Ashwagandha: Overview, Efficacy, Risk

With the use of supplements being a popular practice, it likely comes as no surprise that a plant-based anti-stress and anti-anxiety supplement has been advertised extensively. Withania somnifera, more frequently referred to as ashwagandha, has been touted for its beneficial capabilities, with significant implications regarding its ability to reduce stress levels.¹ Despite its many claims, however, sufficient information is questionable as to the benefits it provides. A further look at the history of its use as well as its evidential efficacy is warranted, particularly due to the widespread recommendations of its use.

History

Ashwagandha is a plant from which the root and berries have historically been used to create medicinal compounds. Utilized by Ayurvedic, Indian and Unani medicine, ashwagandha has been prescribed for a whole host of physical and mental maladies ranging from arthritis, tumors and tuberculosis to stress, difficulty thinking and anxiety.¹ In a brief review article referencing ashwagandha, one author stated that the health implications for this plant are extensive, being consistently used in Indian and Ayurvedic medicine.² Further the author stated that particularly noteworthy amongst uses were implications of benefit for tumors, inflammation, infectious diseases, fevers and inflammatory conditions.^{2, 3} However, despite the plethora of assumed uses, the author noted that the traditional use of this plant “may not be supported by scientific studies”.² In addition to the long list of illnesses ashwagandha is suggested to treat, it is also commonly referred to as an adaptogen (possessing the ability to aid the body in the normalization and regulation of systemic stress).¹ Ashwagandha has frequently been used as a naturally-occurring anti-stress and anti-anxiety agent, which will be the central focus of this paper.¹

Efficacy

In a review of clinical studies, authors examined the research surrounding the evidential usefulness of plant-based medicines as anxiolytics.⁴ Of the 21 plants with research pertaining to human clinical trial evidence, 13 showed anxiolytic effects when used in durations longer than one day, one of which was ashwagandha.⁴ Though positive effect was observed, authors further stated that the difference between the outcome of ashwagandha administration compared to placebo was not statistically significant.⁴ Authors stated that conclusions should be taken cautiously as many of the studies contained study limitations such as small sample sizes, brief intervention periods, and non-replication.⁴

In a double-blind, randomized, placebo-controlled study, researchers looked at the effect of ashwagandha extract capsules (formulated from the roots and leaves) on chronically stressed humans.⁵ The 98 subjects who completed the study were divided into four groups, three with various dosages and frequency of dosages and one control group.⁵ Results showed improvement of anxiety ratings in all of the treatment groups when compared to placebo, thus leading researchers to conclude that the claims regarding ashwagandha’s anxiolytic effects were warranted.⁵ However, it is important to note that not only was the research performed with the financial support of Natreon Inc., the patent holder of withania somnifera but several of the researchers were employed or worked voluntarily at Natreon  or NutraGenesis LLC, a retailer of withania somnifera.⁵ Therefore, the results of this study should be accepted cautiously, due to the financial investment and potential benefit these results may provide the companies involved.⁵

Looking at the anxiolytic efficacy of an ethanolic extract of withania somifera (tablet form), a double-blind, placebo-controlled evaluation was performed with 39 subjects diagnosed with ICD-10 generalized anxiety disorder, mixed anxiety and depression, panic disorder, and adjustment disorder with anxiety.⁶ Participants were evaluated at two and six weeks using the Hamilton Anxiety Scale, the Global Rating Scale and the Systematic Assessment for Treatment Emergent Effects (SAFTEE) symptom checklist.⁶ Commenting on participant dropout during the study, researchers stated that upon investigation, drop-outs occurred due to lack of benefit, adverse side effects, need for increased medication and undisclosed reasons.⁶ Following a review of results, researchers concluded that a demonstration of ashwagandha’s anxiolytic effects was evident and proved superior than placebo at the two-week follow-up and statistically significant at the 6-week follow-up.⁶ Once again of note, the research study was supported by a grant provided by Gufic LTD, Bombay, the manufacturer of the ashwagandha formulation tested.⁶ Though this acknowledgement does not infer automatic inferiority of the study results, it does give rise for additional caution of study bias.

In a randomized controlled trial, researchers examined the efficacy of naturopathic care for patients with anxiety.⁷ All participants suffered from moderate to severe anxiety for at least six weeks prior to the beginning of the study.⁷ Forty-one subjects received naturopathic care (NC) and forty subjects received standardized psychotherapy (PT), both for a duration of 12 weeks.⁷ Subjects in the NC group received several forms of treatment including dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin and ashwagandha (extracted from the root).⁷ Similarly, the PT group engaged in several treatments including deep breathing relaxation techniques and placebo.⁷  Intended to measure anxiety, mental health, and overall quality of life, results were evaluated using the Beck Anxiety Inventory (BAI), the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP).⁷ Participants were observed for at least eight weeks, during which time, BAI scores decreased by 56.5% in the NC subjects compared to 30.5% in the PT subjects.⁷ Further, significant differences presented with the two groups, with the NC group demonstrating greater clinical benefit in the areas of mental health, concentration, fatigue, social functioning, vitality, and overall quality of life.⁷ Though both groups demonstrated improvement in levels of anxiety, researchers concluded that the NC group benefited more from treatment when compared to the PT group.⁷ One limitation worth noting is the variety of NC treatments employed makes it difficult to draw conclusions regarding the efficacy of any one factor.⁷ Therefore, in regard to the positive effect of ashwagandha based on this research, it may only prove to be a potential element for benefit with the necessity of further research. Though results showed positive effect for naturopathic treatment, including the use of ashwagandha, the products used in the study were supplied free of charge by the company who makes them, thus possibly giving rise to caution yet again.⁷

One prospective, randomized, double-blind, placebo-controlled study was performed to determine the efficacy of a high-concentration, full-spectrum extract of ashwagandha root when administered to adults suffering from stress and anxiety.⁸ Based upon the premise that Ayurvedic medicine, animal studies and clinical studies all point to ashwagandha’s safe and effective role as an adaptogen, researchers looked at 64 participants with a history of experiencing chronic stress.⁸ Through the use of measured serum cortisol levels as well as stress-assessment questionnaires, researchers evaluated the effect of ashwagandha on the participants.⁸ Results indicated significant reduction in symptoms on all measures in the ashwagandha group when compared to the placebo group.⁸ Further, serum cortisol levels decreased substantially in the ashwagandha group when compared to the placebo group.⁸ Researchers concluded that the outcomes of this study suggested that administering high concentration, full-spectrum ashwagandha root had an anti-stress effect with little to no side effects and an overall positive improvement on self-assessed quality of life.⁸  Researchers admitted that the study was small and the duration was limited, thus recommending studies with larger sample sizes and longer treatment periods are warranted.⁸

In a randomized, double-blind, placebo-controlled study, researchers examined the effect of ashwagandha on generalized anxiety disorder (GAD).⁹ The study consisted of 86 patients diagnosed with GAD, divided into two groups.⁹ The treatment group received four grams of ashwagandha root in granule form three times a day for 60 days while the placebo group received four grams of placebo for 60 days.⁹ Researchers measured a variety of symptoms including tension, fear, insomnia, difficulty with concentration/memory, depressed mood, sensory and muscular complaints, and anxiety.⁹ Results  showed that on all measures both groups experienced highly significant improvement but on all measures except one, there was no significant difference between the treatment and placebo groups.⁹ Researchers stated that anxiety was the only factor that improved in a superior manner with the administration of ashwagandha compared to the placebo.⁹ However, researchers commented, “On the whole, despite having insignificant statistical difference in both the groups, Group A, Ashwagandha (Withania somnifera) granules, showed a better percentage improvement than Group B (placebo). Ashwagandha (Withania somnifera) granules have shown superior results in the management of GAD as compared to placebo granules. Hence, the alternate hypothesis is accepted i.e. Ashwagandha (Withania somnifera) is effective in the management of Generalized Anxiety Disorder”.⁹

Pratte and colleagues performed a systematic review of several of the above-mentioned studies and made several interesting comments regarding the outcomes and validity of the studies.¹⁰ Across the five studies fitting inclusion criteria, researchers reported consistently positive study results regarding the use of ashwagandha to lessen stress and anxiety.¹⁰ However, researchers illuminated multiple study limitations in all of the reports reviewed including researcher bias, small sample sizes, short duration of trials and lack of researcher blinding.¹⁰ Further, according to Cochrane criteria, none of the studies achieved low risk-of-bias rating.¹⁰ Therefore, researchers concluded that though the results of the studies showed ashwagandha’s superiority over placebo, the outcomes must be taken with cautionary optimism.¹⁰

Side Effects and Risk

Though ashwagandha has been reported as a “possibly safe” plant for ingestion, it is important to investigate the overall side effect profile as well as the potential risk of use.¹ Some state that large doses of the plant may produce stomach upset, diarrhea and vomiting and further, that the long-term safety of its use has not yet been determined.¹ In addition, some caution has been recommended for those suffering from various diseases, based upon possible risks associated with interactions of medications or disease progression.¹ Others suggest ashwagandha may lower blood sugar levels or interfere with medications in diabetic patients, decrease blood pressure in people with hypotension, irritate the gastrointestinal tract, increase immune system activity in autoimmune patients, slow down the central nervous system thus causing complications with anesthesia, and increase thyroid hormone levels in those suffering from thyroid disorders.¹ These potential side effects and risks present the importance of using ashwagandha with discretion. For the current analysis, the studies previously reviewed shed further light on the side effect profile of this so-termed medicinal plant.

When human clinical trials were reviewed in regard to the anxiolytic effects of plant-based medicines, researchers concluded that ashwagandha was well tolerated by subjects and did not produce any heightened levels of adverse effects when compared to placebo.⁴

Of the 98 subjects who participated in a double-blind, randomized, placebo-controlled study on the effect of ashwagandha on chronically stressed humans, researchers reported that adverse effects were absent in all subjects, including those who dropped out of the study.⁵ Researchers clarified further, stating that the lack of adverse effects was observed regardless of dosage or frequency of administration.⁵

When an ethanolic extract of ashwagandha was used in a double-blind, placebo-controlled study involving patients diagnosed with anxiety disorders, the plant was not only well tolerated by participants but adverse side effects were comparable to those demonstrated in participants using placebo.⁶ Researchers stated a percentage of subjects dropped out of the study, reportedly due to adverse effects, yet fewer came from the ashwagandha group when compared to the control group.⁶ Further, adverse effects were observed early in the study and were reportedly easily managed by way of dosage adjustment.⁶  Of additional importance, though abrupt withdrawal was initiated at six weeks, no withdrawal symptoms appeared in the participants, thus leading researchers to state ashwagandha’s superiority to the conventional anxiolytic drugs such as benzodiazepines, tricyclic antidepressants, and buspirone which oftentimes have adverse withdrawal effects.⁶

In a randomized study performed to determine the effectiveness of naturopathic care on measures of anxiety compared to standardized psychotherapy treatment, researchers looked at the benefit of several treatments including ashwagandha.⁷ Researchers did not observe any serious adverse reactions from the dispensation of ashwagandha.⁷

When used in a prospective, randomized, double-blind, placebo-controlled study, high concentrations of full-spectrum extract of ashwagandha root produced favorable results with few side effects.⁸ Follow-up interviews were conducted over the phone on days 15, 30, and 45 to evaluate treatment compliance as well as evaluation of any adverse reactions.⁸  Additional safety and efficacy evaluations were performed on day 60.⁸ Out of the 61 subjects reviewed, only six adverse events were reported, a minimal number particularly when compared to the five adverse events reported in the placebo group.⁸ Reported side effects were nasal congestion, constipation, cough/cold, drowsiness and decreased appetite in the treatment group compared to dry mouth, fatigue, fever, headache, abdominal pain, diarrhea and tremors in the legs in the control group.⁸ Researchers further stated that all adverse events were mild and “no known mechanisms relate these adverse events to the study drug”.⁸

Researchers in a randomized, double-blind, placebo-controlled study examined the effect of ashwagandha on generalized anxiety disorder (GAD) in 86 patients previously diagnosed with this disturbance. Outcomes of the study indicated a lack of adverse side effects for those ingesting ashwagandha over the course of the investigation.⁹

Conclusions

From the above-reviewed studies, it appears that ashwagandha may have beneficial potential for aiding in the reduction of symptoms pertaining to stress and anxiety. It is important to note that in some studies, though positive benefit was observed, the favorable outcomes were not deemed statistically significant.

A point worth mentioning is the fact that despite the varied nature of administration, it did not appear that the manner in which the plant was distributed (i.e. tablet form, pill form, granule form), the dosage or the frequency of ingestion significantly influenced the outcomes of the plant’s efficacy rating. Of significant note is the lack of reported adverse side effects as well as the lack of negative feedback in regard to withdrawal symptoms. Though side effects, adverse reactions and withdrawal symptoms may have been underreported, there did not appear to be evidence pointing to their frequency or significantly problematic nature. These factors point to the possible positive nature of ashwagandha in those dealing with symptoms of anxiety and heightened stress without the added concern of contracting adverse reactions.

As previously mentioned, limitations did exist across all of the studies, giving rise to caution when drawing conclusions yet the preponderance of the evidence points to the prospective but cautionary use of ashwagandha as an effective way treat symptoms associated with stress and anxiety. However, it is important to recognize that though the use of ashwagandha to ameliorate unpleasant symptoms may provide relief, it serves primarily as a symptom manager. In other words, the underlying cause of the anxiety and stress does not get addressed at the core if surface symptoms are simply alleviated. Therefore, if this plant is used to aid in the process of treatment, it may be advisable to utilize it as a complementary modality rather than a primary method of therapy.

Clinical Note

Within a practice setting, I would likely veer away from recommending such a supplement due to the potential for it becoming a crutch and thus preventing clients from delving into the real issues at hand. However, I am not sure I would spend a whole lot of time talking a client out of using such a product if he/she is set on using it, namely because it does not appear that ashwagandha presents significant risks or side effects. If a client chose to utilize this supplement as a symptom reliever, I would be sure to explain the research behind it, my reservations regarding its use, and ultimately the importance and necessity of the client making a personal and informed decision about it.

References

1.      WebMD. Ashwagandha. Available at: https://www.webmd.com/vitamins/ai/ingredientmono-953/ashwagandha. Accessibility verified August 4, 2018.

2.      Michigan Medicine: University of Michigan. Ashwagandha. Available at: https://www.uofmhealth.org/health-library/hn-2039005#hn-2039005-uses. Accessibility verified August 4, 2018.

3.      Duke JA. In: CRC Handbook of Medicinal Herbs. 2^nd ed. Boca Raton, FL: CRC Press; 2002: 41-42.

4.      Sarris J, McIntyre E, Camfield DA. Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence. CNS Drugs. 2013; 27(4): 301-19.

5.      Auddy B, Hazra J, Mitra A, Abedon B, Ghosal S. A standardized withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study. Journal of the American Nutraceutical Association. 2008; 11(1): 50-56.

6.      Andrade C, Aswath A, Chaturvedi SK, Srinivasa M, Raguram R. A double-blind, placebo-controlled, evaluation of the anxiolytic efficacy of an ethanolic extract of withania somnifera.  Indian Journal of Psychiatry. 2000; 42(3): 295-301.

7.      Cooley K, Szczurko O, Perri D, et al. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS ONE. 2009; 4(8): 1-10.

8.      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 Journal of Psychological Medicine. 2012; 34(3): 255-262.

9.      Khyati S, Anup T. A randomized double-blind placebo-controlled study of ashwagandha on generalized anxiety disorder. International Ayurvedic Medicine Journal. 2013; 1: 1–7.

10.   Pratte MA, Nanavati KB, Young V, Morley CP. An Alternative Treatment for Anxiety: A Systematic Review of Human Trial Results Reported for the Ayurvedic Herb Ashwagandha (withania somnifera). Journal of Alternative and Complementary Medicine. 2014; 20(12): 901-908.