Ashwagandha: Is It Really The King Of Adaptogens?

Written by Andy Mobbs
featured image for article on ashwagandha, a seneca nootropic ingredient

Ashwagandha is so much more than just an exotic name, it’s actually a powerful nootropic and adaptogen in its own right. In this article, you’ll find out how it regulates cortisol levels, its effect on cognitive and thyroid function, and more!

What is Ashwagandha?

Ashwagandha has been used for 6000 years in Ayurveda which is the traditional system of medicine in India. And if people have been using something for 6000 years, then that’s generally a pretty good sign.

In fact, it’s used for a whole range of issues, such as an aphrodisiac, anti-constipation, anti-anxiety, anti-insomnia, anti-goiter, anti-inflammatory, and anti-aging (1).

Whilst ashwagandha is sometimes called the Indian Ginseng, its name in Sanskrit actually means “smell of the horse”. This is a reference to both its smell being like a horse and its ability to give you the power of a stallion as well!

So far, there have been over 30 different active ingredients isolated from ashwagandha. The most beneficial ingredient is thought to be a class of chemicals known as the ‘withanolides’ (2).

How does ashwagandha work as an adaptogen?

Ashwagandha is best known as an adaptogen. An adaptogen is something that helps our body to normalize cortisol levels. Cortisol is a strong anti-inflammatory and our ‘dealing with stress’ hormone. The more stress we are under, the more cortisol we need to produce to deal with that stress. So cortisol follows stress, be that physical inflammation, infection or injury, or psychological trauma.

When doctors talk about giving patients ‘steroids’ to reduce inflammation and immune system activity, they are actually talking about giving synthetic cortisol (e.g dexamethasone). This is very different from the ‘steroids’ athletes may use which are metabolites of testosterone. Both are referred to as steroids since both cortisol and testosterone are made from cholesterol, and cholesterol-based hormones are known as steroid hormones.

Whether our cortisol levels are adequate or not is a little more complicated than just measuring whether they are high or low. For example, they could be high, but not actually high enough to deal with the stress we are under, which can happen when we face chronic inflammation or chronic psychological tension.

In fact, although many people believe we should be aiming to lower cortisol to deal with stress, actually increasing cortisol when it’s already high, but not high enough to deal with our inflammation levels, can make people feel a whole lot better.

And this is the beauty of adaptogens, they can increase cortisol when it needs to be increased, and decrease when it needs to be decreased.

The Hypothalamus Pituitary Adrenal Axis

To properly understand cortisol, we need to understand the Hypothalamus Pituitary Adrenal Axis (HPA axis). This is the system through which cortisol is produced, and it’s controlled by the hypothalamus. The hypothalamus is only a small part of our brain, but it acts as a control center and controls our response to stress, growth, metabolism, reproduction, water conservation, blood pressure, lactation, and childbirth. It receives feedback from the rest of the body in the levels of hormones circulating, but also in molecules called cytokines (3).

Cytokines are special molecules that fulfill a number of roles in embryonic development, but also in signaling inflammation and stimulating immune system activity. They are vital, for example, in fighting off infections. They are also vital in giving the hypothalamus feedback on what is going on in the rest of the body. If we are under stress, the levels of certain cytokines will increase which signals to the hypothalamus to stimulate the HPA axis to deal with this stress.

In the HPA axis, the hypothalamus produces a hormone called CRH (Cortical Releasing hormone), which then goes to the pituitary gland in the brain. Based on the levels of CRH it receives, the pituitary then releases ACTH (Adrenocorticotropic hormone) which travels to the adrenals and tells them to produce cortisol.

stress response system

However, this connection between the hypothalamus and the pituitary is also responsible for the production of other hormones. Most notably, these are the sex hormones testosterone, estrogen, and progesterone as well as thyroid hormones. These hormones are produced in 2 more axes called the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-thyroid (HPT) axis.

In the hypothalamic-pituitary-gonadal (HPG) axis, instead of CRH, the hypothalamus produces Gonadotropin-releasing hormone (GnRH), which goes to the pituitary. Then the pituitary produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH) instead of ACTH. LH and FSH act on the testis or ovary to produce testosterone or estrogen and progesterone.

hypothalamic pituitary gonadal (hpg) axis

In the hypothalamic-pituitary-thyroid (HPT) axis the hypothalamus releases thyroid releasing hormone (TRH) instead of CRH. TRH acts on the pituitary to stimulate the release of thyroid-stimulating hormone (TSH) instead of ACTH. TSH stimulates the release of T4 and T3 from the thyroid. T4 and especially T3 are the active thyroid hormones that stimulate activity in our cells.

HPT axis

However, when the hypothalamus is upregulating activity in the HPA axis to deal with stress, this takes priority over activity in both the HPG and the HPT axes, and they are downregulated. This means we produce fewer sex hormones and fewer thyroid hormones when cortisol is high. This is something that is deep-wired into our evolution. Cortisol is about dealing with stress in the present moment, and that from an evolutionary perspective is the most important thing for our survival.

For example, whilst producing sex hormones is important for feeling good and for proper cognitive function, if our lives are in danger, it’s not a great idea to have a desire to go and look for a mate and to try to have babies. This is also true for the thyroid, if we have an infection or a lot of inflammation, the production of thyroid hormone will be downregulated so that we want to go and lie down in the cave so we can recover.

This is where ashwagandha can help. It can reduce the need for cortisol by reducing inflammation or our perception of psychological stress and therefore our resilience to stress. So when we reduce our stress, we feel better, our brains function better, our immune systems function better and we can also increase thyroid output and the production of things like testosterone or estrogen (4). This, in turn, creates more feelings of well-being.

Also, conversely, when we are not producing enough cortisol to deal with the level of inflammation, it can increase cortisol levels so that we can gain control of it. Unfortunately today, many people suffer from hypothyroidism or infertility. Very few doctors or practitioners are considering whether the problem lies in too much stimulation to the HPA axis.

Ashwagandha Benefits: What is it good for?

Here are 8 benefits of taking ashwagandha:

Benefit #1 – Stress Resistance

Several studies in rats have demonstrated the stress resilience abilities of ashwagandha. For example, Archana and Namasivayam took a group of rats and put them through a forced cold water swimming test. This is a test where the rats are put into plastic cylinders filled with water, which forces them to swim.

There were 2 groups in the study, one treated with ashwagandha and one that wasn’t. In the group that wasn’t treated with ashwagandha, they found significant increases in immune activity as well as a corresponding increase in cortisol levels. However, in the group that was given ashwagandha, there was only a small increase in immune activity and cortisol levels, and the rats were able to swim for almost double the amount of time.

Also, Vitamin C levels were higher in the adrenals of the rats given ashwagandha, indicating there was less oxidative stress in the ashwagandha-treated adrenals. In other words, taking ashwagandha meant stress is much less stressful (5).

These results were repeated in a study on humans in India that used 64 subjects, who were all free of physical or psychological diseases, but who felt chronically stressed. They all took 300mg of ashwagandha root twice a day for 60 days. At the end of the study period, the researchers found that their cortisol levels were significantly reduced. The participants also found that they felt better and had a higher quality of life after taking ashwagandha (6).

Benefit #2 – Regulation of the Sex Hormones

A recent study on overweight, aging males from 40 – 70 years old found that after receiving 300mg of Ashwagandha extract for 16 weeks the men had increased testosterone levels of 14.1% (7).

Another study using 5 grams of Ashwagandha in 75 infertile men for 3 months found that they had higher levels of testosterone, LH, FSH, and improved sperm counts and sperm quality (8).

In women, one study found that women who took 300mg of Ashwagandha twice a day for 2 months had a significant increase in arousal, orgasm, lubrication, and sexual frequency (9).

Also, a study on 51 menopausal women found that Ashwagandha helped to normalize estrogen and reduced hot flashes, balanced mood, and improved sleep issues, irritability & anxiety (10).

Benefit #3 – Improvement in Thyroid function

Cortisol and Metformin were given to type 2 diabetic mice which caused hypothyroidism. However, treatment with ashwagandha was able to restore thyroid hormone to normal levels (11).

A further study in 50 people with subclinical hypothyroidism, which means low thyroid function without the diagnosis of a specific disease, found that after 8 weeks of treatment with 600mg of ashwagandha daily, T4, T3, and TSH levels had all normalized (12).

Benefit #4 – Neuroregeneration and Alzheimers

Researchers are able to create neurodegeneration, i.e kill off brain cells and synapses in the brains of rats by injecting amyloid-beta proteins. These proteins form the amyloid plaques that are very common in the brains of Alzheimer’s patients.

After injecting amyloid-beta protein, Zhao et al found that ashwagandha was able to stimulate axonal growth (13). Kuboyama et al found that ashwagandha was able to stimulate regrowth of axons, dendrites, and synapses (14).

In fact, ashwagandha has actually shown that it can target the precursors to amyloid proteins to stop them from forming, which could potentially prevent the development of Alzheimer’s (4).

It’s worth noting that these studies are never done on humans, as the researchers need to dissect the brains after the experiments to analyze the neurons.

Benefit #5 – Regenerating Neuronal Injuries

Ashwagandha can also help nerve cells to regenerate themselves after either physical or chemical injury. The main reason why people are left paralyzed after accidents is because specialist cells called ‘astrocytes’ secrete chemicals that stop the cut nerve axons from regenerating. Normally astrocytes provide protection for neurons and supply them with nutrients, but when spinal cords are cut they are actually ‘overprotective’ and stop the regeneration process.

However, work by Nakayama and Tohda has shown that taking a withanoside (one of the active components in ashwagandha) intravenously for several weeks induced axonal growth and allowed for recovery of motor function in mice (15).

Benefit #6 – Antioxidant Defence

Ashwagandha has also been shown to be able to up-regulate NRf2, which is a transcription factor, i.e something that causes certain genes to become active, that leads to the production of the body’s main antioxidant Glutathione (4).

Ashwagandha has also been shown to stimulate the production of the body’s other main antioxidants Super Oxide Dismutase and Catalase (16).

Benefit #7 – Acetylcholine, Brain Derived Neutrophic Factor, and Memory Improvement

Scopolamine is a drug that can induce loss of muscle movement and memory loss in humans and animals. It works by inhibiting acetylcholine receptors in the body which are vital for movement, memory, and learning. It also causes the inhibition of Brain Derived Neurotrophic Factor (BDNF), which is vital for cognitive function.

An ashwagandha extract has shown that it can prevent the effects of scopolamine by inhibiting the effect of scopolamine by activating acetylcholine receptors, so scopolamine can’t reach them. Ashwagandha also increased levels of BDNF (17).

These benefits make ashwagandha an effective nootropic or memory enhancer! Each serving of our Seneca Nootropic includes 500mg of ashwagandha root powder, along with 17 other research-backed nootropic ingredients like B vitamins, Lion’s Mane, Bacopa Monnieri, and Ginkgo Biloba!

Related article: What are nootropics?

Benefit #8 – Antidepressant and Anti-anxiety effects

A study by Bhattacharya et al in mice showed that an ashwagandha extract has a similar anti-anxiety effect to the benzodiazepine lorazepam which acts on GABA receptors in the brain. In the same experiment, they also found that the extract had the same anti-depressant effect as the antidepressant imipramine (18).

A further study by Candelario et al also found that ashwagandha could activate the GABA receptors of rat brains (19).

What’s the proper ashwagandha dosage?

Most studies have looked at doses of ashwagandha around the 250mg to 500mg range, although some have gone much higher. Some people also choose to supplement with larger doses as it seems to have few side effects. However, higher doses should always be built up gradually.

Conclusion

Ashwagandha is an effective adaptogen that can help to normalize cortisol levels as well as sex hormones and thyroid hormones. It can also protect the brain and promote healthy brain function. Hopefully, in the future, we will see more studies in humans, looking specifically at its effects on cortisol, fertility, and hypothyroidism.

However, whilst much is already known about its potential in these areas, ashwagandha’s effects on cognitive decline and dementia, as well as a role in spinal injuries possibly along with stem cell treatments are even more exciting. The question as always is where the funding would come from for these studies.

References

(1) An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda, Narendra Singh, Mohit Bhalla, Prashanti de Jager, and Marilena Gilca, Afr J Tradit Complement Altern Med. 2011; 8(5 Suppl): 208–213.

(2) Singh, P., Guleri, R., Singh, V., Kaur, G., Kataria, H., Singh, B., Kaur, G., Kaul, S.C.,Wadhwa, R., Pati, P.K., 2015. Biotechnological interventions in Withania somnifera (L.) Dunal. Biotechnol. Genet. Eng. Rev

(3) Olga J G Schiepers 1, Marieke C Wichers, Michael Maes, Cytokines and major depression, Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):201-17.

(4) Wadhwa, R., Konar, A., Kaul, S.C., Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts, Neurochemistry International (2015)

(5) Archana R, Namasivayam A, Antistressor effect of Withania somnifera, J Ethnopharmacol. 1999 Jan; 64(1):91-3.

(6) 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 Jul;34(3):255-62.

(7) Adrian L. Lopresti, Peter D. Drummond, and Stephen J. Smith, A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha (Withaniasomnifera) in Aging, Overweight Males, American Journal of Men’s Health, March-April 2019: 1–15

(8) Mohammad Kaleem Ahmad, Abbas Ali Mahdi, Kamla Kant Shukla, Najmul Islam, Singh Rajender, Dama Madhukar, Satya Narain Shankhwar, Sohail Ahmad, Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males, Fertility and Sterility, 2010

(9) Swati Dongre, Deepak Langade, Sauvik Bhattacharyya, Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study, Biomed Res Int. 2015;2015:284154.

(10) Mansi B Modi 1, Shilpa B Donga, Laxmipriya Dei, Ayu, Clinical evaluation of Ashokarishta, Ashwagandha Churna and Praval Pishti in the management of menopausal syndrome 2012 Oct;33(4):511-6.

(11) Rameshwar Jatwa, Anand Kar, Amelioration of metformin-induced hypothyroidism by Withania somnifera and Bauhinia purpurea extracts in Type 2 diabetic mice, Phytother Res. 2009 Aug;23(8):1140-5.

(12) Ashok Kumar Sharma, Indraneel Basu, Siddarth Singh, Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial, J Altern Complement Med. 2018 Mar;24(3):243-248.

(13) Zhao, J., Nakamura, N., Hattori, M., Kuboyama, T., Tohda, C., Komatsu, K., 2002. Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem. Pharm. Bull. (Tokyo) 50, 760-765.

(14) Kuboyama, T., Tohda, C., Komatsu, K., 2005. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br. J. Pharmacol. 144, 961-971.

(15) Nakayama, N., Tohda, C., 2007. Withanoside IV improves hindlimb function by facilitating axonal growth and increase in peripheral nervous system myelin level after spinal cord injury. Neurosci. Res. 58, 176-182.

(16) Kumar, P., Singh, R., Nazmi, A., Lakhanpal, D., Kataria, H., Kaur, G., 2014. Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity. Biomed. Res. Int. 2014, 182029.

(17) Konar, A., Shah, N., Singh, R., Saxena, N., Kaul, S.C., Wadhwa, R., Thakur, M.K., 2011, Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells, PLoS One 6, e27265.

(18) Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study, S K Bhattacharya , A Bhattacharya, K Sairam, S Ghosal, Phytomedicine. 2000 Dec;7(6):463-9.

(19) Manuel Candelario, Erika Cuellar, Jorge Mauricio Reyes-Ruiz, Narek Darabedian, Zhou Feimeng, Ricardo Miledi, Amelia Russo-Neustadt, Agenor Limon , Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors, J Ethnopharmacol. 2015 Aug 2;171:264-72. doi: 10.1016/j.jep.2015.05.058. Epub 2015 Jun 9.