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

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. METHODSThis 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. RESULTSIn 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 5 .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.

Update on long QT syndrome

“…These include avoidance of QT‐prolonging drugs (see below) and identification and correction of electrolyte abnormalities caused by diarrhea, vomiting, metabolic conditions or imbalanced diets for weight loss . The evidence that grapefruit juice prolongs the QT interval in healthy volunteers and patients with LQTS also suggests a role of “proarrhythmic food” …”

“…63 The evidence that grapefruit juice prolongs the QT interval in healthy volunteers and patients with LQTS also suggests a role of "proarrhythmic food". 64 Regarding sports participation, previous guidelines by the 36th In asymptomatic patients, the protective benefit of an ICD should be balanced against the risk of device-related complications and the influence of age and gender should be considered. For example, for a male with LQTS who has remained asymptomatic by the age of 25 years, the risk of ever developing an arrhythmia is very small even in the absence of therapy.…”

Congenital long QT syndrome: Should citric fruits be avoided? A case report of a cLQTS type 1 with unusual QTc prolongation with citric juices

“…Maximum QTc prolongation occurs at 4-5 h after the ingestion of grapefruit juice by normal individuals, being the mean QTc of 12.5 ms [6] to 14.0 ms [7]. In patients with cLQTS, mean QTc prolongation was 21.8 ms and a maximum of 48.5 ms was registered [7].…”

“…Different trials have confirmed that grapefruit juice prolongs the QTc in healthy individuals [6,7] and in patients with cLQTS [7]. The molecular basis of this QTc prolongation is due to the inhibition of HERG (also known as KCNH2, which is a potassium channel responsible for the rapid delayed rectifier current I Kr [2] of the phase 3 of the cardiac cells action potential) by flavonoids present on grapefruit, being the naringenin, morin, and hesperetin the three most potent inhibitors [6].…”

The Grapefruit Flavonoid Naringenin Inhibits Multiple Cardiac Ion Channels

“…Regarding grapefruit juice speci cally, Chorin et al (Chorin et al, 2019) recently established in a well powered randomized TQT study in healthy volunteers, that the length of the QT segment on the ECG corrected for heart rate (i.e. QTc) increased signi cantly as soon as three hours after drinking 1 liter of grapefruit juice.…”