Immunomodulating Activity of an Extract from Ashwagandha: Implications for Treatment of Parkinson’s

“The mind, in addition to medicine, has powers to turn the immune system around.” Jonas Salk

“As you begin to heal the inner you, you alter your immune system.” Wayne Dyer

Introduction: The current blog post is focused on reviewing an immunomodulating action of an extract from Ashwagandha. Furthermore, I will comment on the use of Ashwagandha for treating Parkinson’s. I recently reviewed Ashwagandha in this blog (click here to read it).

For centuries, Ashwagandha has been used in Ayurvedic medicine for rejuvenation, stress relief, and treating Parkinson’s. Recently, I reviewed the concept that Parkinson’s could be considered an autoimmune disorder (“Parkinson’s and Autoimmunity,” click here to read blog post). Also, Tharakan et al. (2021) described the immunomodulating activity of an extract from Ashwagandha.

Tharakan, Ajit, Himanshu Shukla, Irin Rosanna Benny, Matthan Tharakan, Lekha George, and Santhosh Koshy. “Immunomodulatory effect of Withania somnifera (Ashwagandha) extract—a randomized, double-blind, placebo controlled trial with an open label extension on healthy participants.” Journal of Clinical Medicine 10, no. 16 (2021): 3644.

“Every act of kindness on your part is a boost to your own immune system.” Marianne Williamson

What is an Immunomodulatory Substance? Let’s begin by reminding one about how to describe the immune system and the components of immunity given in the schematic below:

Immunomodulators are substances that either activate or inhibit the immune system response, specifically immunostimulants, and immunosuppressants. Therefore, substances that ‘turn on’ the immune system could augment the body’s battle against an invading microorganism. Likewise, compounds that ‘turn off’ the immune system could potentially assist in attenuating the body;’s assault on itself in autoimmune disorders. This is further described in the graphic below:

“A belly laugh increases the ability of your immune system to fight infections.” Elizabeth Taylor

The Complexity of Ashwagandha: Rasayana is a Sanskrit word that means path (ayana) of essence (rasa). In Ayurvedic medicine, Rasayana refers to lengthening lifespan and invigorating the body (for more details, see the following in Wikipedia). Ashwagandha is considered part of the Rasayana treatment regimen.

Ashwagandha is a complex medicinal substance from the plant Withania somnifera. The component of Ashwagandha with an immunomodulating function is thought to be withanolide glycosides; see the image below for the structure. Withanolides are a large group of naturally occurring steroids. The amount of withanolides in Ashwagandha varies from company to company; evidently, many Ashwagandha supplements are standardized to contain 5-10% withanolide glycosides.

For a comprehensive review article about Ashwagandha, please see Singh et al. (2011), cited below:

Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-13. doi: 10.4314/ajtcam.v8i5S.9. Epub 2011 Jul 3. PMID: 22754076; PMCID: PMC3252722.

To read further about the properties of withanolide glycosides from Ashwaganda, please see this review article by Ha et al. (2022):

Ha JW, Yu JS, Lee BS, Kang DM, Ahn MJ, Kim JK, Kim KH. Structural Characterization of Withanolide Glycosides from the Roots of Withania somnifera and Their Potential Biological Activities. Plants (Basel). 2022 Mar 13;11(6):767. doi: 10.3390/plants11060767. PMID: 35336649; PMCID: PMC8954635.

“If we could do something that enhances the body’s immune system here on Earth, it would be a tremendous step forward in the fight against disease and cancer and other things.” John Glenn

Immunomodulating Activity of Withanolide from Ashwagandha: There have been prior studies to determine the test tube immunomodulating effect of the withanolide from Ashwagandha; however, the product had not been extensively studied in humans. Thus, Tharakan et al. (2021) explored the potential for the withanolide Ashwagandha extract to possess immunomodulating activity in humans:

•They tested 24 adult male and female volunteers, and they were all considered healthy.
•The study was a placebo-controlled, double-blinded, parallel-arm, and single-center pilot study. The study had a 30-day treatment plan. After the 30-day test period, the control group was given the extract for an additional 30-days. The investigators and subjects were blinded to the identity of the products and control capsules.
•The produce given to the test patients was withanolide glycosides prepared by ethanolic powder extract of dried roots and leaves of Withaniasomnifera. The test product contained 60 mg of Ashwagandha and 21 mg of withanolide glycosides, with the control capsule containing rice powder. One capsule per day was the dose for the study.
•The test group of volunteers showed a significant increase in the immunoglobulins tested. The placebo group did not exhibit any changes in immunoglobulin content.
•The test group also showed a significant increase in levels of these cytokines tested, interleukin-4 (IL4) and interferon-g [gamma (IFNg)]. The placebo group showed no change.
•Several immune cells population also showed significant increases in cells expressing CD45+, CD3+, CD4+, CD8+, CD19+, and natural killer (NK) cells. Interestingly, the placebo group showed significant decreases in all cells except CD19+ and NK cells.
•In the test group, there were significant increases in platelet count, neutrophil count, lymphocytes, and leukocytes; however, red blood cells, eosinophils, basophils, monocyte, hematocrit, and hemoglobin remained the same. Likewise, the placebo group showed significant increases in platelets and a significant reduction in lymphocytes; the other Complete Blood Count (CBC) was unchanged.
•There were no adverse effects reported.

“Immune system will heal itself.” Rhonda Byrne

Implications for Ashwagandha and the Withanolide Glycoside Fraction for Immunomodulation: The results of the pilot study in a small sample of humans results in an immunostimulatory action for Ashwagandha and its purified fraction of withanolide glycoside. The data found for the test product gave an enhanced synthesis of IL-4, which would upregulate TH2-type T-lymphocytes, coupled with an increase in INF-g synthesis, suggesting a combined effect of upregulation. In addition, the results from the work of Tharakan et al. (2021) verified portions of prior work.

This pilot study needs to be expanded, and further data involving molecular biology tools/probes for various immune processes should be performed. The authors also do not fully account for the changes in the control volunteers and the seemingly total up-regulation of many hematopoietic features studied. However, if these studies are repeated and expanded, and the results verified, they would support the role of withanolide glycosides as immunostimulants. As gleaned from their results, elements of the innate and adaptive immune systems are upregulated by this component from Ashwagandha (see drawing below).

“The difference between destruction of the immune system and stimulation of the immune system is an interpretation.” Deepak Chopra

Implications for Ashwagandha and the Withanolide Glycoside Fraction for Treating Parkinsons: If a given Ashwagandha preparation contains 5-10% by weight of withanolide, then a capsule of 500 mg of Ashwagandha would have 25-50 mg of withanolide. This range of withanolide exceeds the amount tested here.

Recently, I reviewed the recent field of immunological studies/reviews on Parkinson’s being considered an autoimmune disease. Although there are numerous ways for Parkinson’s to begin, growing evidence supports and links Parkinson’s as an autoimmune disorder. For a further review, see the blog post entitled “Parkinson’s and Autoimmunity.”

As mentioned above describing the type of immunomodulating substances, it is clear that the withanolides in Ashwagandha are immunostimulatory. In autoimmune disorders, one would not necessarily take an immunostimulant for someone’s immune system activated and attacking self-antigens (i.e., you).

Autoimmune disorders consist of a broad array of disease conditions/states. There are several FDA-approved drugs to treat autoimmune diseases, whereby the vast majority suppress elements of the immune system. However, there are instances where an immunostimulant has provided relief from an autoimmune disorder by stimulating a specific aspect of the immune system. Significantly, the goal of currently used immunomodulating medications has improved outcomes in many medical situations and slowed disease progression.

“Hope, purpose and determination are not merely mental states. They have electrochemical connections that affect the immune system.” Norman Cousins

Ashwagandha and Parkinson’s: There are several ways to interpret all of this information regarding the centuries-old extract from Withania somnifera known as Ashwagandha and the autoimmune disease aspect of Parkinson’s. Three thoughts come to mind:

#1, From an old nursery rhyme, “If ‘ifs’ and ‘buts’ was candies and nuts, we’d all have a merry Christmas.”

#2, Heisenberg’s uncertainty principle (in quantum mechanics) is any of a variety of mathematical inequalities asserting a fundamental limit to the accuracy with which the values for specific pairs of physical quantities of a particle, such as position and momentum, can be predicted from their starting conditions (click here for further information).

#3, “Be careful about reading health books. You may die of a misprint.” Mark Twain

If you believe Parkinson’s is an autoimmune disorder, perhaps taking Ashwagandha (containing a substantial fraction of withanolides) could be detrimental to your condition by upregulating one’s immune system. However, hundreds and hundreds of years of people-with-Parkinson’s (PwP) have been treated with Ashwagandha, so what’s up? Many of my former students would tell me that their grandmother would add Ashwagandha powder into warm milk, and they would drink this mixture every morning. Is this Ashwagandha powder served in warm milk like the capsules I swallow with water?

My logic for taking Ashwagandha was related to its ability to reduce stress/manage anxiety and improve cognitive function. I have been taking 650 mg of Ashwagandha daily, and according to the manufacturer, it contains 2% withanolides (i.e., 13 mg withanolide glycosides per capsule). Whether or not this small amount of withanolides would be modulating my immune system is the real question. Although I believe in the historical significance and treatment strategies of Ayurvedic medicine, until I understand the autoimmune link between Parkinson’s and the immunomodulating function of withanolide in Ashwagandha, I have stopped taking Ashwagandha.*

*Please be reminded of the blog’s medical disclaimer statement/policy (click here).

“The most powerful force to maintaining a good immune system is the power of positive thinking and not allowing yourself to be unnecessarily drained emotionally by worries and fears.” Frederick Lenz

Cover Photo Image by Pexels from Pixabay

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