Accurate Education – Ashwagandha

Ashwagandha (Withania somnifera)

 

Ashwagandha is an herbal medicine that has been used for centuries in the practice of Ayurvedic medicine in India’s Hindu culture to combat and reduce stress, improve sleep quality and enhance general wellbeing. It is believed to promote “youthful vigor” by enhancing muscle strength, endurance, and overall health. Ashwagandha is gaining attention in western medicine as research supports the use of Ashwagandha in the management of stress and anxiety.

 

Ashwagandha is also popularly known as Winter Cherry. In India the plant is known by different vernacular names like Punir (Hindi), Ashvaganda (Bengal, Bombay), Aksan (Punjab), Amukkira (Tamil) and Tilli (Marathi). The practitioners of the traditional system of medicine in India regard W. somnifera as the “Indian Ginseng.”

 

 

  

See also:

 

Terms:

Adaptogens

Adaptogens are defined as substances that increase attention and endurance in fatigue, and reduce stress-induced impairments and disorders related to the neuro-endocrine and immune systems.

 

 Ayurveda

According to Ayurveda, the traditional medical system of India, doshas are a combination of characteristics based on a five-element philosophy that drive our mental and physical tendencies. When the doshas, or functional principles, are out of balance in quality or quantity, wellbeing is adversely affected and symptoms occur. Research suggests that symptoms of mind-body imbalances in Ayurveda are associated with western assessments of psychological states.

 

 

 

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Ashwagandha

Ashwagandha (Withania somnifera (L.) Dunal) is a small shrub that grows in dry regions of South Asia, Central Asia, and Africa. It has been used as an herbal medicine for centuries in Ayurveda, an ancient Hindu system of medicine. Over 50 chemical constituents have been identified in the various parts of the ashwagandha plant, including various compounds and flavonoids that have antioxidant activity.

 

Ayurveda

Ayurveda, the traditional medical system of India, recognizes doshas, or functional principles. It is the combination of the doshas characteristics based on a five-element philosophy that drives mental and physical well-being. When the doshas are out of balance in quality or quantity, well-being is impaired and symptoms occur. Research suggests that some of the diagnoses established in Ayurveda overlap in many ways with western medical diagnoses, particularly related to anxiety and stress. As such, traditional Ayurveda treatment may offer benefit in the management of anxiety and stress.

  

In Ayurveda, disharmony among the doshas are managed by dietary and lifestyle interventions, including herbs, diet, massage, meditation, and yoga, paralleling contemporary western integrative medical management of anxiety and stress. Herbal treatments with Ashwagandha are frequently used to treat conditions associated with stress and anxiety in Ayurveda. 

  

How Is Ashwagandha  Used?

Ashwagandha has been used for many different conditions but there is not enough research yet available to judge whether it is effective for any of them and this website strongly encourages evidence-based medical practice.

 

That being said, there is a great deal of experience with centuries of use in Ayurvedic medicine that has sparked a great deal of western interest in the potential benefits of Ashwagandha. It is used for anxiety, stress, bipolar disorder, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), trouble sleeping, arthritis, back pain, fibromyalgia, hiccups, asthma, bronchitis, and Parkinson’s disease. Chronic treatment with Ashwagandha extract in animal studies demonstrated reduced development of tolerance to morphine.

 

Ashwagandha has also been reported to improve mental well-being and eating behaviors through its adaptogenic properties along with maintaining the normal endocrinological balance in conditions of stress. It has been reported to maintain an adequate range of testosterone, enhance cognitive abilities in people with mild cognitive impairment, and boost cardiorespiratory endurance.

 

The active constituents of plant (Withaferin A, Sitoindosides VII–X) are reported to have an antioxidant activity which may contribute at least in part to the reported anti-stress, immunomodulatory, cognition facilitating, antiinflammatory and anti-ageing properties. Ashwagandha is also reported to modulate the GABAergic [(γ-amino-butyric acid (GABA)] receptor system which may account for its anti-anxiety and sleep promoting properties.

 

 

Adaptogens and Stress Management

Stress is defined as any disturbance –extreme cold or heat, psychological stress, sleep deprivation, work overload, physical trauma, as well as toxic exposure- that can trigger the stress response.  During the 1950’s the idea of using herbal medicinal plants to increase stamina and survival in harmful environments was developed, and a new concept of “adaptogens” was introduced by the toxicologist Lazarev to describe compounds which could increase “the state of non-specific resistance” in stress. An adaptogen can be defined as “a substance that improves responses to stress and helps the body adapt by normalizing physiological processes in times of increased stress.” Prolonged stress triggers the body’s stress response system which is comprised of the hypothalamic-pituitary-adrenal (HPA) axis, the part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation. This concept was based on Hans Selye’s theory of stress and general adaptation syndrome, which has three phases: stage 1: alarm; stage 2: resistance; and stage 3: exhaustion.

 

The initial, short-lived first phase (the alarm phase) is the body’s normal fight-or flight response to danger which is characterized by elevated cortisol levels. The next phase, the resistance phase, allows the body to continue buffering extended stress exposure, long after the initial fight-or-flight response has resolved. The hormones cortisol and DHEA are released by the adrenals and support the “resistance” reaction. However, prolonged stress burdens the system, creating an imbalance in cortisol and DHEA production which can result in mental and physical fatigue, nervous tension, irritability and poor memory – features characteristic of stage 3.

 

Adaptogens enhance non-specific resistance to stress and decrease sensitivity to stressors, which results in stress protection, and prolong the phase of resistance (stimulatory effect). Instead of exhaustion, a higher level of equilibrium (homeostasis) is attained. The higher it is, the better the adaptation to stress.

 

Adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly by increasing tolerance to mental exhaustion and enhanced attention. They reduce stress-induced impairments related to the neuro-endocrine and immune systems. The adaptogen Ashwagandha is believed to exert its stress-protective effects primarily by regulating homeostasis via several mechanisms of action associated with the hypothalamic pituitary adrenal (HPA) axis.

 

Adaptogens also work by modulating key mediators of the stress response, such as cortisol, nitric oxide (NO), and molecular chaperones (e.g. the “stress-sensor” protein Hsp70) by regulating as many as 88 genes associated with adaptive stress response pathways. Adaptogens activate cellular adaptive systems by inducing the expression of genes, including those that encode neurohormones and neurotransmitters.  These adaptogen-activated cellular pathways are associated with neuroinflammation and neuropathic pain as well as stress-induced and aging-related disorders such as chronic inflammation, cardiovascular diseases, neurodegenerative cognitive impairment, diabetes and other metabolic disorders and cancer.

 

Rhodiola rosea, another adaptogen, provides multiple benefits likely reflecting more than one mechanism of action. Rhodiola acts on another part of the stress-system, namely, the sympatho-adrenal-system (SAS), that provides a rapid response mechanism mainly to control the acute, immediate reaction to a stressor.

 

A recent study shows  Rhodiola to have inhibitory effects on the monoamine oxidases (MAO-A and MAO-B). Monoamine oxidase (MAO)-A regulates the metabolic breakdown of the monamine neurotransmitters (adrenaline, noradrenaline, dopamine and serotonin) in the central nervous system and peripheral tissues. The mechanism by which Rhodiola is believed to function as an adaptogen is its ability to preserve levels of the monamine neurotransmitters. Norepinephrine, for example is thought to play a role in the body’s stress response and helps to regulate sleep, alertness, and blood pressure.

 

Because stress is known to impair the immune system,  adaptogens proposed stabilization of the stress response also supports the assertion that adaptogens improve the immune response during times of high stress. While a review of the pharmacologic basis for adaptogen’s activity is beyond the scope of this review, the reader may turn to:

Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity – 2010.

 

The botanicals commonly attributed to be adaptogens include Siberian Ginseng (Eleutherococcus senticosus), Schisandra berry (Schisandra chinensis), licorice root, Rhodiola rosea, Bacopa and Ashwangandha. Ashwagandha is most commonly used as a general tonic and as an “adaptogen” to help the body cope with daily stress.

 

Studies of Ashwangandha as an Adaptogen in the Management of Stress

A 2012 study of 61 patients taking 300 mg twice a day of high-concentration full-spectrum Ashwagandha root extract (KSM-66 by Ixoreal Biomed) assessed the level of stress, depression, anxiety and general well-being of individuals using three different sets of stress scales and serum cortisol levels.  Compared to placebo, greater reductions were seen in the scores for all three subsets in the Ashwagandha group after 60 days of treatment.

 

In the Ashwagandha group, by Day 60 there was a significant reduction in scores corresponding to all of the item subsets: 77% for the “Depression” item-subset, 75.6% for the “Anxiety” item-subset, 64.2% for the “Stress” item-subset. In contrast, in the placebo-control group, the corresponding reductions in scores were much smaller: 5.2%, – 4.3% and 10.4%, respectively. After 60 days of treatment, serum cortisol levels showed a reduction of 27.9% from baseline in the Ashwagandha group, while in contrast, a reduction of 7.9% was observed in the placebo-control group.

 

The authors concluded that their findings suggest that high-concentration full-spectrum Ashwagandha root extract safely improves an individual’s resistance towards stress and improves self-assessed quality of life.

   

Ashwagandha for Anxiety & Sleep

Although limited, research supports the benefit of Ashwagandha for the management of anxiety and insomnia. Positive anxiolytic effects of Ashwagandha in adults with generalized anxiety disorder have been identified in clinical studies.  Pharmacological studies have confirmed that Ashwagandha has anxiolytic and sleep-inducing properties. Most of the clinical studies on the anxiety benefits of Ashwagandha have been conducted in India so the impact of diet, economic conditions, and daily occupation may have had an influence on therapeutic outcomes as compared to western cultures.

 

A 2009 study performed in Canada compared a Naturopathic anxiety treatment regimen consisting of Ashwagandha (300 mg twice a day), dietary counseling, deep breathing relaxation techniques and a standard multi-vitamin versus a traditional psychotherapy model consisting of psychotherapy and matched deep breathing relaxation techniques, and placebo. The Naturopathic model proved to be safe and effective with superior benefit over standardized psychotherapy in the treatment of mild to severe generalized anxiety.

 

A systematic review was published in 2014 that evaluated Ashwagandha as a treatment for anxiety and stress. The review was limited to only five publications that met the standards of their review and the results were of moderate quality. The general finding among the studies was that Ashwagandha produced favorable results when compared with placebo. The one study that approached, but failed to achieve, significance for its primary outcome measure of anxiety relief had the shortest trial duration and smallest sample size. The remaining four trials showed significant differences between Ashwagandha and placebo, supporting Ashwagandha’s benefit for anxiety and stress relief.

 

A recent 2019 study evaluated the effects of Ashwagandha (240 mg of an Ashwagandha extract, Shoden) over 60 days in adults with mild stress. Results revealed significant improvements in anxiety which were also associated with reductions in morning cortisol and DHEA-S. The Ashwagandha was well tolerated with no significant adverse events.

 

Another 2019 study evaluating 250 mg/day and 600 mg/day of Ashwagandha (KSM-66 Ashwagandha root extract) also showed significant reduced stress measures including lower serum cortisol levels. Although the 250 mg/day dose of Ashwagandha extract did not result in improved anxiety, the 600 mg/day dose was effective for anxiety.  Over the eight weeks in this study there was also a significant improvement in sleep quality, with the 600 mg/day dose of Ashwagandha more effective than the 250 mg/day dose.

 

Another 2019 study that focused on the sleep benefits of Ashwagandha extract (300 mg twice a day of KSM-66 Ashwagandha root extract) found it to be well tolerated and that it improves sleep quality and sleep onset latency (time required to fall asleep) in patients with insomnia.

  

In all the studies that have evaluated the anxiolytic effects of Ashwagandha, varying Ashwagandha extracts, using different extraction techniques and standardization methods, were used. Overall, anxiety and sleep benefits of Ashwagandha have been established; however, the relative safety and anxiolytic potency of the different extracts vary. Future trials will be required to clarify these variables.

  

Neuroinflammation and Ashwagandha

Neuroinflammation is implicated in the evolution of chronic pain and is the focus of current research into means of reducing the incidence of the progression of acute to chronic pain. It is characterized by activation of immune cells (glial cells and astrocytes) in the nervous system that release various inflammatory chemicals like cytokines, proteases, reactive oxygen, and nitrogen species. Pharmacological studies have suggested that Ashwagandha has anti-inflammatory and neuroprotective  properties, suggesting their potential for use in chronic pain. Preclinical animal research published in 2018 supports the benefit of Ashwagandha in reducing neuroinflammation, although additional research is needed.

 

 

Side Effects and Safety

Ashwagandha is generally considered safe when taken orally for short-term use, but the safety of long-term  use of Ashwagandha is not known. The studies have demonstrated only mild side effects including loss of appetite and sedation. Large doses of Ashwagandha might cause stomach upset, diarrhea, and vomiting. Ashwagandha may be sedating.

 

Drug Interactions

Immunosuppressants

Because Ashwagandha may increase the immune response, taking Ashwagandha with medications purposed to decrease the immune system might decrease the effectiveness of these medications. Medications are used to suppress the immune system in conditions such as auto-immune disorders, rheumatoid arthritis, lupus, psoriasis and cancer. Commonly used immune suppressants include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids (glucocorticoids), and others. Do not take Ashwagandha if you are prescribed any of these medications without discussing it with your prescribing physician.

 

Sedatives

Due to its sedative properties, Ashwagandha should be used with caution when also taking sedatives such as sleeping medicines, antidepressants and anxiolytic drugs like benzodiazepines.

 

Diabetic medications

There is preliminary evidence suggesting that Ashwagandha might lower blood glucose levels thus Ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of low sugar.

 

Thyroid hormones

Preliminary research suggests that Ashwagandha increases thyroid hormone synthesis and secretion. In one clinical study, Ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline. Combined use of Ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects.

 

Ashwagandha Products

Ashwagandha is available in both capsule forms of powdered Ashwagandha root and liquid extracts such as:

  1. KSM-66 (Ixoreal Biomed) Available in different commercial products
  2. Ashwagandha Extract (Klaire Labs) Available at: Accurate Clinic’s Supplement Store

  

Additionally, Ashwagandha is available in combination products including:

  1. Adapten-All (Orthomolecular)

 

Dosing

Ashwagandha is commonly used in doses from 250 mg/day to 300-600mg twice daily to improve symptoms of stress, anxiety and sleep.

 

How Does Ashwangandha Work?

Constituents

The major biochemical constituents of Ashwagandha are a class of constituents known as withanolides. The withanolides have a structural resemblance to the active constituents present in the plant Panax ginseng known as ginsenosides, and because of this Ashwagandhais is also referred to as “Indian Ginseng.” 

 

So far as many as 50 or more constituents have been isolated from Ashwagandha. The various alkaloids include withanine, withaferin A, somniferine, somnine, somniferinine, withananine and others. Withaferin A has been recently reported to be inhibitor of angiogenesis and thus protective in certain types of cancers. Two glycowithanoloids (sitoindoside IX or sitoindoside X) possessed antistress activity and augmented learning acquisition and memory retention in animal studies.

Neuro-Endocrine Effects

Under normal conditions without high stress, a regulatory negative feedback system within the hypothalamic-pituitary-adrenal (HPA) axis maintains normal cortisol and DHEA levels. In stress, including anxiety and depression, disturbances in HPA axis activity lead to excess cortisol and DHEA secretion. Although high levels of DHEA are often associated with increased health and longevity, within the context of stress, DHEA elevation may be an indicator of an increased stress response (or HPA activity). Increased DHEA- S secretion has been shown to follow acute stress exposure and it is higher in adults with posttraumatic stress disorder.  As such, elevated DHEA (along with cortisol) may be a marker of increased stress while acute reduction may, therefore, be a sign of stress reduction.

 

Anti-Anxiety Effects

The anxiety benefits of Ashwagandha may be due to several mechanisms. The mechanism of action most commonly proposed for  Ashwagandha is its stabilizing effect on the HPA axis where it becomes less reactive to stressors. It has been shown that Ashwagandha reduces morning cortisol and DHEA-S levels suggesting Ashwagandha has a moderating effect on HPA axis activity in stressed adults.

 

Other possible mechanisms of Ashwagandha’s anxiolytic effects may be its antioxidant and anti-neuroinflammatory effects. Inflammation and oxidative stress are increased during times of high stress, and higher levels have been demonstrated in adults with depression and anxiety. Additionally, Ashwagandha has been shown in preclinical studies to influence GABAergic and serotonin activity, which have anxiolytic and antidepressant effects.

 

References:

Adaptogens – Overviews

  1. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity – 2010
  2. Relationships Among Classifications of Ayurvedic Medicine Diagnostics for Imbalances and Western Measures of Psychological States – An Exploratory Study – 2019
  3. Stimulating Effect of Adaptogens- An Overview With Particular Reference to Their Efficacy Following Single Dose Administration – 2005
  4. A preliminary review of studies on adaptogens – comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide – 2018
  5. Novel Molecular Mechanisms for the Adaptogenic Effects of Herbal Extracts on Isolated Brain Cells Using Systems Biology – 2018
  6. Adaptogens Exert a Stress-Protective Effect by Modulation of Expression of Molecular Chaperones – 2009
  7. Understanding Adaptogenic Activity- Specificity of the Pharmacological Action of Adaptogens and Other Phytochemicals – 2017′
  8. Adaptogens in Mental and Behavioral Disorders – 2013
  9. Evidence-based Efficacy of Adaptogens in Fatigue, and Molecular Mechanisms Related to Their Stress-Protective Activity – 2009
  10. Chemistry and Pharmacology of Syringin, A Novel Bioglycoside – A Review – 2015

 

AshwagandhaOverviews

  1. Scientific Basis for the Therapeutic Use of Withania somnifera (Ashwagandha) – A Review – 2000
  2. Withania somnifera an Indian ginseng. – 2008

Ashwagandha – Adaptogen

  1. 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 – 2012
  2. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity – 2010
  3. A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha (Withania somnifera) in Aging, Overweight Males – 2019
  4. Relationships Among Classifications of Ayurvedic Medicine Diagnostics for Imbalances and Western Measures of Psychological States – An Exploratory Study – 2019
  5. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract – 2019

Ashwagandha – Anxiety

  1. 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 – 2012
  2. Dietary and botanical anxiolytics – 2012
  3. Naturopathic Care for Anxiety – A Randomized Controlled Trial – 2009
  4. An Alternative Treatment for Anxiety – A Systematic Review of Human Trial Results Reported for the Ayurvedic Herb Ashwagandha (Withania somnifera) – 2014
  5. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults – A Double-blind, Randomized, Placebo-controlled Clinical Study – 2019
  6. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract – 2019
  7. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety – A Double-blind, Randomized, Placebo-controlled Study – 2019

Ashwagandha – Cognition & Neurodegenerative Disorders

  1. Scientific Basis for the Use of Indian Ayurvedic Medicinal Plants in the Treatment of Neurodegenerative Disorders- Ashwagandha – 2010
  2. Effects of Ashwagandha (Roots of Withania somnifera) on Neurodegenerative Diseases – 2014
  3. Efficacy and Safety of Ashwagandha (Withania Somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions – 2017
  4. Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation – 2019
  5. A Systematic Review of the Clinical Use of Withania Somnifera (Ashwagandha) to Ameliorate Cognitive Dysfunction – 2020

  

Ashwagandha – Neuroinflammation

  1. Withania Somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation – 2018

Ashwagandha – Obsessive Compulsive Disorder (OCD)

  1. Evaluation of the Efficacy of Withania Somnifera (Ashwagandha) Root Extract in Patients With Obsessive-Compulsive Disorder- A Randomized Double-Blind Placebo-Controlled Trial – 2016

 

Emphasis on Education

 

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