Ashwagandha: What It Is and The Science Behind It's Health Benefits

You may have heard or read of this ayurvedic herb before - either online, on the news, or in discussions had by those around you, yet never looked into it much until now. What is this herb that has been touted to have a wide range of health benefits, and which claims have some merit to them? In this article, we’ll cover the health benefits of Ashwagandha in detail, covering the research that has been done on this adaptogenic herb. But first, a little history as to why this plant has caught the attention of medical and health researchers in the first place.

Historical Origins

Ashwagandha (Withania Somnifera) is a popular herb in both Traditional Chinese medicine and Ayurveda (traditional Indian medicine) - the latter being where it is most widely used and the most likely to have used it first, as it is more native to regions in India, with ancient historical texts documenting it’s usage predating Chinese ones, and that it was never codified directly into TCM principles (although formal integration into TCM is being worked on in modern times). It is likely that Ayurvedic doctors shared their knowledge with Chinese scholars as time passed, and thus the herb itself began to be grown in the Chinese region as well as medical usage there increased too.[1,2] In these traditional medical practices, the main components of the plant that were used are the root, followed by the fruit, and it had a wider use of applications; from wound care to fertility regulation. Over time though, as medicine advanced, scientists began to look into this herb due to its historical medical usage and anecdotal evidence of helping in some ailments. 

Most Popular Health Claims

Now onto the harder science: which purported benefits are the most likely to be true based on current research into Ashwagandha?

The main biologically active components in Ashwagandha that have been identified to have potential benefits are: alkaloids (naturally occurring organic compounds that mostly contain basic nitrogen atoms and which have significant physiological actions on humans), steroidal lactones (carboxylic acids - like amino acids - that are esters and have steroidal effects), and withanolides (primarily steroidal lactones mostly found in the nightshade family, of which Ashwagandha is part of, but also other novel kinds are included as well) -  each having different mechanisms of action which affect the body in varying ways. I’ll list out the most popular claims which show possible and general health benefits documented with Ashwagandha intake, and any observed or proposed mechanisms of action.

Stress, Anxiety, and Depression

Although no single compound has been as of yet identified as a cause of stress and anxiety reduction behind Ashwagandha use, a full-spectrum extract of the root of Withania Somnifera (KSM-66), containing a standardized level of 5% withanolides minimum and insignificant amounts of Withaferin A cytotoxin, has shown in multiple studies to lower negative mood levels pertaining to stress, anxiety, and depression. The first - a randomized double blind, placebo controlled study - consists of a rather small sample size of 61 adults (originally 64, but 3 participants did not follow through) with the following demographics and baseline parameters:

They were split into 2 groups, with one given a placebo and one given 300mg of the KSM-66 extract for 60 days. Before and after, they were given 3 psychometric tests (Perceived Stress Scale or PSS, General Health Questionnaire 28 or GHQ-28, and the Depression Anxiety Stress Scale, or DASS), as well as had their serum cortisol levels measured, since serum cortisol is a frequently used biological marker for stress. The before and after data was then compared to show percent changes in both groups in negative mood reduction or increase. As the following graph shows, there was a significant negative mood reduction in the group taking the Ashwagandha root extract[3]:

Although this shows there is a strong adaptogenic potential in Ashwagandha root lowering stress levels and improving mood, it is a small study. Yet, a systematic review of five human trial results (including the one just used here) show that all five conclude that “W(ithania) S(omnifera) intervention resulted in greater score improvements (significantly in most cases) than placebo in outcomes on anxiety or stress scales”[4], and a newer 2016 study that looked into the effects of chronic stress reduction and body weight management, found similar results as well[5], reinforcing evidence that there are compounds in Ashwagandha root which lowers stress and aid in improving mood. However, as discussed later on in the article, the reason that Ashwagandha may do so might be due to a domino effect, in which Ashwagandha’s effects on improving sleep then causes improved mood due to increased amount of - and quality of - sleep.

Effects on Brain Function

There are identified compounds in both Ashwagandha root and leaves which do affect brain cells - however, it seems these compounds are most effective / only effective when extracted and isolated from the plant in high concentrations.[B1] This is because despite the evidence of these compounds working when doing on brain cells in vitro, when a clinical trial is run, there tends to be poor results.[B2] However, to reiterate,that does not mean that there is nothing in Ashwagandha that has no effect. There are identified neuroprotective phytoconstituents that cause key pharmacological effects in cells related to brain disorders - primarily Alzheimer's, Parkinson's, Schizophrenia, addiction, and amyotrophic lateral sclerosis. The current issue is that the mechanistic pathway and metabolic process in the body is still unknown. What is known is that simply eating the plant parts don’t seem to cause the same effects as those seen in vitro, and ingesting extracts results in mixed and/or poor results. Concentrations of dosage for efficacy are also uncertain at the moment as well, adding difficulty on setting up clinical trials. 

Ultimately, more research is needed not in whether certain phytoconstituents in Ashwagandha have an effect on brain cells - that’s been demonstrated in both animal models and in vitro on human cells, with effects such as stimulating dendrite growth to observed neuroprotective effects against oxidation. What needs to be studied more is how these compounds, and perhaps even overall Ashwagandha itself as well, works in the body. Once the metabolism of Ashwagandha is better understood, then perhaps it will be easier to understand the mechanistic pathway of these specific phytoconstituents (and whether the compounds can pass the blood-brain barrier), and from there finally the best modes of transportation can be determined to try out in clinical trials (if possible). Such is the way of science, to build upon the works of others while making educated guesses based on data collected until a certain conclusion can be found, shown, and proven. On the bright side, at least currently there have been no observed toxic effects of Ashwagandha on brain cells despite certain compounds being mildly cytotoxic elsewhere in the body.

Effects on Sleep

Ashwagandha has long been used as a sleep aid in Ayurvedic medicine, and multiple very recent studies show strong evidence that it does, indeed, help with improving sleep. Currently, it’s benefits for sleep have the strongest evidence of all claims, with multiple double-blind, randomized, placebo controlled studies showing the same correlations (and a larger scale study currently in the works due to the findings of previous studies). It’s also thought that this sleep aiding effect may be somehow connected with the findings that Ashwagandha reduces anxiety as well. Best of all, there is currently no evidence that using the herb as a sleep aid causes dependency, unlike other sleep aids currently available. Now let’s take a more detailed look at this research.

The study we’ll cover the most is one that was done to determine efficacy and safety of Ashwagandha root extract in insomnia and anxiety.[S1]This was a randomized, double-blind, placebo-controlled study where a total of 60 patients were randomly divided into two groups: test (40 people) and placebo (20 people). 2 Participants however, 1 from each group, did not finish the study in its entirety and were omitted.

In this study, they used a capsule containing a high concentration of full-spectrum Ashwagandha root extract at 300 mg, and a placebo that was an identical capsule containing starch. Both treatments were given twice daily for 10 weeks. Sleep actigraphy (a method of monitoring human rest/activity cycles where a sensor, typically a bracelet of sorts, is worn that detects and records things like movement and light. In this case, the study used a sensor made by Respironics Philips) was used for the assessment of sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE) and wake-after-sleep onset (WASO). Other assessments that were done included a sleep log, mental alertness on rising, sleep quality, the Pittsburgh Sleep Quality Index, and the Hamilton Anxiety Rating Scale.

As shown in the charts below, the averaged trend of the SOL, SE, and WASO parameters show a statistically significant improvement in how long it took participants taking the extract in how fast they fell asleep (sleep onset latency), how restful the sleep was (sleep efficiency recorded by actigraphy test), and reduced time staying awake while/if waking at night before fully waking and rising in the morning (Wake Time After Sleep Onset):

The  Pittsburgh Sleep Quality Index scores also showed some positive results, with Ashwagandha extract users having an increased total sleep time than placebo users:

And the Hamilton Anxiety Rating Scale also shows a notable reduction in anxiety as well (which other studies into Ashwagandha’s effect on anxiety support, as mentioned in the previous section):

This does suggest the possibility however that the reason Ashwagandha reduces anxiety and may improve overall mood is due to its effect on improving sleep, rather than by directly affecting anxiety and such itself directly.

This isn’t the only randomized, double-blind, placebo-controlled study which has results that suggest that Ashwagndha extract can improve sleep. One published only months after the previously mentioned one showed similar results, although it was done on the elderly and for 12 weeks.[S2] Both studies’ results seem to suggest that longer term use of the extract results in further improved scores, although why that is, remains unknown as of yet.

Of course, despite the strong evidence currently found, it will still be years of research before there is enough evidence to see mainstream high quality Ashwagandha derived components on store shelves, as these studies are using full spectrum extracts and are small in scale and time frame (but as mentioned earlier, a larger scale study is currently underway), although one animal study done on mice claims to have identified the exact ingredient in Ashwagandha that induces sleep: triethylene glycol.[S3] The study does need further replication and verification however, and just because triethylene glycol induces sleep in mice does not mean the same thing will happen in humans - it could be some other component in Ashwagandha which is what plays a factor in sleep instead. Either way, it is with no doubt that one should look forward to what future Ashwagandha studies further uncover when it comes to its effects on sleep improvement.

Thyroid Affection

There are still few studies on the subject, but it is known for certain that yet unspecified compounds in Ashwagandha root can affect the thyroid (although how the mechanism of action works is still unknown). Studies done previously in mice had shown the root having a very notable effect on thyroid stimulation[6], and therefore human trials have since then begun recently. 

One of the first, a randomized, double-blind, placebo controlled trial done Sudbhawana Hospital, Varanasi, India, was done with 50 subjects (aged 18-50) which had elevated serum thyroid stimulating hormone (TSH) levels, in which 25 received 600mg KSM-66 daily and 25 received a placebo of starch daily (4 participants withdrew consent however - 2 from each group, leaving the total sample size at the end at 46). They had their Serum TSH, serum triiodothyronine (T3), and thyroxine (T4) levels evaluated before starting the trial, at 4 weeks, and at 8 weeks after starting the trial. In all the patients that took the KSM-66 root extract, TSM serum levels had significantly increased and T3 and T4 serum levels had significantly decreased compared to the placebo group - effectively normalizing measure serum thyroid indices during the 8 week trial.[7] Despite the small sample size, this gives strong evidence that Ashwagandha root could potentially have therapeutic effects for thyroid disorders. Yet, until the mechanisms of action are known, and the compounds which affect the thyroid are identified, takingtoo much Ashwagandha root can cause thyrotoxicosis as well (although this case helps further cement that there is indeedsomethingin Ashwagandha that does stimulate the thyroid to release more hormones).[8]

As the old saying goes, “the dose makes the poison”, and any medicine, adaptogenic or not, can be dangerous in high amounts. Fortunately, it seems it takes a pretty high dose before Ashwagandha root has any severe effects such as thyrotoxicosis, and low enough doses do not seem to be causing any noticeable negative effect on normal, healthy thyroids. That does mean that due to the known effects Ashwagandha root can have on thyroids, consult your doctorbeforetaking any if you are already taking medication for your thyroid.

Effects on the Immune System

There is actually very little research on humans in any form on Ashwagandha’s effects on the immune system. Instead, nearly all research into the effects of Ashwagandha on the immune system have been on animal models - primarily mice and, interestingly enough, broiler chickens (turns out there’s significant evidence it helps chickens resist certain diseases by strengthening their gut microbiome)[ii1]. In these mice studies, there’s been strong evidence that Ashwagandha leaf extract does invoke a significant immunostimulatory response (both in vivo and in vitro), even in mice that had been given immunosuppressants[ii2]. Whether this would translate into humans is yet to be studied and seen, but as of now it is too early to say with any certainty if Ashwagandha could have an effect on the immune system in humans. As a precaution, talk with your medical care provider if you take any immunosuppressants (such as those given after organ transplant) before taking any Ashwagandha supplements.

Anti-inflammatory Effects in Joint Cartilage 

Osteoarthritis is a disease that disproportionately affects women which has mixed results in relation to relief when it comes to current medical treatments in pain management and prevention.[10] Fortunately, recent research has shown the possibility of Ashwagandha possessing analgesic, anti-inflammatory and chondroprotective (protective of chondroblasts, which are progenitor cells that make new cartilage matrix) effects.[11,12]

In this case, an aqueous extract high in withanolide glycosides (manufactured by Sensoril) made from both the leaves and root of the plant was used in a randomized, double-blind placebo study. 60 patients were split into three groups and given either 250mg or 125mg of the extract, or a placebo, all given twice daily. Assessment of their condition was done by using a modified Western Ontario and McMaster Universities Arthritis (WOMAC) index , Knee Swelling Index (KSI), and Visual Analogue Scale (VAS) at baseline and at the end of 4, 8, 12 weeks. In all test results, improvement was shown in the two groups which received the extract, with the group that received 250mg showing a statistically significant improvement, as can be seen in the following charts[13]:

The mechanism of action for this is still uncertain, but it is believed that the beneficial effects actually come from a byproduct of the body metabolizing the Ashwagandha extract

       WOMAC

KSI

The mechanism of action for this is still uncertain, but it is believed that the beneficial effects actually come from a byproduct of the body metabolizing the Ashwagandha extract.

Effects on Cardiovascular Health

There are promising newer studies that have been done in the last decade that show Ashwagandha has a strong potential at benefiting the cardiovascular system. Researchers began looking more closely into Ashwagandha’s effects on the cardiovascular system after noticing effects related to said system were showing up in unrelated studies. Research into Ashwagandha’s effects on cardiovascular health are still relatively new though, so the mechanism of action is still unknown, and there have been no identified compounds of affection as of yet identified either. The studies that have been done however do show a good correlation that Ashwagandha can aid in two things: cardiorespiratory endurance and hypertension. I’ll cover the findings on each one in detail as subtopics.

Hypertension

A study on 51 individuals (aged 40-70) who had a history of hypertension were split into two groups (I and II) were given 2g Ashwagandha dried root powder every morning for 91 days. All participants were and had been before the study on specialized diets designed to prevent blood pressure from increasing. Group I was instructed to take the Ashwagandha root powder with milk (the traditional way it is taken in Ayurvedic medicine, to see if milk enhances the effects of Ashwagandha root as purported), while group II took it with water.[ht1] The following averaged graphs show a decent decrease in blood pressure, with a significant decrease in diastolic blood pressure in the group that took the Ashwagandha root powder with milk:

These results indicate that there is potential to use Ashwagandha to medically control diastolic blood pressure in the future, and that a daily low dose of Ashwagandha root powder can aid in maintaining blood pressure in those who are slightly hypertensive. More peer review is still needed to confirm these findings, although they are also supported by mice studies looking into Ashwagandha’s effects on blood pressure.[ht2]

Cardiorespiratory Endurance

A prospective, double-blind, randomized, and placebo-controlled study evaluated the efficacy of Ashwagandha rootextract (not powder in this case) in enhancing cardiorespiratory endurance and improving physical performance in 50 healthy male and female athletic adults aged between 20-45. This exploratory study lasted 12 weeks, during which the subjects visited the research center after 4, 8, and 12 weeks. All enrolled subjects underwent a complete physical examination at all visits, though no blood tests were taken (VO2max tests were performed however). The results showed statistically significant improved performance in the administered 20 minute shuttle run tests, albeit only on weeks 8 and 12.[ht3] Interestingly, unlike the study done with the powdered form of the root, there were no significant changes in blood pressure. I would like to note however that unlike the hypertension study, none of these subjects had a history of hypertension or of ever taking medication for hypertension, and they were all relatively young and healthy. Another study (which also looked at a different herb as well) done on 40 young adults with an average age of around 20 also found similar cardiorespiratory endurance performance improvement as well, having similar results[ht4], supporting the findings of the first study mentioned.

Effects on Male Fertility

There have been a few studies done which give some evidence that Ashwagandha root extract (primarily KSM-66) may improve fertility in men by increasing sperm count and motility. A review in the role of withania somnifera shows that multiple studies have observed improvement in fertility in both mice and men, and has a proposed general mechanism of action for how compounds in the root may work in humans:

It’s proposed that the main reason that Ashwagandha can improve fertility is due to a reduction of seminal lipid peroxidation due to specific antioxidants contained in the plant, in combination with GABA-mimetics stimulating a chain response in the hypothalamic-pituitary-gonadal (HPG) axis that leads to a slight increase in male testosterone. Ultimately, more research and replication studies are required to establish what compounds lead to the observed effects to establish an exact mechanism of action and to confirm that the mechanism of action is correct, and from there to figure out exactly what dose is needed to best improve fertility in men, as some studies achieved effects with high doses Ashwagandha root which are unsustainable in long term use due to possible negative effects from certain withanolides (such as Withaferin-A) can have by causing cytotoxic build up.[9] Still, low, inconsistent doses of the root could probably help in maintaining sperm health in men thanks to the seminal antioxidant properties which have been found - but again, more needs to be done to confirm this is true with certainty.

Effects on Female Sexual Health

It is already known that Ashwagandha has some effect on women’s reproductive system due to certain withanolides having aborticant effects if taken in the long term or in very high concentrations. Despite that, it is possible to get around the negative effects Ashwagandha can cause on reproduction itself by using extracts which are low in the withanolides that negatively affect pregnancy and conception. This is important because there is some preliminary evidence that in the right concentrations, Ashwagandha root extract can improve a woman's sexual health, including women with differing forms of female sexual dysfunction (FSD). 

One  double blind, placebo-controlled, randomized pilot study[FS1] that was done in order to determine the safety and efficacy of using an Ashwagandha root extract in improving women’s sexual function using the Female Sexual Function Index (FSFI) - which checks desire, arousal, lubrication, orgasm, pain and satisfaction levels - as well as the Female Sexual Distress Scale (FSDS). The pilot study’s participants had to meet the following criteria:

• Female subjects aged 21–50, in a steady heterosexual relationship for over a year, previously or presently engaged in sexual function for several years.
• Have a male partner with a score of “not impotent” or “minimally impotent” on a Single-Question, Self-Report of Erectile Dysfunction (Massachusetts Male Aging Study).
• Have a baseline starting total score of <26 on the FSFI and a baseline starting total score of >11 on FSDS.
• Have been diagnosed with the conditions for FSD with one or more of the following disorders:
• hypoactive sexual desire disorder (HSDD)
• female sexual arousal disorder (FSAD)
• female orgasmic disorder (FOD)
• combined genital and subjective arousal disorder
• Willing to engage in sexual intercourse with an intent-to-attain orgasm at least twice/week.
• Willing to use a condom as a contraceptive measure (no hormonal contraceptives)

50 participants were divided into two randomized groups and given either a placebo or KSM-66 Ashwagandha root extract at 300mg twice per day for 8 weeks. Assessments were done at the start, at week 4, and at week 8. The results for each domain of the FSFI are given below, along with the mean score of the FSDS:

Percent improvement in the Mean FSFI Score for “pain” domain in ashwagandha root extract treated group and placebo treated group.

As you can see, statistically significant differences can be seen in all domains, showing there is a positive effect on Ashwagandha extract on female sexual health. No adverse effects were also reported during the testing either, making it safe to take this formulation of extract at the dosage that was administered. It is important to keep in mind however that this is only a single small sample pilot study, and a large scale study still needs to be done to see if these results will still hold true. The positive news on the other hand is that the p-values are low, meaning it would be less likely to see significant deviation if the study was reproduced on a larger scale.  

Conclusion and Contraindications

There is plenty of evidence that Ashwagandha can bring about a multitude of health benefits due to a plethora of bioactive compounds found in the plant, and it certainly establishes itself as an adaptogen in regards to its ability to regulate stress. However, it is exactly because this plantactuallycan affect the body that there are a few contraindications to note:

• As stated previously, consult your doctor before taking Ashwagandha root supplements of any kind if you are already taking a thyroid medication - otherwise it would be as you were takingtwomedications for your thyroid at once.
• Don’t take very high doses of Ashwagandha in any amount and respect its medicinal properties. Just as you wouldn’t take 5 grams of acetaminophen/paracetamol at once, or 4,000mcg of Vitamin A in a day, don’t take more Ashwagandha than would be recommended, either.
• Talk with your doctor if you are taking medication for hypertension (such as beta blockers or calcium channel blockers) as there is evidence (as stated previously) that Ashwagandharoot may somewhat lower blood pressure (especially diastolic pressure). Extracts taken from the leaves of Ashwagandha may be safe however, as there is no current strong evidence that leaf extracts affect blood pressure the same way the dried root powder and possibly root extracts do.
• Due to Ashwagandha’s potential sleep improving effects, it may work synergistically with other sleep aids, so keep that in mind - otherwise you might have a really groggy day afterwards.
• DO NOT TAKE Ashwagandha root powder if pregnant, or trying to get pregnant - there is evidence that Withaferin A, and other withanolides found in Ashwagandha, can have abortifacient effects and cause miscarriage. Even in Ayurvedic applications, the plant was not given to pregnant women. High quality rootextracts that have extremely low amounts of cytotoxic withanolides seem to be safe to use however in proper dosages (typically not reaching or exceeding 1000mg daily).

If you do not fall into those categories however, Ashwagandha is generally safe to use at the right doses. Remember, adaptogens and herbal medicine and supplements can have health benefits on the body, but only when respected and taken as they should be. Even in traditional Ayurvedic medicine, these powerful herbs were given with consideration of the person’s condition. As long as Ashwagandha is taken in low, supplemental doses, it should impart its health benefits to you. As always, take advantage of the benefits nature gives such as those with adaptogens, but do not abuse of it. As long as you respect the herb, it will respect you. Hopefully this article delving into the health benefits of Ashwagandha makes you appreciate the power of nature, and helped you learn how to properly add adaptogens into your life, and how they can help you stay healthy and energized!

References:

1: Charak Samhita 6000BC, author. Charaka translation into English: Translator: Shree Gulabkunverba Ayurvedic Society. Jamnagar, India: 1949

2: Forman, Michael & Kerna, Nicholas. (2018). Merging Ayurvedic Ashwagandha with Traditional Chinese Medicine Part 1. Foundation in Ashwagandha: Physiological Effects, Clinical Efficacy, and Properties. 10.29011/2577-2201/100033.

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3: Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). 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, 34(3), 255. doi: 10.4103/0253-7176.106022

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Citations for topics added in August 2020 Update

[S1]Langade, D., Kanchi, S., Salve, J., Debnath, K., & Ambegaokar, D. (2019). Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study.Cureus. doi:10.7759/cureus.5797

Retrieved from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827862/

[S2]Kelgane, S. B., Salve, J., Sampara, P., & Debnath, K. (2020). Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study.Cureus. doi:10.7759/cureus.7083

Retrieved from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096075/

[S3]Kaushik, M. K., Kaul, S. C., Wadhwa, R., Yanagisawa, M., & Urade, Y. (2017). Triethylene glycol, an active component of Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction.Plos One, 12(2). doi:10.1371/journal.pone.0172508

Retrieved from:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172508

[B1]Wadhwa, R., Konar, A., & Kaul, S. C. (2016). Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts.Neurochemistry International, 95, 109-118. doi:10.1016/j.neuint.2015.09.001

Retrieved from:https://www.sciencedirect.com/science/article/abs/pii/S0197018615300437

[B2]Shah, N., Singh, R., Sarangi, U., Saxena, N., Chaudhary, A., Kaur, G., . . . Wadhwa, R. (2015). Combinations of Ashwagandha Leaf Extracts Protect Brain-Derived Cells against Oxidative Stress and Induce Differentiation.Plos One, 10(3). doi:10.1371/journal.pone.0120554

Retrieved from:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120554

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