Do Studies Evaluating QT/QTc Interval Prolongation with Dietary Supplements Meet FDA Standards: A Systematic Review.

PURPOSE: Dietary supplement use is continuously increasing, but the safety evaluation of these products remains partial. While dietary supplements have no mandate for assessing cardiovascular safety, all new drug entities (NDE) are required to undergo a thorough QT/corrected QT (QTc) assessment to determine their propensity to impact cardiac repolarization. Independent investigators and manufacturers of dietary supplements voluntarily initiate safety studies; however, the quality of these studies is controversial. We sought to compare studies evaluating the QT/QTc effects of dietary supplements based on the International Conference of Harmonization (ICH)-E14 recommendations for NDE. CASE SUMMARY: Twenty-six published dietary supplement studies assessed QT/QTc interval prolongation. Sample sizes ranged from nine subjects to 206 among the 15 crossover studies, six parallel design studies, and five observational studies. A plan to account for electrocardiogram (ECG) morphological abnormalities was included in 10 studies, and two studies reported cardiovascular adverse events. Eight studies found a significant change in QT/QTc intervals. CONCLUSIONS: The majority of studies included in this review contained many of the critical elements recommended by the ICH E14, which includes the U.S. Food and Drug Administration guidance document for QT/QTc interval assessment. Compared with the thorough QT (TQT) standards, studies are typically well performed but can be bolstered by some study design changes. More than 30% of the included studies showed some degree of ECG changes, suggesting the need for continued cardiovascular safety assessment of dietary supplements.

Electrocardiographic and blood pressure effects of energy drinks and Panax ginseng in healthy volunteers: A randomized clinical trial.

BACKGROUND: Energy drink usage has been linked to emergency room visits and deaths. The objective of the study is to assess the electrocardiographic and blood pressure effects of energy drinks, Panax ginseng and placebo in healthy individuals. METHODS: This was a randomized, double blinded, placebo controlled, crossover study. Young healthy volunteers with no comorbid conditions consumed 32oz of an energy drink, control drink with 800mg of Panax ginseng or matching placebo-control drink over 45min. Primary endpoints were QTc interval and systolic blood pressure. Secondary endpoints included QT interval, PR interval, QRS duration, heart rate, and diastolic blood pressure. All endpoints were assessed at baseline, 1, 2, 3.5, and 5.5h. RESULTS: A significant increase in QTc interval 2h post energy drink consumption was evident when compared to placebo (3.37±10.7ms and -3.19±11.8ms respectively; p=0.030). Similarly, systolic blood pressure 2h post energy drink consumption increased when compared to placebo (2.00±6.37mmHg and -2.67±5.83mmHg respectively; p=0.014). The PR interval significantly reduced over a 2h period post energy drink use in a clinically non-meaningful manner. Heart rate at 2h was not significantly higher in the energy drink group when compared to others. The QT interval, QRS interval and diastolic blood pressure were not impacted at any time point. CONCLUSIONS: Certain energy drinks consumed at a high volume significantly increase the QTc interval and systolic blood pressure by over 6ms and 4mmHg respectively. Panax ginseng does not have a significant impact on ECG or blood pressure parameters.