Reference
Verma N, Gupta SK, Patil S, Tiwari S, Mishra AK. Effects of ashwagandha (Withania somnifera) standardized root extract on physical endurance and VO2max in healthy adults performing resistance training: an eight-week, prospective, randomized, double-blind, placebo-controlled study. F1000Res. 2024;12:335.
Study Objective
To examine the effects of a standardized Withania somnifera (Ws) extract on changes in muscle strength, muscle growth, and cardiorespiratory endurance in active, healthy participants of both sexes
Key Takeaway
Withania somnifera, 600 mg quaque die (QD), vs placebo, 600 mg QD, was a safe supplement in males and females, aged 18 to 45 years, engaged in resistance training, and led to some significant improvements, but not uniformly among the sexes.
Design
Parallel groups, 8 weeks, multicenter, randomized, double-blind, placebo-controlled
Participants
Healthy adults of either sex, aged 18 to 45 years, engaging in regular physical activity, including working out at a gymnasium and doing strength-training exercises, for at least the previous 3 months. Investigators recruited 80 participants, 40 in the treatment group and 40 in the placebo group.
Exclusion criteria included taking nutritional supplements, medications, or steroids to enhance physical performance, a history of drug abuse, smoking more than 10 cigarettes per day, consuming more than 14 grams of alcohol per day, plans to participate in a sporting event during the trial, weight loss of more than 5 kg in the past 3 months, history of orthopedic injury or surgery in the past 6 months, known hypersensitivity to Ws, participation in a clinical trial in the past 3 months, history of heart disease, diabetes, depression, stroke, or neurological disorder, and taking antihypertensive drugs, betablockers, beta-agonists, hormonal contraceptives, corticosteroids, or psychotropic substances in the prior 3 months.
Intervention
Twice daily, participants took 1 capsule, with milk or water, of either Ws (300 mg/capsule, standardized to 5% withanolides [KSM-66, Ixoreal Biomed, California]) or a placebo (300 mg/capsule starch [Shri Kartikeya Pharma, Hyderabad, India]). Withanolide standardization occurred via high-performance liquid chromatography (HPLC) and was confirmed by Shri Kartikeya Pharma, Hyderabad, India.
Study Parameters Assessed
Resistance training focused on improving muscle strength and muscle size and enhancing cardiorespiratory resistance. Investigators followed the National Strength and Conditioning Association’s regulations and guidelines, with training on alternate days (3 days/week) and 1 day of complete rest per week. The training consisted of low-intensity aerobic exercise as a warm-up and then performance of maximum repetitions for each set until exhaustion. Figure 1 of the study shows details.
Investigators assessed muscle strength by 1 repetition maximum for bench press and leg press on day 1 and at the end of 8 weeks. At those same time points, they assessed muscle size at 3 sites—flexed mid-upper arm, chest at mid-tidal volume, and upper thigh inferior to the gluteal fold—using the Moritani–deVries method.
Maximal oxygen consumption used the Bruce protocol on a treadmill. This was done on day 1 and at the end of 8 weeks. Other tests were biochemistry, hematology, renal, liver, thyroid, and vital signs.
Statistical Analysis
Investigators used MedCalc (version 20.011) for statistical analyses. They performed efficacy analysis on the modified intention to treat and safety analysis on the whole data set. Statistical significance was set at P<0.05.
Key Findings
Investigators screened 92 people; 80 met the inclusion criteria and were enrolled. All completed the 8-week trial, but 4 in the placebo group (3 males, 1 female) and 3 in the treatment group (3 males) did not consume their treatment after the second week and were excluded from the efficacy analysis.
There were no significant differences between the 2 groups based on baseline measurements.
Muscle strength from within-group analysis demonstrated a significant increase in bench press and leg press in both males and females over the 8-week trial. Muscle size also increased over the 8 weeks, with a significant increase in female chest size (P=0.006); male mid-arm circumference (P=0.009); and female thigh circumference (P=0.009). Changes in endurance (as measured by VO2max) had a greater improvement in males (P<0.0001), females (P<0.0001), and the total Ws group compared to placebo by about 8%.
Neither group experienced any serious side effects. Investigators did not observe any significant changes in hematology, renal, liver, and thyroid function tests or vital signs from baseline to end of 8 weeks.
Transparency
Author roles were delineated at the end of the paper, no competing interests were declared, and no grants supported this trial. The study was approved by the Institutional Ethics Committee of both King George’s Medical University and the M V Hospital and Research Centre, registered with the Clinical Trials Registry of India, and conducted in compliance with the Declaration of Helsinki Guidelines, the New Drugs and Clinical Trial Rules of 2019, and the Indian Council of Medical Research.
Practice Implications
Withania somnifera significantly improved muscle strength, muscle size (with results varying by muscle group and sex of participants), and maximum VO2 in both sexes. These findings are similar to the review of 12 trials in a meta-analysis by Bonilla et al in 2021.1 Only 2 of the 12 trials assessed muscle strength. It should be noted that there was no significant change in body fat percentage, but the Ws group had significantly lower body mass index (BMI; P=0.004) and weight (P=0.005), and while statistically significant, this outcome may not be clinically significant.
Animal data and limited human data from a recent literature review suggest it is a probable endocrine, with a role in the hypothalamic-pituitary-adrenal (HPA)–axis related to its clinical effects.
Some of my concerns, shared by the reviewers, include the participants taking Ws or placebo with milk (a protein source) vs water; the loss of subjects to noncompliance with treatment; absence of androgen labs to measure testosterone, dehydroepiandrosterone (DHEAS), estradiol, and progesterone; and absence of data on food intake and its macronutrient content, protein, fats, and carbohydrates. Testing androgens could detect if any subjects were using exogenous sources to enhance their strength and performance. The participants were already engaged in resistance training, so these results may not be applicable to untrained or casually trained adults or those outside the ages of 18 to 45 years. Diet during strength training can significantly affect outcomes, so the absence of a controlled diet, or at least the tracking of diet and noting if changes occurred, could have an impact on outcomes.
Bonilla et al’s attribution of Ws being an antioxidant was speculation and not supported by any measurements from the reviewed trials. Animal data and limited human data from a recent literature review suggest it is a probable endocrine, with a role in the hypothalamic-pituitary-adrenal (HPA)–axis related to its clinical effects.2 Development of acne is a side effect I have seen in a few female patients, but it did not appear as a side effect in this trial.
