Reference
Ambiye VR, Langade D, Dongre S, Aptikar P, Kulkarni M, Dongre A. Clinical evaluation of the spermatogenic activity of the root extract of Ashwagandha (Withania somnifera) in oligospermic males: a pilot study. Evid Based Complement Alternat Med. 2013;2013:571420.
Design
Double-blind, randomized, placebo-controlled parallel-group pilot study
Participants
68 healthy men, ages 22–40 years old with male factor infertility were assessed. Of these participants, 46 were included after being deemed eligible for inclusion. Male factor infertility was defined by a sperm concentration between 5 and 20 million/mL, total motility of 10%–30% with forward motility <15%, and abnormal morphological forms >70%. All participants had a history of regular intercourse with a female partner. Participants were randomly assigned to 1 of 2 groups. Participants were excluded if they had a history of erectile dysfunction, congenital anomalies, uncontrolled diabetes, cryptorchidism, varicocele, genital tract surgery, or testicular hypertrophy.
Study Medication and Treatment Protocol
Twenty-one men in the treatment group received 225 mg of encapsulated Ashwagandha root by mouth 3 times daily for 12 weeks, while 25 men in the control group received a placebo capsule by mouth 3 times daily. The participants were instructed not to take any other medications or supplements that could affect spermatogenesis during the study. The Ashwagandha root, known as KSM-66, had been extracted, concentrated, and standardized to contain at least 5% withanolides by Ixoreal Biomed Private Ltd in Hyderabad, India.
Primary Outcome Measures
A semen analysis was performed to assess changes in sperm concentration, motility, and morphology at baseline, after 30 days of treatment, and again after 90 days of treatment. Serum testosterone and luteinizing hormone (LH) were assessed at baseline and after 90 days of treatment.
When comparing semen parameters at baseline and after the 90-day treatment phase, average sperm concentration rose corresponding to a 167% increase in sperm concentration in men treated with Ashwagandha root.
Key Findings
When comparing semen parameters at baseline and after the 90-day treatment phase, average sperm concentration rose from 9.6 + 4.4 x 106/mL to 25.6 + 8.6 x 106/mL, corresponding to a 167% (P<0.0001) increase in sperm concentration in men treated with Ashwagandha root. Average semen volume increased from 1.74 + 0.58 mL to 2.76 + 0.60 mL, corresponding to a 53% increase in semen volume in men treated with Ashwagandha root for 90 days (P<0.0001). Average sperm motility increased from 18.6 + 6.1% to 29.2 + 6.3%, corresponding to a 57% increase in sperm motility after 90 days of treatment with Ashwagandha root. Compared to baseline, serum testosterone increased by 17% (P<0.01) and LH increased by 34% (P<0.02). No adverse events or side effects were reported by any of the participants.
Practice Implications
Infertility, which is diagnosed when a couple fails to conceive after 12 months of unprotected intercourse, affects 15% of all couples; 50% of these cases are attributed to male factor infertility. Evidence suggests that male fertility is declining, with an estimated decline in mean sperm count of approximately 2% per year, according to one study.1 Male infertility is idiopathic in 30%, meaning standard clinical and laboratory evaluations do not reveal a cause.2 Hormonal imbalances, endocrine disruptors, and poor lifestyle choices can all play a role in male infertility. In addition, oxidative stress mediated by reactive oxygen species (ROS) is being recognized more commonly as a causative factor in male infertility.3,4 This is because mature spermatozoa, encased in a polyunsaturated lipid membrane, are vulnerable to the effects of ROS, which at high doses can impair spermatogenesis and decrease sperm quality, thereby decreasing sperm motility and morphology.5–7 Sperm count and quality are also affected by hormones of the hypothalamic-pituatary-gonadal (HPG) axis whereby the hypothalamus produces gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH stimulate spermatogenesis and testosterone secretion by acting on the Sertoli cells and Leydig cells, respectively.8,9 Spermatogenesis is regulated by a complex interplay of FSH, LH, and intratesticular testosterone. Disruptions in the HPG axis have been shown to be detrimental to semen parameters.10,11
Reproductive endocrinologist treat men with abnormal semen parameters with injectable medications such as recombinant FSH, human chorionic gonadotropin (hCG), hormone human menopausal gonadotropin (hMG), or gonadotropin-releasing hormone (GnRH). Clomiphene citrate, an estrogen receptor antagonist, is an oral medication used to stimulate gonadotropin release from the pituitary. However these options are expensive, not widely accessible, can take up several months to yield benefit and are not without risk.12 Given these shortcomings, naturopathic doctors are well positioned to offer their patients a more holistic approach to improving male reproductive health. Evidence-based natural medicines for improving male infertility due to oxidative stress have been discussed previously in Natural Medicine Journal here and here.
When clinicians determine that dysregulation of the HPG is contributing to male infertility, Ashwagandha root can be recommended to improve semen parameters. Ashwagandha, a medicinal plant whose name means “horse’s smell” in Sanskrit,13 has been used for thousands of years to treat hypogonadism, low libido, and male infertility.14,15 It is used in Ayurvedic medicine as a rasayana (or rejuvenating) tonic that restores strength from within. The results of this study are consistent with a prior study demonstrating that Ashwagandha improves sperm parameters in infertile men with hypogonadism.16 While this study lacked long-term follow-up and evaluation of pregnancy rates with Ashwagandha treatment, the statistically significant improvement in semen parameters, lack of adverse reactions and side effects, as well as relative affordability in comparison to assisted reproductive techniques, should warrant consideration of Ashwagandha root as part of a naturopathic approach to treating male infertility, particularly when low testosterone or HPG dysregulation are contributory.