Reviewed: Gupta A, Mahdi AA, Shukla KK, et al. Efficacy of Withania somnifera on seminal plasma metabolites of infertile males: a proton NMR study at 800 MHz. J Ethnopharmacol. 2013;149(1):208-214.

Infertility affects between 10 to 15% of couples worldwide.¹ In traditional Indian systems of medicine, ashwagandha (Withania somnifera, Solanaceae) root is a highly regarded tonic and adaptogenic herb, and it also is used to treat impotence and infertility. There is some experimental evidence that ashwagandha root improves semen quality and decreases spermatorrhea by regulating reproductive hormone levels and oxidative stress.2,3 This study evaluated the effects of ashwagandha root powder on seminal plasma metabolites, enzymes, and hormones in infertile men by using high-resolution proton nuclear magnetic resonance (NMR) spectroscopy.

Ashwagandha root contains withanosides, essential and non-essential fatty acids, amino acids, sterols, catecholamines, aromatic alcohols and acids, gamma-aminobutyric acid, and glycerol. The roots for this study (obtained from the Central Council for Research in Unani Medicine; New Delhi, India) were dried and ground into a fine powder.

One hundred and eighty infertile male subjects aged 22 to 45 years recruited from the infertility clinic at King George’s Medical University in Lucknow, India — plus an additional 50 healthy, age-matched men — were included in the study and subdivided into the following groups (experimental subjects: n=180; control subjects: n=50):

Normozoospermic (NZ; n=60) men who had a normal semen profile (>20 x 106 spermatozoa/mL, >40% motility, and >40% normal morphology) and infertility of unknown etiology;

Oligozoospermic (OZ; n=60) men who had a sperm concentration <20 x 106/mL, >40% motility, and >40% normal morphology;

Asthenozoospermic (AZ; n=60) men who had a sperm concentration >20 x 106/mL, but <40% motility, and >40% normal morphology; and

An additional 50 healthy, age-matched men (>20 x 106 spermatozoa/mL, >40% motility, and >40% normal morphology) who served as controls (CZ; n=50).

The subjects in the NZ, OZ, and AZ groups were prescribed ashwagandha root powder (five grams daily taken orally with milk in a single dose; qualitative analysis of the roots not provided) for three months. Semen and blood samples were collected at baseline and after three months of treatment.

Seminal plasma samples were analyzed using proton NMR spectroscopy to determine concentrations of the metabolites lactate, alanine, glutamate, glutamine, citrate, lysine, choline, glycerophosphocholine (GPC), glycine, tyrosine, histidine, phenylalanine, and uridine. Sperm concentration, motility, lipid peroxide (LPO), enzyme, and hormone levels also were measured.

The concentrations of lysine, choline, glutamine, glycine, tyrosine, and uridine did not change significantly in any group post-treatment. Compared with baseline values, alanine, glutamate, citrate, GPC, and histidine increased significantly in the NZ, OZ, and AZ groups after three months of treatment. Phenylalanine concentrations decreased significantly compared with baseline values in NZ and OZ groups, while lactate concentrations showed significant differences compared with baseline values in OZ and AZ groups. Sperm concentration, motility, and LPO levels also improved significantly in these groups compared with baseline values.

According to the authors, this is the first study to analyze metabolite concentrations using an 800 MHz NMR spectrometer to measure levels of the enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and isocitrate dehydrogenase in the seminal plasma of infertile males in an attempt to elucidate the physiological effects of ashwagandha. Enzyme levels increased significantly in all groups of infertile subjects post-treatment compared with baseline, except for LDH in the NZ group.

Compared with baseline, there was a significant increase in luteinizing hormone and testosterone in all groups post-treatment. Follicle-stimulating hormone and prolactin levels decreased in all three groups of infertile subjects but were significant only in OZ and AZ groups.

The authors note that “[a]berrations of endogenous metabolites, enzymatic activities, and hormone levels commonly precede the onset of infertility.” An important finding in this study is that oral intake of ashwagandha for three months by infertile men resulted in substantial enhancement of seminal plasma metabolic profiles and improvements in enzymatic, hormonal, and clinical parameters (sperm concentration, motility, and LPO). The authors conclude that ashwagandha “can be used as an alternative empirical therapy for the treatment and clinical management of male infertility.”

However, this study could have benefitted from the inclusion of a placebo group, randomization, and both baseline and endpoint measurements of control group blood and semen values (the authors procured and evaluated only one blood and semen sample for each control group member during the study). Also, the authors could have provided demographic information of the subjects involved in the study.

—Shari Henson

References

1. Callister LC. Global infertility: are we caring yet? MCN Am J Matern Child Nurs. 2010;35(3):174.
2. Mahdi AA, Shukla KK, Ahmad MK, et al. Withania somnifera improves semen quality in stress-related male fertility. Evid Based Complement Alternat Med. 2011;2011:576962. doi: 10.1093/ecam/nep138.
3. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010;94(3):989-996.