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

  • 2019-08
  • Heart rhythm 16(8)
    • Ehud Chorin
    • Aviram Hochstadt
    • Yoav Granot
    • Shafik Khoury
    • Arie Lorin Schwartz
    • Gilad Margolis
    • Rami Barashi
    • Dana Viskin
    • Eihab Ghantous
    • Michael Schnapper
    • Tal Mekori
    • Dana Fourey
    • Milton Ernesto Guevara-Valdivia
    • Manlio F Marquez
    • David Zeltzer
    • Raphael Rosso
    • Sami Viskin

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 10
Population
30 healthy volunteers and 10 patients with congenital LQTS
Methods
Open-label, randomized, crossover study with blinded outcome evaluation; healthy volunteers drank 2 L grapefruit juice (in divided doses) or received 400 mg oral moxifloxacin; LQTS patients tested with only grapefruit
Blinding
Open-label
Funding
Unclear

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.

Research Insights

  • Grapefruit→Prolonged QT Interval

    The absolute net QTc prolongation from grapefruit was 14.0 ms (95% confidence interval 6.2-21.7 ms; P < .001).

    Effect
    Harmful
    Effect size
    Moderate
    Dose
    2 L of grapefruit juice (in divided doses)
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