Efficacy of Ashwagandha Extract Formulation (ASVAMAN®) on Improvement of Energy and Endurance: A Randomized, Double-blind, Placebo-controlled Clinical Study in Healthy Adults

Background: Ashwagandha (Withania somnifera) is a traditional herb that holds a significant place in Ayurvedic medicine, recognized as both a “rasayana” and “adaptogen”.

Objective: This study aimed to evaluate the effects of Ashwagandha root extract (ASVAMAN®) on the energy and endurance in healthy adults.

Methods: In this randomized, double-blind, placebo-controlled study, 40 healthy male participants with a body mass index (BMI) ranging from 20.0 to 25.9 kg/m2 were randomly allocated to receive either 300 mg of ASVAMAN® twice daily (n = 20) or a placebo (n = 20) for a duration of 42 days. The primary efficacy outcomes were evaluated using 6-minute walk test (6 MWT) scores and serum cortisol levels, measured from baseline to the conclusion of the study (42 days). Secondary outcomes were assessed using the stair climbing test (SCT), chair standing test (CST), 30-meter walk test (30 MWT), one-leg stance (OLS) test, serum testosterone levels, and 36-item short-form survey (SF-36) quality of life scores.

Results: Compared to the placebo group, Asvaman® supplementation led to a significant improvement (p < 0.001) in the 6 MWT distance score on day 42. Serum cortisol levels in the Asvaman® group significantly decreased from baseline to day 42, whereas levels in the placebo group remained unchanged. The Asvaman® group showed notable enhancements in SCT, CST, 30 MWT, OLS, and SF-36 scores, along with increased serum testosterone levels, compared to the placebo group.

Conclusion: These findings indicate that ASVAMAN® may serve as a viable alternative treatment for enhancing energy and endurance.

Introduction

Ashwagandha (Withania somnifera), an ancient medicinal herb used in Ayurvedic medicine, has garnered considerable attention in recent years owing to its potential to enhance energy levels and improve endurance. This adaptogenic herb, also referred to as Indian ginseng, has traditionally been employed to mitigate stress and promote overall well-being. It has gained significant attention in recent years for its potential to enhance energy levels and improve endurance in both athletic and nonathletic populations. This adaptogenic herb, widely used in traditional Ayurvedic medicine, has shown promising effects on cardiorespiratory endurance, physical performance, and overall quality of life [1], [2].

The active compounds in ashwagandha, primarily withanolides, are hypothesized to contribute to their energy-boosting and endurance-enhancing properties. These compounds have been demonstrated to modulate various physiological processes, including the regulation of cortisol levels, mitochondrial function, and oxidative stress [3]. Pharmacological investigations underscore its anti-inflammatory, immune-modulatory, antioxidant, anticancer, memory-enhancing, neuroprotective, hematopoietic, stress-reducing, and anxiolytic properties [4], [5].

Consequently, Ashwagandha root extract has emerged as a promising natural supplement for athletes, fitness enthusiasts, and individuals seeking to improve their physical stamina and mental resilience. Recent scientific investigations have explored the efficacy of Ashwagandha root extract in improving physical performance and reducing fatigue [6]. Studies have shown that Ashwagandha supplementation can lead to significant improvements in maximum aerobic capacity, a key indicator of cardiovascular fitness and endurance [2], [7]. Ashwagandha can increase muscle strength and reduce fatigue during physical activities [8] and has a positive impact on stress management, recovery, and fatigue reduction in athletes [2]. The antioxidant properties of herbs may contribute to these effects, potentially aiding post-exercise recovery and reducing oxidative stress [9]. At the cellular level, Ashwagandha enhances mitochondrial function in brown adipose tissue and skeletal muscle, potentially contributing to increased energy expenditure and improved endurance [10] This mechanism may explain, in part, the observed effects of the herb on physical performance and body composition. While much research has focused on physical performance, Ashwagandha’s benefits also extend to sexual health and fertility, with studies reporting improvements in sexual function and sperm quality [11], [12]. These findings further underscore the potential of the herb to enhance overall vitality and well-being. Recent clinical trials have explored its effects on various aspects of health, particularly focusing on how it might mitigate stress, boost stamina, and promote overall performance in both athletic and nonathletic populations. As research continues to uncover the multifaceted benefits of Ashwagandha root extract, its potential as a natural supplement to improve energy, endurance, and overall health has become increasingly apparent. However, more comprehensive clinical studies are required to fully elucidate the mechanisms of action and optimal dosing strategies for various populations and purposes. Notably, Asvaman^® stands as a standardized ashwagandha root extract. The purpose of this study was to evaluate the efficacy of the Asvaman^® formulation in improving energy and endurance in healthy adults.

Materials and Methods

Study Design

This randomized, double-blind, parallel, placebo-controlled, two-arm study was conducted at the Vatsalya Hospital Multispecialty Centre, Varanasi, Uttar Pradesh, with a sample size of 40. The subjects were randomized at a 1:1 (ASVAMAN^®: placebo) ratio, with 20 subjects per arm, and the study duration was 42 days. The study population was recruited from the outpatient department of the hospital. The study protocol (MN/EE/1121) was approved by the institutional ethics committee of the Vatsalya Hospital. The study was conducted in accordance with the principles of the Declaration of Helsinki (2013) and the International Conference on Harmonization (ICH) guidelines for Good Clinical Practice (ICH-GCP) E6 R2 (2016). The clinical trial was registered in the Clinical Trials Registry India (CTRI) (registration no. CTRI/2022/01/039548 (Registered on: 18th January 2022).

Study participants were allocated randomly to one of two groups: Asvaman^® or placebo, with a balanced ratio of 1:1. This allocation was accomplished using blocked randomization, where randomization codes were generated by an independent biostatistician utilizing computer-generated randomly permuted blocks. The codes were then enclosed within a sealed envelope and handed over to the investigator responsible for participant assignment. Throughout the duration of the study, only the biostatistician retained knowledge of these codes, ensuring their confidentiality. To maintain a double-blind environment, both the active study product and the placebo were manufactured and packaged in indistinguishable containers with matching labels. The complete analysis of the study outcomes was conducted under conditions of blinding, preserving the integrity of the study’s scientific rigor.

Study Population

Study Inclusion

The principal investigator explained the study procedures to the participants, clarified the queries, and obtained voluntary signed informed consent before screening. Participants were required to meet inclusion criteria, including being aged 18–50, willing to follow protocol requirements, mentally, physically, and legally eligible to give consent, having a male BMI between 20.0–25.9 kg/m², and willing to complete the study questionnaires.

Study Exclusion Criteria

Patients with pre-existing severe systemic disease, significant medical or psychiatric illness, history of cancer, neurological disorders, past treatment with health supplements, previous medication, influenza immunization, inability to comply, immune compromise, H1N1 vaccine vaccination, other reasons, or Covid-19 testing were excluded.

Extraction and Purification of Total Withanolides

A hydroalcoholic extract of ashwagandha root was prepared by Soxhlet extraction of powdered dried root material from Withania somnifera using 95% alcohol at 70°C for 3h in three successive batch extractions with a herb-to-solvent ratio of 1:4. After completion of extraction, the cooled liquid was refluxed at 65°C and concentrated by evaporating its liquid content in a rotary evaporator until dryness, with a total dissolved solid (TDS) of 95%–98%. The purification of total withanolide glycosides was done by using precipitation of water. After precipitation, the aqueous layer is separated by filtration. The precipitated mass is collected and vaccum tray dried and to get an approximate yield of 2%–3% w/w and standardized to contain 2.5% withanolide glycosides (WG).

Quantification of Total Withanolides

The total withanolides were quantified by reversed-phase high-performance liquid chromatography (RP-HPLC) using the USP method. Separation was achieved on a reversed-phase C18 column using a mobile phase gradient of potassium dihydrogen phosphate buffer and acetonitrile at a flow rate of 1.5 ml per min. Detection was performed using a UV detector at a wavelength of 227 nm.

Intervention (Treatment) and Dosing

Earlier clinical studies on healthy subjects using herbal products and different types of exercise have demonstrated significant improvements in energy and endurance. Based on the existing information, we hypothesized that ASVAMAN^® (manufactured by Manipal Natural Pvt. Ltd., Bangalore, Karnataka, India) supplemented capsules orally twice daily for 42 days (up to 6 weeks) in healthy subjects. Each capsule contained 300 mg of Ashwagandha extract with a standardized 2.5% of withanolide glycosides and excipients starch, which were administered twice a day after meals. The placebo capsule contains excipient starch without active ingredients and resembles ASVAMAN^® capsules in weight and all organoleptic characteristics. The two capsules were identical in appearance, shape, color, packaging, and texture.

Randomization and Blinding

The participants were randomized according to a pre-established schedule created using a computer-based randomization software. The randomization code given in the study product containers was used to randomly assign eligible patients to either trial arm. Randomization codes were generated by a computer using a permuted block design by an independent statistician. The sponsor’s design, investigator, subjects, and CRO’s design were all blinded to the study given to each participant, with the exception of the biostatistician. Throughout the duration of the study, only the biostatistician retained knowledge of these codes, ensuring their confidentiality. The ASVAMAN^® and placebo capsules were opaque, identical in color, size, and form, and were contained in similarly sized and labelled bottles. The investigator, research personnel, and participants were blinded to the identification of the investigational products (IP). To maintain a double-blind environment, both the active study product and the placebo were manufactured and packaged in indistinguishable containers with matching labels. Each subject was provided with one bottle of Investigational Product (IP) during day 42. Subjects were required to administer one capsule twice daily in the morning and evening after meals. In an eight-weeks, randomized, prospective, placebo-controlled, double-blind study, 40 men (aged 18 to 50 years) with little experience in resistance training were randomized into treatment (n = 20) and placebo (n = 20) groups. The subjects received 300 mg ASVAMAN^® twice daily or a starch placebo.

Outcome Measures

The primarily Outcome

The primary outcome of the study was to measure the biomarkers of serum cortisol and testosterone levels from baseline to the end of the study and to employ the six-minute walk test (SMWT) to determine whether treatment enhanced energy and fitness in healthy individuals. The primary outcome was assessed in both groups at baseline and at the end of the study (42 days). Serum cortisol is a widely employed biomarker for the assessment of physiological stress. The participant’s serum cortisol level was measured to evaluate alterations in cortisol levels within the body from the baseline of the study to its culmination. Serum cortisol levels were measured to assess the effects of Asvaman^® on physiological stress. The 6 MWT is a submaximal exercise test used to assess aerobic capacity and endurance in individuals under a variety of conditions. The 6 MWT can be used to track changes in exercise capacity over time, and it can also be used to compare the exercise capacity of different people. It is performed by having the participant walk as far as possible in 6 min, and the distance covered is measured in meters.

The Secondary Outcome

The secondary outcome of the study was the evaluation of score changes in the One Leg Stand, Stair Climb, Chair Stand, and 30 M Walk tests. Prior to administration of the medication and after completing the treatment, the Short Form 36 Health Survey Questionnaire (Quality of Life-SF 36) was used to indicate the health status of particular populations, help with service planning, and measure the impact of clinical and social interventions.

The Stair Climb Test (SCT) is a clinically relevant assessment of lower body strength, power, and physical function in older adults. It measures the time taken to ascend and descend stairs by using a handheld stopwatch. The chair stands test (CST) measures lower limb strength and endurance in older adults by measuring the time taken for a subject to complete 30 full stands with arms folded across their chest. The 30-meter Walk Test (30 MWT) measures lower extremity muscle performance and walking ability in people with various diseases. The One-Length Stance Test (OLS) is the most commonly used clinical tool for assessing postural steadiness in elderly individuals. The OLS test measures the number of seconds a participant stand with one leg balanced, with a maximum allowed time of 90 s. The 36-item Short Form Health Survey Questionnaire (SF36) is a widely recognized and extensively studied tool used to evaluate the quality of life (QoL) in relation to health. It encompasses eight distinct health domains and was used on both the baseline and day 42 of the study.

Testosterone also plays a crucial role in the development and proper functioning of the male body. Irregularities in testosterone levels have been associated with shifts in muscle mass and fat distribution, along with impacts on bone metabolism and energy levels in males [13]. In this study, serum testosterone levels were assessed at the beginning of the study and on day 42.

Statistical Analysis

Statistical analyses were performed using the statistical software SPSS with a significance level of P < 0.05, with a 95% confidence interval. It presented a descriptive study of baseline summary statistics, conducted inferential statistics using One-way ANOVA with Post hoc Tukey’s test for the main outcome and biomarker comparisons, and paired t-test for safety data. Intergroup comparisons were performed using unpaired t-tests.

Results

Standardization of herbal medicines is fraught with many challenges. In the present study, we have developed a simple, optimized, and validated HPLC method for the standardization of N. nucifera. Standardization of herbal medicines is fraught with many challenges. In the present study, we have developed a simple, optimized, and validated HPLC method for the standardization of N. nucifera. Standardization of herbal medicines is fraught with many challenges. In the present study, we have developed a simple, optimized, and validated HPLC method for the standardization of N. nucifera.

Demographic and Baseline Data

Forty-five male subjects were screened, of which 40 met the inclusion criteria and were enrolled in the study. The study included 20 patients in the ASVAMAN^® treatment group and 20 patients in the placebo group, with a 20.0 and 25.9 kg/m² BMI. Fig. 1 illustrates the distribution of participants in this study.

Fig. 1. CONSORT flow diagram: Participants checklist.

Following randomization, each group, the Asvaman^® and placebo groups, included 20 subjects. Two subjects from the Asvaman^® group and one from the placebo group dropped out, and 37 subjects completed the study. No differences were observed between the groups in terms of the baseline characteristics (Table I).

Table I. Demography and Baseline Characteristics of the Study Subjects at Baseline and Day 42

Parameters	Asvaman® group (n = 18)		Placebo group (n = 19)
	Baseline	Day 42	Baseline	Day 42
Pulse rate (bpm)	78.89 ± 6.76	80 ± 5.44	79.68 ± 4.63	79.16 ± 4.63
Respiratory rate (bpm)	16.55 ± 1.20	16.83 ± 1.10	16.0 ± 1.41	16.16 ± 1.07
Body temperature (°F)	98.37 ± 0.18	98.33 ± 0.17	98.37 ± 0.16	98.37 ± 0.18
Systolic blood pressure (mm/Hg)	118.89 ± 5.14	117.83 ± 6.98	118.68 ± 4.52	117.95 ± 4.85
Diastolic blood pressure (mm/Hg)	78.67 ± 6.54	77.22 ± 3.70	77.37 ± 4.32	76.42 ± 3.44
Note: *p < 0.05. Within the group comparison was made between baseline vs. day 42.

The standardization of herbal medicines is fraught with several challenges. With the growing demand for herbal drugs, the development of standardization tools will help maintain the quality control and herbal preparations of Ashwagandha. The quantification of withanolides in Withania somnifera was performed using the USP method by HPLC. Satisfactory separation was achieved using a mobile phase composed of potassium dihydrogen phosphate buffer and acetonitrile. As depicted in Fig. 2 the overlay HPLC chromatogram reveals the composition of Asvaman^®, which includes withanoside IV, withanoside V and VI, withaferin A, 12-Deoxywithastramonolide, withanolide A, withanone, and withanolide B. The retention times (RT) of the sample solution was overlaid with the standard solution, so the method was specific. The cumulative content of withanosides in Asvaman^® was determined to be 2.5%. These identified phytoconstituents within the formulation are known to be naturally occurring in W. somnifera, establishing the chemical profile of the extract.

Fig. 2. Overlaid HPLC Chromatogram of phytoconstituents present in Asvaman^® sample and Standard (Withanoside IV and Withanolide A).

The primary outcome for Asvaman^® and placebo groups, when assessed at the end of the study, was 42 days. The mean serum cortisol and six-minute walk test (SMWT) levels in both groups were similar at baseline; however, at the end of the study, there was a significant reduction in serum cortisol (p < 0.001) and a significant improvement in SMWT (p < 0.001) in ASVAMAN^® compared to placebo group (Fig. 3a and 3b). The outcome was statistically significant when compared to the baseline and end of the study in the active group (p ≤ 0.05). Between-group comparison analysis on day 42, showed a significant (p < 0.001) improvement in 6 MWD in the Asvaman^® group at all evaluation points, and the serum cortisol level in the Asvaman^® group was lower than that in the placebo group. This indicates that ASVAMAN^®️ is a good way to boost energy and endurance.

Fig. 3. Changes in (a) serum cortisol levels and (b) 6MWD of the study subjects at baseline and day 42.

The data (Table II) pertaining to secondary outcomes were assessed for both groups at baseline and at the end of the study (42 days) and are summarized. The Asvaman^® and placebo groups demonstrated significantly increased differences (p < 0.001) in the OLS test results from baseline to day 42 within the group analysis, whereas there was no significant difference in the OLS score between the groups at day 42. The results also showed a significant reduction in SCT time (p < 0.001), CST time (p < 0.001), and 30 MWT time (p < 0.001) in the Asvaman^® group on day 42 compared to baseline within the group. However, there was no significant group difference in SCT and OLS times on day 42 between the groups. There was a significant improvement in CST time (p < 0.001) and 30 MWT time (p < 0.001) between groups on day 42. This finding was statistically significant (p ≤ 0.05). A significant increase in serum testosterone levels (p< 0.001) also was observed in the Asvaman^® group compared to the placebo group at day 42 within the group. On day 42, a comparison between the groups showed that the Asvaman^® group had significantly higher serum testosterone levels than the placebo group.

Table II. Assessment of SCT, CST, 30MWT, OLS Scores and Serum Testosterone Levels of the Study Subjects at Baseline and Day 42

Variables	Asvaman® group (n = 18)		Placebo group (n = 19)
	Baseline	Day 42	Baseline	Day 42
SCT (Sec)	15.20 ± 1.35	9.66 ± 1.05***	14.89 ± 1.64	9.26 ± 0.81***
CST (Sec)	49.55 ± 3.78	23.72 ± 3.04***	50.37 ± 4.46	30.31 ± 3.54***
30MWT (Sec)	2.49 ± 0.30	1.06 ± 0.05***	2.37 ± 0.43	1.23 ± 0.14***
OLS (Sec)	46.0 ± 8.25	127.22 ± 6.81***	52.89 ± 11.10	121.0 ± 23.34***
S. Testosterone (ng/dl)	428.16 ± 180.16	552.57 ± 174.73***	448.15 ± 172.66	469.46 ± 185.07
Note: ***p < 0.001. Within the group comparison was made between baseline vs. day 42.

Table III depicts the SF36 survey scores at baseline and day 42. The mean SF36 survey scores of QoL were analysed for the Asvaman^® and placebo groups. Both Asvaman^® and placebo groups had higher scores for physical functioning, emotional role, social function, and bodily pain. However, role limitation due to physical health, energy/fatigue, and general health remained unchanged. The Asvaman^® group showed some improvement in physical functioning, emotional role, social function, and bodily pain scores, but no significant improvement in role limitation physical health, energy/fatigue, and general health scores compared to the placebo group. Thus, concluding that ASVAMAN^® improved the quality of life of patients. All the secondary outcomes showed statistically significant indicating the effectiveness of ASVAMAN^® in improving energy and endurance.

Table III. Assessment of SF36 Survey Scores measuring the QoL of the Study Subjects at Baseline and Day 42

Variables	Asvaman® group (n = 18)		Placebo group (n = 19)
	Baseline	Day 42	Baseline	Day 42
Physical functioning (scores)	22.22 ± 20.81	41.67 ± 22.69	30.26 ± 22.94	46.05 ± 25.36
Role limitation due to physical health (scores)	69.44 ± 13.71	69.72 ± 14.29	67.10 ± 8.99	68.16 ± 18.95
Role limitations due to emotional problems (scores)	24.07 ± 25.06	55.56 ± 36.16	22.81± 24.97	43.86 ± 43.11
Energy/fatigue (scores)	46.91 ± 5.95	44.57 ± 8.54	46.31 ± 7.56	44.21 ± 12.01
Social functioning (scores)	30.55 ± 14.99	55.56 ± 36.16	32.89± 11.94	44.08 ± 20.57
Pain (scores)	21.25 ± 11.42	42.36 ± 21.06	21.31 ± 12.48	30.66 ± 17.50
General health (scores)	50.92 ± 6.48	45.83 ± 11.25	51.75 ± 4.87	49.12 ± 16.17
Note: ***p < 0.001. Within the group comparison was made between baseline vs. day 42.

Discussion

In this randomized placebo-controlled clinical study, we evaluated the effects of ashwagandha extract (Asvaman^® 300 mg) capsules on improvement of energy and endurance in healthy human volunteers. As evidenced by a growing body of scientific exploration, Ashwagandha stands not only as a historical gem within Ayurvedic tradition but also as a modern focal point of research and discovery, offering a wealth of potential for holistic well-being and enhanced quality of life.

Cortisol play crucial roles in energy metabolism and endurance performance, as evidenced by several clinical trials. Our assessment encompassed the enhancement of physiological stress levels and sexual well-being through the measurement of serum cortisol and testosterone concentrations subsequent to the administration of Asvaman^®. The presence of cortisol within the bloodstream is intricately interwoven with stress levels. Instances of stress, whether originating from physical or psychological sources, trigger an augmented secretion of adrenocorticotropic hormone (ACTH), thereby resulting in an elevation of cortisol levels [14] The outcomes of our study manifest a significant finding, revealing a substantial reduction (p < 0.001) in serum cortisol levels following a 42-day regimen of Asvaman^® treatment. Ashwagandha extract has shown promising effects on cortisol and testosterone levels, as well as improvements in energy and endurance in adults. Studies have demonstrated that ashwagandha supplementation is associated with significant reductions in cortisol levels compared to placebo [15], [16]. This modulation of the hypothalamus-pituitary-adrenal axis may contribute to ashwagandha’s stress-relieving properties [17]. In alignment with this outcome, prior research endeavours involving human participants have consistently yielded comparable outcomes through the utilization of ashwagandha extract [5], [15]. These investigations, paralleling the current findings, further substantiate the efficacy and reliability of ashwagandha’s effects. Such a consistent pattern of results across various studies highlights the robustness of the observed outcomes and enhances our confidence in the potential benefits of ashwagandha extract.

Several studies have shown that ashwagandha extract improves various aspects of physical performance and endurance, including exercise capacity, muscle performance, postural steadiness, lower limb strength, and endurance [18], [19]. The findings of this study indicated that Asvaman^® supplementation for 42 days showed significantly greater improvements in 6MWD, SCT, CST, and 30MWT scores compared to placebo (Fig. 3b and Table II). These improvements after Asvaman^® supplementation were consistent with earlier studies. The observed improvements in exercise capacity, muscle performance, postural stability, lower limb strength, and endurance post Asvaman^® supplementation resonated harmoniously with prior research, thereby further substantiating its efficacy. The consistent findings of improved muscular strength and power indicate that ashwagandha supplementation may positively impact various aspects of physical performance and energy levels [1], [2], [19]. Antecedent investigations have illuminated the potential of ashwagandha supplementation in fostering amplified serum testosterone levels among human volunteers [11], [20]. In line with these antecedents, the current study affirms that the utilization of Asvaman^® capsules for a span of 42 days effectively engendered a rise in serum testosterone levels in comparison to the placebo group (Table II). The implications of this outcomes reverberate with prior research that has harnessed ashwagandha extract to augment and sustain the dimensions of normal sexual well-being in adult males of sound health. Consequently, our study integrates seamlessly with the existing body of knowledge, reinforcing the notion of ashwagandha’s potential utility in ameliorating sexual health and managing stress-related cortisol fluctuations.

The assessment of the impact of interventions on physical and mental well-being often relies on the SF36 QoL questionnaire. Within the scope of this study, the effectiveness of the interventions was evaluated through a self-reported SF36 questionnaire encompassing eight distinct subdomains. These subdomains comprised physical functioning, role physical, role emotional, energy/fatigue, social functioning, bodily pain, general health, and emotional well-being. The results of the study indicated that the introduction of Asvaman^® supplementation exhibited notable enhancements across various components of the SF36 scores in comparison to the placebo, particularly demonstrating significant improvements in physical functioning (p < 0.05), role emotional (p < 0.01), social functioning, and bodily pain-highlighting their substantial contributions to overall QoL (Table III). Notably, the domains encompassing role limitation due to physical health, energy/fatigue, general health, and emotional well-being displayed limited improvements within the Asvaman^® group, closely resembling the changes witnessed in the placebo group. This pattern of response suggests the possibility that achieving notable enhancements in these specific domain scores might have required a higher dosage of Asvaman^® or a more extended period of administration. Nonetheless, it is noteworthy that discernible improvements were evident in certain components of the SF36 parameters, underscoring the potential of Asvaman^® to elevate overall QoL and well-being, particularly among the cohort of healthy volunteers. This observation opens avenues for further investigation into optimizing the dosing regimen and exploring the broader impact of Asvaman^® on diverse aspects of QoL.

Conclusions

Overall, the results of this study have demonstrated statistically and clinically significant efficacy for the treatment group subjects supplemented with ASVAMAN^® when compared to placebo. The efficacy results demonstrated a strong positive trend in the primary efficacy parameter such as serum cortisol levels and six-minute walk test (SMWT) score, suggesting a positive response in treatment arm ASVAMAN^® multi-parameter assessments revealed the treatments ASVAMAN^® to be more efficacious than placebo. Taken together, the primary and secondary efficacy parameters from this study makes a strong argument that ASVAMAN^® could provide comparable improvement in energy level and endurance over placebo (P).

References

• Choudhary B, Shetty A, Langade D. Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults. Ayu. 2015;36(1).
• Tiwari S, Gupta S, Pathak A. 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. J Ethnopharmacol. 2021;272.
• Singh N, Yadav S, Rao A, Nandal A, Kumar S, Ganaie S. Review on anticancerous therapeutic potential of Withania somnifera (L.) Dunal. J Ethnopharmacol. 2021;270.
• Kalra R, Kaushik N. Withania somnifera (Linn.) Dunal: a review of chemical and pharmacological diversity. Phytochem Rev. 2017;16.
• Salve J, Pate S, Debnath K, Langade D. Adaptogenic and anxiolytic effects of Ashwagandha root extract in healthy adults: a double-blind, randomized, placebo-controlled clinical study. Cureus. 2019;11(12).
• Chandrasekhar K, Kapoor J, Anishetty S. 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. Indian J Psychol Med. 2012;34.
• Sandhu J, Shah B, Shenoy S, Chauhan S, Lavekar G, Padhi M. Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults. Int J Ayurveda Res. 2010;1(3).
• Choudhary D, Bhattacharyya S, Joshi K. Body weight management in adults under chronic stress through treatment with Ashwagandha root extract. J Evid Based Complement Altern Med. 2017;22(1):96-106.
• Trivedi M, Panda P, Sethi K, Jana S. Metabolite profiling in Withania somnifera roots hydroalcoholic extract using LC/MS, GC/MS and NMR spectroscopy. Chem Biodivers. 2017;14(3).
• Lee D, Ahn J, Jang Y, Seo H, Ha T, Kim M. Withania somnifera extract enhances energy expenditure via improving mitochondrial function in adipose tissue and skeletal muscle. Nutrients. 2020;12(2).
• Ambiye V, 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;2013:1-6.
• Chauhan S, Srivastava M, Pathak A. Effect of standardized root extract of Ashwagandha (Withania somnifera) on well-being and sexual performance in adult males: a randomized controlled trial. Health Sci Rep. 2022;5(4).
• Kelly D, Jones T. Testosterone: a metabolic hormone in health and disease. J Endocrinol. 2013;217(3):R25-45.
• Kageyama K, Iwasaki Y, Daimon M. Hypothalamic regulation of corticotropin-releasing factor under stress and stress resilience. Int J Mol Sci. 2021;22(22).
• Lopresti A, Smith S, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: a randomized, double-blind, placebo-controlled study. Medicine. 2019;98(37).
• Remenapp A, Coyle K, Orange T, Lynch T, Hooper D, Hooper S. Efficacy of Withania somnifera supplementation on adult’s cognition and mood. J Ayurveda Integr Med. 2021;13(2).
• Smith S, Lopresti A, Fairchild T. Exploring the efficacy and safety of a novel standardized Ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2023;37(11).
• Tripathi R, Salve B, Petare A, Raut A, Rege N. Effect of Withania somnifera on physical and cardiovascular performance induced by physical stress in healthy human volunteers. Int J Basic Clin Pharmacol. 2016;5(6).
• Ziegenfuss T, Kedia A, Sandrock J, Raub B, Kerksick C, Lopez H. Effects of an aqueous extract of Withania somnifera on strength training adaptations and recovery: the STAR Trial. Nutrients. 2018;10(11).
• Wankhede S, Langade D, Joshi K, Sinha S, Bhattacharyya S. Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. J Int Soc Sports Nutr. 2015;12(1).