Clinical Studies

A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root in reducing stress and anxiety in adults. Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). Indian journal of psychological medicine, 34(3), 255.

Results: The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported.

Conclusion: The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual’s resistance towards stress and thereby improves self-assessed quality of life.

Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study Ambiye, V. R., Langade, D., Dongre, S., Aptikar, P., Kulkarni, M., & Dongre, A. (2013).  Evidence-Based Complementary and Alternative Medicine, 2013.

Results: There was a 167% increase in sperm count (9.59 ± 4.37 × 106/mL to 25.61 ± 8.6 × 106/mL; ), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; ), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; ) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum testosterone levels with the Ashwagandha treatment as compared to the placebo (p<0.001).

Conclusion: The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility.

Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults Choudhary, B., Shetty, A., & Langade, D. G. (2015). Ayu, 36(1), 63.

Results: There was a greater increase from baseline (P < 0.0001) in the mean VO2 max with KSM-66 Ashwagandha (n = 24) compared to placebo (n = 25) at 8 weeks (4.91 and 1.42, respectively) and at 12 weeks (5.67 and 1.86 respectively). The QOL scores for all subdomains significantly improved to a greater extent in the Ashwagandha group at 12 weeks compared to placebo (P < 0.05).

Conclusion: The findings suggest that Ashwagandha root extract enhances the cardiorespiratory endurance and improves QOL in healthy athletic adults.

Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial Wankhede, S., Langade, D., Joshi, K., Sinha, S. R., & Bhattacharyya, S. (2015). Journal of the International Society of Sports Nutrition, 12(1), 43.

Results: Compared to the placebo subjects, the group treated with ashwagandha had significantly greater increases in muscle strength on the bench-press exercise (Placebo: 26.4 kg, 95 % CI, 19.5, 33.3 vs. Ashwagandha: 46.0 kg, 95 % CI 36.6, 55.5; p = 0.001) and the leg-extension exercise (Placebo: 9.8 kg, 95 % CI, 7.2,12.3 vs. Ashwagandha: 14.5 kg, 95 % CI, 10.8,18.2; p = 0.04), and significantly greater muscle size increase at the arms (Placebo: 5.3 cm2, 95 % CI, 3.3,7.2 vs. Ashwagandha: 8.6 cm2, 95 % CI, 6.9,10.8; p = 0.01) and chest (Placebo: 1.4 cm, 95 % CI, 0.8, 2.0 vs. Ashwagandha: 3.3 cm, 95 % CI, 2.6, 4.1; p < 0.001). Compared to the placebo subjects, the subjects receiving ashwagandha also had significantly greater reduction of exercise-induced muscle damage as indicated by the stabilization of serum creatine kinase (Placebo: 1307.5 U/L, 95 % CI, 1202.8, 1412.1, vs. Ashwagandha: 1462.6 U/L, 95 % CI, 1366.2, 1559.1; p = 0.03), significantly greater increase in testosterone level (Placebo: 18.0 ng/dL, 95 % CI, -15.8, 51.8 vs. Ashwagandha: 96.2 ng/dL, 95 % CI, 54.7, 137.5; p = 0.004), and a significantly greater decrease in body fat percentage (Placebo: 1.5 %, 95 % CI, 0.4 %, 2.6 % vs. Ashwagandha: 3.5 %, 95 % CI, 2.0 %, 4.9 %; p = 0.03).

Conclusion: This study reports that ashwagandha supplementation is associated with significant increases in muscle mass and strength and suggests that ashwagandha supplementation may be useful in conjunction with a resistance training program.

Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study Dongre, S., Langade, D., & Bhattacharyya, S. (2015). BioMed research international, 2015.

Results: The analysis indicates that treatment with HCARE leads to significantly higher improvement, relative to placebo, in the FSFI Total score (p < 0.001), FSFI domain score for “arousal” (p < 0.001), “lubrication” (p < 0.001), “orgasm” (p = 0.004), and “satisfaction” (p < 0.001), and also FSDS score (p < 0.001) and the number of successful sexual encounters (p < 0.001) at the endof the treatment.

Conclusion: This study demonstrated that oral administration of HCARE may improve sexual function in healthy women.

Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial Choudhary, D., Bhattacharyya, S., & Joshi, K. (2017). Journal of evidence-based complementary & alternative medicine, 22(1), 96-106.

Results: KSM-66 Ashwagandha caused significant reduction in Perceived Stress among the subjects. At the end of the study, KSM-66 Ashwagandha produced a 32.74% reduction in PSS scores from the baseline compared to placebo group. KSM-66 Ashwagandha reduced desire or cravings for food in the study subjects. The FCQ scores for Planning, Positive and Negative reinforcement, Lack of control, Emotion and Environment domains were reduced significantly (P < 0.05) in the Ashwagandha supplemented subjects. A statistically significant (P < 0.05) decrease of 22.2% was observed in serum cortisol (a stress hormone) levels as a result of KSM-66 Ashwagandha supplementation compared to placebo group. KSM-66 Ashwagandha supplementation resulted in a 3.0% and 2.9% reduction in bodyweight (P < 0.05) and BMI (P < 0.05) respectively. Supplementation with KSM-66 Ashwagandha resulted in a significant (P < 0.05) increase in OHQ scores and a significant (P < 0.05) reduction in TFEQ scores for ‘Uncontrolled’ and ‘Emotional Eating behavior’ compared to placebo group.

Conclusion: The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.

Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions Choudhary, D., Bhattacharyya, S., & Bose, S. (2017). Journal of Dietary Supplements, 1-14. Chicago

Results: After eight weeks of study, the ashwagandha treatment group demonstrated significant improvements compared with the placebo group in both immediate and general memory, as evidenced by Wechsler Memory Scale III subtest scores for logical memory I (p = 0.007), verbal paired associates I (p = 0.042), faces I (p = 0.020), family pictures I (p = 0.006), logical memory II (p = 0.006), verbal paired associates II (p = 0.031), faces II (p = 0.014), and family pictures II (p = 0.006). The treatment group also demonstrated significantly greater improvement in executive function, sustained attention, and information-processing speed as indicated by scores on the Eriksen Flanker task (p = 0.002), Wisconsin Card Sort test (p = 0.014), Trail-Making test part A (p = 0.006), and the Mackworth Clock test (p = 0.009).

Conclusion: Ashwagandha may be effective in enhancing both immediate and general memory in people with MCI as well as improving executive function, attention, and information processing speed.

Withania somnifera root extract extends lifespan of Caenorhabditis elegans Kumar, R., Gupta, K., Saharia, K., Pradhan, D., & Subramaniam, J. R. (2013). Annals of neurosciences, 20(1), 13.

Results: Strangely, while there was no effect on the wild type worms, the mutant for the human nicotinic acetylcholine receptor, nAchR, α7 equivalent, acr-16, showed around ~20% lifespan extension when treated with PI-RE.

Conclusion: Ashwagandha extends the lifespan of C. elegans.

Withania somnifera Root Extract Enhances Telomerase Activity in the Human HeLa Cell Line Raguraman, V., & Subramaniam, J. R. (2016). Advances in Bioscience and Biotechnology, 7(04), 199.

Results: It has been observed that, KSM-66 Ashwagandha increased telomerase activity through TRAP assay, with highest enhancement of ~45% at 10-50μg concentration.

Conclusion: Ashwagandha root extract has the anti-aging inducing potential

Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. Sharma, A. K., Basu, I., & Singh, S. (2017).The Journal of Alternative and Complementary Medicine.

Results: A total of four subjects (two from each group) withdrew their consent before the second visit. Eight weeks of treatment with ashwagandha improved serum TSH (p < 0.001), T3 (p = 0.0031), and T4 (p = 0.0096) levels significantly compared to placebo. Ashwagandha treatment effectively normalized the serum thyroid indices during the 8-week treatment period in a significant manner (time-effects: TSH [p < 0.001], T3 [p < 0.001], and T4 [p < 0.001]). Four subjects (8%) (ashwagandha: 1[4%]; Placebo: 3[12%]) out of 50 reported few mild and temporary adverse effects during this study.

Conclusion: Treatment with ashwagandha may be beneficial for normalizing thyroid indices in subclinical hypothyroid patients.

Efficacy and Safety of Ashwagandha ( Withania somnifera) Root Extract in Insomnia and Anxiety: A Double – blind, Randomized, Placebo-controlled study. Langade, D., Kanchi, S., Salve, J., Debnath, K., & Ambegaokar, D (2019). Cureus, 11(9), e5797.

Results: Two patients, one from each group, did not complete study and the per-protocol dataset (n = 58) included 29 and 19 patients from test and placebo, respectively. The baseline parameters were similar in the two groups at baseline. The sleep onset latency was improved in both test and placebo at five and 10 weeks. However, the SOL was significantly shorter (p, 0.019) after 10 weeks with test [29.00 (7.14)] compared to placebo [33.94 (7.65)]. Also, significant improvement in SE scores was observed with Ashwagandha which was 75.63 (2.70) for test at the baseline and increased to 83.48 (2.83) after 10 weeks, whereas for placebo the SE scores changed from 75.14 (3.73) at baseline to 79.68 (3.59) after 10 weeks. Similarly, significant improvement in sleep quality was observed with test compared to placebo (p, 0.002). Significant improvement was observed in all other sleep parameters, i.e., SOL, SE, PSQI and anxiety (HAM-A scores) with Ashwagandha root extract treatment for 10 weeks.

Conclusion: Ashwagandha root extract is a natural compound with sleep-inducing potential, well tolerated and improves sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. It could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but need further large-scale studies.

Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study. Kelgane, S. B., Salve, J., Sampara, P., & Debnath, K. (2020)l. Cureus, 12(2), e7083.

Results: Statistically significant (P<0.0001) improvement was observed in the Ashwagandha treatment group compared to the placebo. The mean (SD) total score of WHOQOL-BREF improved from 140.53 (8.25) at the baseline to 161.84(9.32) at the end of the study. The individual domain scores were also improved. At baseline, the sleep quality and the mental alertness on rising were comparatively low in both the groups. However, upon intervention, a significant increase in the quality of sleep (P<0.0001) and mental alertness (P<0.034) was observed in the Ashwagandha treatment group when compared to the placebo group. Overall improvement was observed for the general wellbeing, sleep quality, and mental alertness in the study population. The experimental group population displayed good tolerability to the test product and it was reported as safe and beneficial by the study participants.

Conclusion: The study outcomes suggest that Ashwagandha root extract was efficient in improving the QoL, sleep quality, and mental alertness as self-assessed by the elderly participants. The recommended dose used in this study could be effective for the elderly population.

Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: A double-blind, randomized, parallel group, placebo-controlled study. Langade, D., Thakare, V., Kanchi, S., & Kelgane, S. (2020). Journal of Ethnopharmacology: 264:113276.

Results: At the end of the 8-week study, Ashwagandha root extract supplemented groups demonstrated a significant improvement in the sleep parameters in both healthy and insomnia subjects. The improvement was found more significant in insomnia subjects compared to healthy subjects. The repeat measure analysis of variance (ANOVA) confirmed the significant improvement in SOL (p = 0.013), HAM-A outcomes (p < 0.05), mental alertness (p = 0.01), and sleep quality (p < 0.05) of the insomnia patients. A two-way ANOVA was used to confirm these outcomes that denote Sleep Onset Latency (p < 0.0001) and Sleep Efficiency (p < 0.0001) as the most improved parameters, followed by Total Sleep Time (p < 0.002) and Wake After Sleep Onset (p < 0.040). After 8-weeks of study, there was a significant decrease in the mean score of mental alertness on rising in both the arms in the Ashwagandha supplemented group compared to the placebo group. All these parameters, SOL, TST, WASO, TIB, SE, including PSQI, HAM-A, Mental Alertness, and Sleep Quality, were also statistically assessed for the significant improvement within the group both for the treatment and the placebo groups in the healthy and the insomnia datasets. The obtained results suggest statistically significant (p < 0.0001) changes between the baseline values and the end of the study results except for the HAM-A and the mental alertness scores of the healthy subject group.

Conclusion: This study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well-tolerated by all the participants irrespective of their health condition and age.

A double-blind, randomized, placebo-controlled trial on the effect of Ashwagandha (Withania somnifera dunal.) root extract in improving cardiorespiratory endurance and recovery in healthy athletic adults. Tiwari, S.,Gupta, S. K., &amp; Pathak, A. K. (2021). Journal of ethnopharmacology, 272, 113929.

Results: At the end of the study, a statistically significant improvement in VO2 max outcome was observed in the Ashwagandha group when compared to the placebo group (P = 0.0074). The subjects in the Ashwagandha group also displayed a statistically significant increase at the end of the study when compared to the baseline (P &lt; 0.0001). Significantly improved TQR scores were observed in the Ashwagandha group members compared to their placebo counterparts (P &lt; 0.0001). DALDA questionnaire analysis in the Ashwagandha group was found statistically significant (P &lt;
0.0001) compared to the placebo group. RESTQ assessment also yielded better outcomes, especially for fatigue recovery (P &lt; 0.0001), lack of energy (P &lt; 0.0001), and fitness analysis (P &lt; 0.0001). The enhanced antioxidant level was significant (P &lt;0.0001) in the Ashwagandha group.

Conclusion: The present findings suggest that Ashwagandha root extract can successfully enhance cardiorespiratory endurance and improve the quality of life in healthy athletic adults.

Adaptogenic and Immunomodulatory Activity of Ashwagandha Root Extract: An Experimental Study in an Equine Model. Priyanka G, Anil Kumar B, Lakshman M, Manvitha V and Kala Kumar B. (2020). Front. Vet. Sci. 7:541112.

Results: Over the 21 days, a statistically significant (p < 0.05 increase was observed, in total erythrocyte count, total leucocyte count, hemoglobin content, lymphocyte percentage, reduced glutathione, and superoxide dismutase activities among the Ashwagandha treated groups (G2, G3, and G4) when compared to the control group (G1). The study also demonstrated a statistically significant decrease (p 0.05) in cortisol, epinephrine, glucose, triglycerides, creatinine, IL-6, alanine aminotransferase, and aspartate aminotransferase levels over the 21 days, in the Ashwagandha treated groups (G2, G3, and G4) when compared to the control group (G1). All the horses remained healthy throughout the study. There was no deviation from the normal values. At the end of the study, there was a non-significant increase, in the mean body weight of the horses in the treatment groups when compared to the control group.

Conclusion: The results suggest that Ashwagandha root extract has potent hemopoietic, anti- stress, antioxidant, adaptogenic, and immune-stimulant properties. The supplement was found safe for the horses. No adverse event was witnessed during the study period for any animal consuming the experimental herbal product.

Safety of Ashwagandha Root Extract: A Randomized, Placebo-Controlled, Study in Healthy Volunteers. Verma, N., Gupta, S. K., Tiwari, S., &amp; Mishra, A. K. (2020). Complementary therapies in medicine, 57, 102642.

Results: A detailed evaluation of the vital signs such as body weight, body temperature, pulse rate, respiratory rate, systolic and diastolic blood pressure, and Body Mass Index (BMI) were conducted for each participant at the baseline and the end of the study for treatment and placebo groups. Similarly, hematological and biochemical parameters were evaluated at the baseline and at the end the of study. The outcome did not indicate any untoward effects in any of the treated volunteers. No statistically significant change or abnormality was observed in the considered parameters including thyroid hormonal profile in both groups. No adverse events were reported by any of the participants in this study.

Conclusion: The present study revealed that the consumption of Ashwagandha root extract for 8 weeks was found to be safe, tolerable, and free from any unwanted toxic effects in healthy male and female participants. The physical, hematological, and
biochemical parameters measured for the participants were within normal limits. A further large-scale study is required to generalize the obtained outcomes.

Effect of an ashwagandha (Withania Somnifera) root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study. Gopal, S., Ajgaonkar, A., Kanchi, P., Kaundinya, A., Thakare, V., Chauhan, S. and Langade, D. (2021). J. Obstet. Gynaecol. Research, 47(12), 4414–4425.

Results: Among 100 participants enrolled, 91 participants completed the study. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in total MRS score (p &lt; 0.0001), reflected by significant reductions in the psychological (p = 0.0003), somato-vegetative (p = 0.0152), and urogenital (p < 0.0001) domains. Ashwagandha intake demonstrated a statistically significant reduction in total MENQoL scores (p < 0.0001) and was also associated with a statistically significant increase in serum estradiol (p < 0.0001) and a significant reduction in serum FSH (p < 0.0001) and serum LH (p < 0.05) compared with the placebo. There was no significant between the group differences in the serum testosterone level.

Conclusion: The results of this 8-week trial provide preliminary evidence that ashwagandha root extract is safe and effective in alleviating the climacteric symptoms in perimenopausal women. The mechanism by which ashwagandha helps to alleviate
perimenopausal symptoms could be a reduction in psychological symptoms and an increase in serum estradiol levels.

Effect of standardized root extract of ashwagandha (Withania somnifera) on well- being and sexual performance in adult males: A randomized controlled trial. Chauhan, S., Srivastava, M. K., &amp; Pathak, A. K. (2022). Health science reports, 5(4), e741.

Results: Compared to placebo, ashwagandha root extract supplementation was associated with a statistically significant increase in the total DISF‐M scores (mean difference −9.8; 95% confidence interval, −10.73 to −8.87; p < 0.0001; t‐test). It was also
associated with a statistically significant increase in serum testosterone levels (−66.52; −80.70 to −52.34; p < 0.0001; t‐test). However, the prolactin level did not change after intervention in both the ashwagandha and placebo groups (−1.06; −2.78 to 0.66; p > 0.05).

Conclusion: In conclusion, the findings of this study support ashwagandha root extract’s aphrodisiac effect on sexual well‐being in adult men. The mechanism by which ashwagandha helps to improve male sexual health could be due to an increase in serum testosterone. Thus, the ashwagandha root extract may be utilized to aid in the enhancement of male sexual function.

Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract for Improvement of Sexual Health in Healthy Women: A Prospective, Randomized, Placebo-Controlled Study Ajgaonkar A, Jain M, Debnath K (2022). Cureus, 14(10): e30787.

Results: There was statistically significant improvement (p < 0.0001) in FSFI scores with Ashwagandha [14.20 (0.98) at baseline to 22.62 (2.06) at week 8] as compared to placebo [14.17 (0.71) at baseline to 19.25 (2.23) at eight weeks], and this improvement was observed in all sub-scales (desire, arousal, lubrication, orgasm, sexual satisfaction, and pain) of the FSFI scale. There was a greater improvement (p < 0.0001) in FSDS scores with AG as compared to placebo. Although not statistically significant (p, 0.078), there was a greater reduction (improvement) in GHQ-28 scores at eight weeks with Ashwagandha as compared to placebo, and this trend was observed for all domains of GHQ-28 (global, physical, psychological, and social function). More women with Ashwagandha had improvement in SSEs at week 4 (p, 0.017) and week 8 (p, 0.002) as compared to placebo. Adverse events were comparable in the two groups. Two women reported nausea and one reported drowsiness with AG, whereas two reported nausea, one reported drowsiness and one reported nausea with drowsiness in the placebo group.

Conclusion: This study evaluated the efficacy and safety of Ashwagandha standardized root extract in improving sexual health in otherwise healthy women aged 18 to 50 years having HSDD. Significant improvements in the FSFI scores and FSDS scores were
observed with Ashwagandha. Oral administration of standardized Ashwagandha root extract for eight weeks improves female sexual health in otherwise healthy women who do not have any hormonal disturbances.

Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Salve, J., Pate, S., Debnath, K., &amp; Langade, D. (2019). Cureus, 11(12), e6466.

Results: The present randomized, double-blind, placebo-controlled clinical study evaluated the effect of an aqueous root extract of Ashwagandha in 58 participants having stress and anxiety. A significant reduction in PSS scores was observed with Ashwagandha 250 mg/day (P < 0.05) and 600 mg/day (P &lt; 0.001). Serum cortisol levels reduced with both Ashwagandha 250 mg/day (P < 0.05) and Ashwagandha 600 mg/day (P &lt; 0.0001). Compared to the placebo group participants, the participants receiving Ashwagandha had significant improvement in sleep quality.

Conclusion: Ashwagandha is a medically important herb and has a proven impact on human health. The findings from this study suggest that eight weeks of supplementation of aqueous Ashwagandha root extract was associated with a significant reduction of stress levels in individuals and improved overall quality of life. Hence, the use of this herb as a supplement for stress and anxiety management could be an excellent alternative option.

Efficacy and safety of standardized Ashwagandha (Withania somnifera) root extract on reducing stress and anxiety in domestic dogs: A randomized controlled trial Kaur J, Seshadri, S, Golla, K & Sampara, P (2022). Journal of Veterinary Behavior, 51, 8-15.

Results: In this 4-week, randomized, double-blind, placebo-controlled study, the administration of an Ashwagandha root extract (KSM-66 Ashwagandha®) at a dose of 15mg/kg body weight was associated with significant changes in the UCCr in dogs experiencing stress responses and anxiety when compared to the placebo. In comparison with the placebo, Ashwagandha intake was associated with a statistically significant reduction in urine cortisol to creatine ratio (P = 0.0005). Results from CBARQ revealed that Ashwagandha intake was associated with a statistically significant reduction in the fear and anxiety domain (P = 0.03), compared to placebo. There was also a statistically significant reduction in the CBPI pain severity (P < 0.0001) and pain interference (P < 0.0001) domains, compared to the placebo group.

Conclusion: Ashwagandha supplementation was well tolerated with no reported adverse events. The findings of this exploratory study suggest that Ashwagandha root extract may aid in attenuating signs of stress and anxiety in dogs.