Men taking a dietary supplement marketed as a sexual function aid had a significant increase in cardiac QTc interval that persisted for five hours after a single dose, a small study of healthy volunteers showed.
The mean QTc interval increased by 32 msec three hours after a dose of Enzyte and by 37 msec after five hours, compared with placebo. Differences from placebo were similar in magnitude whether QTc was determined by the Bazett or Framingham correction formula.
“Because most male patients are embarrassed to report erectile dysfunction, the use of QTc prolonging supplements, such as Enzyte, is likely to be underreported to healthcare providers,” Mark Phillips, DO, of the Chicago College of Osteopathic Medicine, and coauthors reported in a letter in the Aug. 9/23 issue of Archives of Internal Medicine.
“This creates a relatively anonymous patient population at an elevated risk for drug-induced sudden death.”
The magnitude of the changes in QTc is consistent with previous evidence indicating that an increase of 30 to 60 msec may predispose a person to torsades de pointes, they added.
Enzyte is marketed as a natural approach to “male enhancement.” The product is a “multicomponent preparation marketed to consumers without stringent regulatory oversight or premarketing evaluation of pharmacokinetics, pharmacodynamic, or drug interaction studies, including thorough QT and corrected QT studies to assess arrhythmic risk,” the authors wrote.
Ingredients in the product include Gingko biloba, horny goat weed extract, Korean ginseng, L-arginine, Tribulus terrestris extract, niacin, zinc, and copper.
Phillips and coauthors reported findings from a randomized, blinded, crossover study of nine healthy young men. The study group had a mean age of 28.7, mean body mass index of 26, and no risk factors for torsades de pointes or use of drugs that posed a risk of interaction.
Each participant completed four evaluation sessions. During one session, the participants received a placebo, and in the other sessions they received one half, one, or two tablets of the supplement known as Enzyte.
The primary outcome was the difference in maximum postdosing QTc interval at one, three, and five hours between the placebo period and each of the active-dosing periods. Maximum postdosing QTc interval was defined as the longest QTc interval from all evaluable ECG leads during each of the three active-dosing periods.
Investigators calculated QTc interval by means of the Bazett formula for the primary analysis and by the Framingham linear corrected formula as a secondary analysis.
For the placebo dosing period using the Bazett formula, QTc interval averaged 385 msec at baseline, 384 msec at one hour, 380 msec at three hours, and 388 msec at five hours. Averages (in msec) for baseline followed by the three active dosing periods were as follows:
The authors concluded that “clinicians should advise patients to refrain from using Enzyte until more information is known.”
The study’s implications for practicing physicians are not entirely clear, given the lack of knowledge about which patients might be taking Enzyte and how they might differ from healthy volunteers, Paul Shekelle, MD, of RAND Health in Santa Monica, Calif., wrote in a commentary. Moreover, the study lacked sufficient follow-up to assess potential adverse effects.
Nonetheless, the findings “must be taken as a signal that there is something potentially lurking beyond our current eyesight regarding the safety of Enzyte,” Shekelle wrote. “Their conclusion that clinicians should advise their patients to avoid this dietary supplement until more evidence is available seems justified and prudent.”
Shekelle noted that according to a National Center for Complementary and Alternative Medicine report, Americans spent $14.8 billion on “nonvitamin, non-mineral natural products” in 2007. But these dietary supplements raise safety concerns, he added; a report from the Government Accountability Office found that 92% of a sample of herbal supplements contained trace amounts of lead, and 80% had at least one other contaminant, such as mercury.
source: Archives of Internal Medicine