(8):1141-1148. doi: 10.1016/j.hrthm.2019.04.039. Epub 2019 May 8.

Abstract

Background: The list of medications linked to drug-induced long QT syndrome (LQTS) is diverse. It is possible that food products too have QT-prolonging potential.

Objective: We tested the effects of grapefruit juice on the QT interval with the methodology used by the pharmaceutical industry to test new drugs.

Methods: This was an open-label, randomized, crossover study with blinded outcome evaluation, a thorough QT study of grapefruit juice performed according to the Guidelines for the Clinical Evaluation of QT/QTc for Non-antiarrhythmic Drugs. Thirty healthy volunteers and 10 patients with congenital LQTS were studied. Healthy volunteers drank 2 L of grapefruit juice (in divided doses), or received 400 mg oral moxifloxacin, in a randomized crossover study. Patients with LQTS were tested with only grapefruit. Repeated baseline, off-drug, and on-drug (grapefruit or moxifloxacin) electrocardiograms were scanned and coded. QT measurements were done with electronic calipers.

Results: In comparison to off-drug electrocardiograms, grapefruit juice led to significant rate-corrected QT (QTc) prolongation. The absolute net QTc prolongation from grapefruit was 14.0 ms (95% confidence interval 6.2-21.7 ms; P < .001). The QT-prolonging effects of grapefruit in healthy volunteers were comparable with those of moxifloxacin. The QT-prolonging effects of grapefruit juice were greater in female patients and particularly marked in patients with LQTS (net QTc prolongation 21.8 ms; 95% confidence interval 3.4-35.3 ms; P = .034).

Conclusion: Grapefruit juice, at doses tested, prolongs the QT interval. The effect is significant in healthy volunteers, greater in female patients, and more so in patients with LQTS.

Trial registration: ClinicalTrials.gov NCT02680080.

Keywords: Adverse events; Drug-induced long QT syndrome; Proarrhythmia.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Citrus paradisi*
  • Cross-Over Studies
  • Electrocardiography / methods*
  • Female
  • Fruit and Vegetable Juices*
  • Healthy Volunteers
  • Heart Rate / physiology*
  • Humans
  • Long QT Syndrome / physiopathology
  • Long QT Syndrome / therapy*
  • Male
  • Middle Aged

Associated data

  • ClinicalTrials.gov/NCT02680080