Kassis E, Fulder S, Khalil K, et al. Efficacy and safety assessments of Ferula assa-foetida L., traditionally used in Greco-Arab herbal medicine for enhancing male fertility, libido and erectile function. The Open Complementary Medicine Journal. 2009;1:102-109.  

Asafetida (Ferula assa-foetida) root has been used in ancient and modern Arabic traditional medicine as a spice, aphrodisiac, and for the treatment of impotence. Previous studies report digestive tonic, carminative, and hypolipidemic activities with the roots in animal studies or clinical settings. In this study, the authors investigate a combination of asafetida seed and root extracts known as Masculine™ (Antaki-laboratories; Kfar Cana, Israel) on erectile function and sperm count in vivo and in a clinical study. Also, the asafetida extracts were examined for potential toxicity, antioxidant activity, and vasodilation with in vitro and in vivo models.

Asafetida seeds and roots were procured from a Jerusalem medicinal plant market. Masculine consisted of an ethanol extract of the seeds and a 50% ethanol/water extract of the root in 310 mg tablets. Each tablet contained 98 mg of dried seed extract, 63 mg of dried root extract, 4.1 mg of vitamin E, and 144.9 mg of tricalcium phosphate.

The LD₅₀ dosage of 5 g/kg was determined by feeding rats increasing concentrations of seed and root extracts. The lactate dehydrogenase (LDH) assay was conducted with human fibroblasts to further assess toxicity (a higher concentration of LDH is indicative of cell membrane rupture). The authors found no significant differences in LDH concentration of cells incubated with 180 and 360 mg/ml of seed and root extracts for 24, 48, and 72 h in comparison to the control; however, the data show a time-dependent increase in LDH at the 360 mg/ml concentration.

To measure antioxidant activity, the asafetida extracts were tested in the thiobarbituric acid reactive substances (TBARS) assay with both rat liver and human sperm cells incubated with 0, 0.01, 0.05, 0.1, and 1 mg/ml of extracts. In rat liver cells, the extracts significantly reduced malondialdehyde (MDA), a product of lipid peroxidation, at 0.01 and 0.05 mg/ml as compared with the control: 0.017 ± 0.02 ng/mg protein and 0.013 ± 0.01 ng/mg protein vs. 0.27 ± 0.02 ng/mg protein (P<0.01 and P<0.001, respectively). [Editor's Note: The units given for this assay are ng/mg protein in the text versus nmol/mg protein in figures (2) and (3).] The other concentrations of extract tested, 0.1 and 1.0 mg/ml, also significantly decreased MDA in rat cells as compared with the control (P<0.05). In human sperm cells, 0.01 and 0.05 mg/ml of extract reduced MDA significantly as compared with the control: 0.31 ± 0.02 ng/mg protein and 0.16 ± 0.02 ng/mg protein vs. 0.52 ± 0.03 ng/mg protein (P<0.001 and P<0.0005, respectively).

To assess any vasodilation activity, asafetida extracts were incubated with 1 arterial ring containing epithelium and 1 without, both isolated from Sprague-Dawley rats. After incubation with the 1 mg/ml concentration, the ring with epithelium significantly lost tension from 800 ± 30 mg to 310 ± 20 mg (P<0.05), while the ring without epithelium lost less tension from 800 ± 30 mg to 640 ± 25 mg (P<0.05).   

This study also addressed the effect of oral treatment with Masculine on penile erection in rats. Two groups of rats (n=10) were used; 1 group was given 200 mg/kg of Masculine orally for 1 week, and on day 7, penile erections of both groups were counted hourly for 3 hours in response to the presence of female rats in heat in a nearby cage. During the first hour, the treated rats had significantly more erections than the control rats (19.1 ± 1.5 vs. 4.7 ± 1.7, respectively; P<0.05) and continued with significantly more erections throughout the time period investigated.

To clinically evaluate Masculine, either medically untreatable infertile (azoospermia) men (n=60), some with a history of normal fertility, or men suffering from erectile dysfunction and/or impotence (n=25) without a medically treatable cause were recruited. Patients were given 1 Masculine tablet daily for 3 months, and measurement of sperm counts of all patients and the sexual function of the patients with erectile dysfunction were taken at baseline and 3 months. In 10 of the infertile patients, the sperm count significantly increased from 0 ± 0 million/ml to 0.8 ± 0.1 million/ml (P<0.004), and sperm motility also significantly increased (P<0.007) after 3 months. No effect was observed in the other 50 infertile patients. Also, 15 of the 25 patients with erectile dysfunction reported "considerable improvements" in their libido and erectile function. Of the 15 patients in this group that were oligospermic (lower sperm count than normal), their sperm count significantly increased from 2.2 ± 0.1 million/ml to 2.8 ± 0.1 million/ml (P<0.0001), as well as sperm motility from 23.8 ± 1.5% to 43.2 ± 1.3% (P<0.0001) at 3 months of treatment. No adverse effects were reported.

The authors conclude that the LD₅₀ dosage and in vitro studies, along with the absence of adverse effects in animals and patients, point to the safety of Masculine and asafetida extracts. The data reported here are novel and require substantiation and confirmation. No placebo was used so the clinical part is a clinical observation only, and patients' improvement in libido and erections were subjective, though sperm counts were quantified and significantly changed. The authors suggest that the vasodilating activity of asafetida extracts is primarily endothelial-mediated, but do not offer any support from the literature. A more thorough clinical trial and more extensive in vitro experiments are necessary to confirm the activity of asafetida.