Safety and efficacy of daily Revactin(®) in men with erectile dysfunction: a 3-month pilot study

BACKGROUND: The earliest sign of an ongoing change in a man’s erectile function (EF) is the increase in his refractory period. This is due to the onset of an aging related apoptosis of the corporal smooth muscle cells (CSMC) as a result of oxidative stress (ROS) within the CSMC itself. In response, the CSMC begin to upregulate the inducible nitric oxide synthase (iNOS) enzyme presumably to achieve high levels of nitric oxide (NO) used to combat ROS. Treatment of aged rats for 2 months with the nutraceutical Revactin(®), known to stimulate the iNOS-NO-cGMP pathway in CSMC, resulted in (I) an increase in CSMC content with a decrease in corporal fibrosis, (II) decrease in systemic ROS, and (III) improvement in EF. To determine whether Revactin(®) could be used in the clinical setting, a pilot safety study was conducted. METHODS: Fifty-four middle aged men (mean age 57.8±10.7; range, 33–77 years) were recruited for this safety study. Patients were given Revactin(®) twice daily (total daily dose of 500 mg of ginger root, muira puama, and Paullinia cupana and 1,600 mg of L-citrulline) and were asked to complete the IIEF-15 questionnaire [domains: EF, orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), overall satisfaction (OS)] at baseline (B), 1 month (M1), 2 months (M2) and 3 months (M3) and report any side effects. Those on erectogenic medications at B were requested to stop taking them during the trial. Data were analyzed using Wilcoxon paired test and Friedman rank test for trend. RESULTS: Revactin(®) was safe with only 5 patients reporting treatment side effects (e.g., dyspepsia, heartburn, migraine) and none considered severe. For those who stayed on the regimen (M1 =32; M2 =22; M3 =16), there was an increase in median domain scores for EF, OF, SD, IS, and OS over 3 months compared to baseline median scores but statistical significance was found only in the EF, IS, and OS median domain scores. Trend analysis indicated significant trend in EF, OS & IS (P<0.05). For the EF domain, the median scores were: M1 =21, M2 =22, M3 =19 relative to the B =16, 15.5, and 14.5, respectively (P<0.05). Overall, approximately 50% of the patients reported a significant improvement in EF (P<0.05). The major reason for trial discontinuation (M1 =22, M2 =9 and M3 =6) was non-compliance with pro-erectile medications. CONCLUSIONS: Revactin(®), a combination of 3 nutraceuticals packaged with L-citrulline, appears to have the same excellent safety profile known for each of its individual four components. The early improvement in EF seen in about 50% of these patients may be due to the elevated levels of cGMP produced via this iNOS-cGMP pathway. Further longitudinal studies with Revactin(®) appear warranted.