Ashwagandha: A Case Example of the Supplement Industry
Perhaps ashwagandha may aid in stress management, athletic performance, and sleep, but this effect is far from definitive.
The dietary supplement industry is akin to the lawless early days of Western America—rumors of untouched gold abound, ripe for the taking. It contrasts the well-kempt pharmaceutical drug industry, where regulatory processes and overabundant scrutiny reign. Nevertheless, patients, time after time, demonstrate a preference for easily understood claims of herbal supplements and non-FDA-monitored products.
Ashwagandha is the perfect modern example of an herbal product, an all-in-one remedy claimed to aid in anxiety, sleep, low testosterone, athletic performance, and more, according to supplement companies and online influencers. In the United States, this herbal supplement's sales grew dramatically from 2020 to 2021 to total over 94 million dollars in revenue.1 A brief search on Amazon's best-seller list reveals ashwagandha's foothold at 61st for "health and household" and 10th for "vitamins, minerals, and supplements." But is this supplement really efficacious, safe, and living up to its claims?
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Prominent, top-selling ashwagandha brands such as Nature Made, Goli, and Nature's Bounty promise overall mood improvement. A 2022 systematic review of ashwagandha's effect on anxiety and stress modulation included 12 randomized, double-blind, placebo-controlled trials totaling 1,002 participants. Doses ranged from 240 to 1000 mg daily, with one outlier trial of 12,000 mg, but specific extracts were not mentioned. Eight of these trials utilized the Hamilton anxiety rating scale or depression anxiety stress scale–21 to measure anxiety, and pooled estimates showed significant anxiety improvement with a standard mean deviation of -1.55 (p-value 0.005). In 7 trials, stress was measured using either the modified Hamilton Anxiety Rating Scale (HAM-A), Perceived Stress Scale (PSS), Depression Anxiety Stress Scale (DASS), or Recovery-Stress Questionnaire for Athletes (RESTQ-Sport). Again, pooled improvement was significant, with a standard mean deviation of -1.75 (p <0.005) for stress survey scores.2
Other health claims of ashwagandha include improved athletic performance, sleep, and hormone balance. Popular platforms such as YouTube, Instagram, and TikTok host numerous videos promising a return to the sleep and strength of a teenager. A systemic review and meta-analysis was conducted on sleep quality. It included 400 patients across 5 randomized placebo-controlled trials, all within India. The total duration of these studies ranged from 6 to 12 weeks. Four studies utilized KSM-66, a standardized ashwagandha extract manufactured by Ixoreal, and one study utilized Shoden extract, another standardized extract manufactured by NutriScience Innovations, with doses varying from 120 mg daily to 600 mg daily. Results showed significant improvements in subjective sleep measures using the Sleep Quality Scale and Pittsburg Sleep Quality Index. Objective measurements also significantly improved, including sleep onset latency, total sleep time, wake time after sleep onset, and sleep efficiency (p<0.05).3
Another systematic review published in 2021 included 12 randomized placebo-controlled studies with 615 total patients, this time focusing on athletic performance. Lower limb/upper limb one repetition maximum (squat/bench press), relative speed/power (barbell velocity), and testosterone concentrations significantly increased with ashwagandha (p <0.05), and VO2 max and blood hemoglobin significantly increased as measures of cardiovascular fitness.
Their final category of athletic performance—recovery—revealed similar results. Muscle fatigue improvement, sleep recovery, and cortisol concentration reductions were significant with ashwagandha compared to placebo (p <0.05). The authors conclude there may be some benefit to physical performance with ashwagandha over placebo. Ashwagandha doses ranged from 120 to 1250 mg daily and were from 3 different ashwagandha extracts: Sensoril, KSM-66, and Shoden.4 The greatest caveat pertains to the study population. All studies except for one used untrained individuals to test these athletic outcomes. The question remains whether ashwagandha benefit an already-trained athlete.
Perhaps extreme internet claims stem from a grain of truth, but what about safety outcomes? All previously mentioned trials report no significant adverse events.2-4 A 2020 article discussed the pharmacological properties of this supplement and cited animal data for a potentially toxic dose threshold. Intraperitoneal injections of ashwagandha root extract were lethal at 1260 mg/kg of body weight, far above the doses utilized in almost all human studies.5 A 2020 randomized, double-blind placebo-controlled trial enrolled 80 healthy adults and measured biomarkers such as thyroid stimulating hormone, thyroxine, aspartate transaminase and alanine transaminase, blood pressure, and hemoglobin. There were no differences after 8 weeks of 300 mg daily of ashwagandha, although this dose is much lower than in some trials. Interestingly, blood hemoglobin in this study did not change in contrast to the earlier meta-analysis. Another important note is the average age of participants, which was 30 years old.5 Deviating from healthy patients, one 2017 randomized, double-blind, placebo-controlled trial in India enrolled subclinical hypothyroid patients with baseline TSH levels of 4.5-10 μI U/L. After 8 weeks, TSH levels improved significantly in the treatment group versus placebo (p <0.001).6 However, there are case studies that demonstrate adverse effects, primarily hepatotoxicity.7
The abundance of literature on ashwagandha highlights the scientific interest in this ancient Ayurveda traditional herb. However, the inescapable nature of the supplement market should remind consumers and health care practitioners of a daunting problem. Which extract and which dose should patients take? The lack of imposed monitoring allows for a wide range of confusing products. It is entirely on the patient to sift through countless potentially ineffective and misleading supplements. A 2023 case series study found that 89% of botanical athletic performance supplements did not contain what their label claimed out of 63 products tested.8 Though this study did not include ashwagandha, it is reasonable to remain skeptical of most unmonitored dietary supplements.
The ultimate message to patients should be one of caution. Perhaps ashwagandha may aid in stress management, athletic performance, and sleep, but this effect is far from definitive.
In addition, this supplement lacks adequate testing in patients with comorbidities such as diabetes, hypertension, immunocompromising conditions, and clinical thyroid disorders. Case studies show potential hepatotoxicity with this supplement, and almost all studies have short durations of up to 3 months. If a patient chooses to use this supplement, they should opt for a well-studied standardized extract such as KSM-66, Sensoril, or Shogan, and doses above 1250 mg daily are generally not recommended due to a lack of data. Health care providers must continue to remain the first line of medical knowledge for the safety of patients, and this includes understanding newly popular dietary supplements like ashwagandha.
About the Author
Garrett Meggs, PharmD, is a PGY-1 Ambulatory Care Resident at AdventHealth Celebration.
References
1. Grebow J. Ashwagandha’s sales growth slows down: 2023 ingredient trends for food, drinks, dietary supplements, and natural products. Nutritional Outlook. February 8, 2023. Accessed September 10, 2023.
2. Akhgarjand C, Asoudeh F, Bagheri A, et al. Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2022;36(11):4115-4124. doi:10.1002/ptr.7598
3. Cheah KL, Norhayati MN, Husniati Yaacob L, Abdul Rahman R. Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis. PLoS One. 2021;16(9):e0257843. Published 2021 Sep 24. doi:10.1371/journal.pone.0257843
4. Bonilla DA, Moreno Y, Gho C, Petro JL, Odriozola-Martínez A, Kreider RB. Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis. J Funct Morphol Kinesiol. 2021;6(1):20. Published 2021 Feb 11. doi:10.3390/jfmk6010020
5. Verma N, Gupta SK, Tiwari S, Mishra AK. Safety of Ashwagandha Root Extract: A Randomized, Placebo-Controlled, study in Healthy Volunteers. Complement Ther Med. 2021;57:102642. doi:10.1016/j.ctim.2020.102642
6. Sharma AK, Basu I, Singh S. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018;24(3):243-248. doi:10.1089/acm.2017.0183
7. Lubarska M, Hałasiński P, Hryhorowicz S, et al. Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. Int J Environ Res Public Health. 2023;20(5):3921. Published 2023 Feb 22. doi:10.3390/ijerph20053921
8. Cohen PA, Avula B, Katragunta K, Travis JC, Khan I. Presence and Quantity of Botanical Ingredients With Purported Performance-Enhancing Properties in Sports Supplements. JAMA Netw Open. 2023;6(7):e2323879. Published 2023 Jul 3. doi:10.1001/jamanetworkopen.2023.23879
