Erectile dysfunction (ED) or impotence is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance [1
One of the oldest diseases known to mankind, ED affects 52% of 40- to 70-year-old men [2
] with estimates predicting the incidence to rise to over 320 million by the year 2025 [3
]. The earliest reports of medical therapies for ED are found in ancient medical literature prescribing the use of numerous herbs and natural ingredients for sexual rejuvenation and a healthy progeny. As sexual medicine evolved, introduction of intracavernous injection therapy followed by phosphodiesterase type-5 (PDE type-5) inhibitors revolutionized the treatment of ED. Despite the enormous success of pharmacological agents and a wide variety of treatment choices currently available, the ED sufferer continues to resort to natural alternatives or herbal supplements to regain his sexual vigor.
Clinicians on the other hand, do not wholeheartedly recommend herbal or alternative therapies, mainly due to a lack of adequate evidence from robustly designed scientific studies [4
]. In the absence of any regulatory obligations to undertake rigorous testing for safety and efficacy of dietary supplements [7
], there is no impetus for evaluation of herbal or dietary supplements before they are sold over-the-counter. Manufacturers base the advertising or labeling claims for such products on the testing of individual ingredients rather than the whole composition [8
]. There are also risks attendant upon self-medication and unmonitored use of these products [9
]. Evidence of contamination of herbal products with PDE type-5 inhibitors [10
] further prompts the need for companies to act responsibly and encourage third-party scientists to conduct efficacy and safety studies on natural products claiming therapeutic health benefits.
In the present study, we evaluated the safety and efficacy of a multi-herb formulation marketed as VigRx Plus (Leading Edge Herbals), created for enhancement of sexual health in men. Development of this product was based on the preliminary evaluation of a first generation product, VigRX, consisting of a proprietary blend of Panax ginsengSerenoa repensGingko bilobaCrataegus laevigataPtychopetalum olacoidesErythroxylum catuabaCuscuta chinensis
, and Epimedium sagittatum
extract. In two different studies in male Sprague–Dawley rats, VigRX was shown to engender a marked improvement in sexual behaviour including decreased intromission and ejaculation latencies, and increased intromission, ejaculation and mounting frequencies [11
]. In the same study, assays for pharmaceutical adulteration found that VigRX did not contain any detectable levels of known PDE-5 inhibitors including sildenafil, tadalafil, vardenafil or related analogues. In vitro
assays also determined that VigRX is able to inhibit the Rho-kinase. Rho-kinase is an enzyme that plays an important role in maintaining the flaccid state of the penis through cavernosal vasoconstriction [12
] and is being increasingly considered as emerging target for the treatment of erectile dysfunction [13
]. VigRX, however, exhibited a relatively high inhibition concentration in the Rho-kinase inhibition assay, indicating that a large dose would be necessary to achieve similar results in a living system. Hence, three more ingredients Tribulus terrestrisTurnera diffusa
and Bioperine® (piperine) were added to the formulation. The resulting new formulation, named VigRX Plus (Table ), was evaluated for its aphrodisiac properties in male albino Wistar rats. Treatment with VigRX Plus at the dose of 450
mg/kg showed a significant increase in ejaculation frequency on day 7 and a non-significant increase on day 14 with a marginal increase in testosterone concentration in serum and number of spermatogonia cells in seminiferous tubules of testes (Unpublished data;Available uponrequest).
An acute oral toxicity study of VigRX Plus tablet blend observed no lethality, nor adverse effects at single oral doses up to 4,000
mg/kg in female rats (Unpublished data,Available uponrequest)
With the accrued preclinical evidence, VigRx Plus demonstrated potential as a novel agent for management of ED. It was thus imperative to evaluate its safety and efficacy in humans.