What is stress? And how do adaptogens help combat it?

Adaptogens are described as “any of various natural substances used in herbal medicine to normalize and regulate the systems of the body.”¹ Particularly, adaptogens help to regulate our stress response.

But what is stress - biologically and physiologically - and what are adaptogens doing to combat it?

Stress can be a number of things, but it is most commonly considered a systemic result of the actions of a few structures in the brain and body in response to stimuli. It is important to remember that these stimuli can be external and internal, small and large, physical and psychological. The measure of severity of a stressor is often not its perceived intensity, but the intensity of the reaction of an individual’s nervous system.



The most immediate stress response is one that we’re all familiar with: the fight-or-flight response. This is the reason you feel that rush of adrenaline when someone or something frightens you. The fight or flight reaction is the direct result of the sympathetic nervous system. The sympathetic nervous system is part of the autonomic nervous system, which handles a wide range of processes in your body and mind that are not under your voluntary control. The sympathetic nervous system primes your body for immediate, life or death danger (e.g. think of the times our biological ancestors woke up to a tiger in their cave).


In response to stressful stimuli, the sympathetic nervous system uses the hypothalamus, a key brain structure in the stress response, to call for the production of norepinephrine. This neurotransmitter kick starts the body’s rapid stress response, which does things like dilating your pupils, increasing your heart rate, shunting blood to your muscles, deactivates your brain centers in charge of thinking while activating the centers for emotion and memory, and priming your immune system to fight off infection in case you get hurt.²

While the sympathetic nervous system response to stress is fast, it doesn’t last very long. So, in order to make sure you are prepared in case you encounter a similar situation soon after, the body couples its immediate nervous system response with a longer-term, endocrine response.

The endocrine system manages your body’s hormones, which are systemic messengers that lead to lasting changes throughout the body. This stress endocrine response is guided primarily by the HPA axis, or hypothalamic-pituitary-adrenal axis.

The response starts in the hypothalamus, which acts to connect the brain and body by processing new sensory information and then talking to the pituitary gland to release hormones. When the pituitary gland receives a Corticotropin Releasing Factor [CRF] signal from the hypothalamus, it releases Adrenocorticotropic Hormone [ACTH]. The ACTH flows into the bloodstream and then acts on the adrenal glands, which rest on top of the kidneys. ACTH stimulates the adrenal glands to produce cortisol, which is often referred to as “the stress hormone.”³ The cellular receptors that are activated by cortisol are found all over your body, so cortisol affects almost every system. Cortisol works to break down, or catabolize, tissues to provide energy to the body. Cortisol also can also impact brain structures like the hypothalamus, amygdala (one of our centers of emotion and reaction) and prefrontal cortex (responsible for thinking and planning). The immune system-activating action of the initial fight-or-flight response is tempered by cortisol, which has anti-inflammatory and immuno-suppressant action. Finally, and importantly, in a healthy stress response, cortisol inhibits the release of CRF and ACTH, stopping the HPA axis from constantly running.

Clearly, cortisol and the HPA axis response are important for everyday life. Your body needs to be physiologically and mentally prepared to handle stressful situations. But a major issue with modern life is the continuous activation of the body’s stress response without allowing it the chance to recover. We are constantly stressed are rarely get any downtime.

Because of this, the sympathetic and HPA stress responses can go haywire: activating too easily or losing the effect of negative inhibition, in the case of cortisol. When too much cortisol is present too frequently, the receptors for cortisol become less sensitive, meaning there is no inhibition, and cortisol can’t carry out its beneficial actions in the body. Just as the benefits of the stress response and cortisol release are wide ranging, when stress becomes chronic, the negative impacts are equally wide ranging.


These can include muscular atrophy, ulcers, disrupted wound healing, and even be as severe as diabetes and hypertension. Long-term cortisol release or administration has been linked to atrophy of brain regions like the hippocampus, which is a primary site of memory in the brain. Cortisol can also shrink the number of connections in the prefrontal cortex, while augmenting the connections of the amygdala, which upsets the regulatory balance of these brain regions. These brain structure changes are linked with mood dysfunction, which can be as serious as depression and anxiety. Chronic stress has also been tied to inflammatory diseases like rheumatoid arthritis, chronic low back pain, and sciatica.


Given the wide-ranging negative outcomes produced by chronic stress, both psychologically and physiologically, it’s often tricky to pinpoint and treat issues caused by stress. Thankfully, this is where adaptogens can lend a hand.

Adaptogens often function like a biological swiss-army knife, with a diverse range of benefits resulting from their active ingredients.

Adaptogens can be neuroprotective, hepatoprotective [defending your liver], protect against oxidative stress and inflammation, and can even function as anxiolytics. Adaptogens have been shown to elicit stress-protective effects on the endocrine system, the same system that produces the impacts of the HPA axis. A 1985 review of studies involving Eluethero, known as Siberian Ginseng, showed that when given to individuals engaged in high stress occupations (think loud construction sites, air traffic controllers, rescue personnel), Eluethero increased physical and mental work capacities across the board.⁷ ⁸ Further, Rhodiola has been shown to improve symptoms of mental and physical stress, alertness, and even decreased levels of a measure of cortisol.


An adaptogen that exemplifies the wide-ranging benefits of this class of plants and fungi is Ashwagandha. Withania Somnifera is a plant used throughout traditional Ayurvedic medicine. Also known as Indian Ginseng, it is a go-to treatment for dozens of diagnoses for its utility in different systems of the body, and a growing body of research is supporting many age-old claims. The primary identifying and active ingredient in Ashwagandha is a class of molecules known as withanolides. This class is comprised of many different specific molecules, but Withaferin A is likely the most important. Withaferin A and the associated withanolides within Ashwagandha engage cells and systems throughout your body.


Studies on Ashwagandha’s role as an anxiolytic have shown participants having significant improvements on clinical measurements of depression and anxiety, as well as reductions in systemic cortisol measures. Some researchers believe this is a result of Ashwagandha extract’s activity at receptors for the inhibitory neurotransmitter GABA, which has been shown to have an inhibitory role in some mood disorders. Further, Ashwagandha extract decreases the immune system expression of cytokines, which are proteins that start inflammatory processes in your body. This can also impact behavioral and mood diseases that have been linked to increased systemic inflammation.⁹ ¹⁰

RDF's Ashwaganhda comes from a 15:1 root extract to maximize bioactive withanolides.  

At a cellular level, withaferin-A modulates several pro-inflammatory protein and gene pathways. It has even been shown that withaferin-A might show a beneficial preference for inhibiting some pro-inflammatory genes over others, which can improve your body’s ability to balance appropriate levels of inflammation. Far from only acting as an inhibitor, the withanolides in Ashwagandha have shown immune system benefits, increasing natural killer cells and increasing expression of specific cellular immune response factors in times of stress.¹⁰ So, Ashwagandha may help your body avoid over-utilizing the stress response, and it also can help streamline the stress response when it does need to be deployed.

Perhaps most important to remember, though, is that adaptogens should just be a part of your routine. They can be very helpful, but there is no magic bullet, cure-all plant that will make you fit and healthy in one go.

That said, another tool in your toolkit isn’t a bad thing. The formal research on adaptogens is very new and growing, and our understanding of these compounds is growing with it. Make sure you inform yourself before adding anything to your regimen, and remember that health is multi-dimensional and personal. Take time to understand your body and how the foods you eat and the activities you engage in will impact it, and you’ll be able to make decisions that will work for you.



Works Cited

  1. Dictionary.com. “Adaptogen.” Dictionary.com, 2020, www.dictionary.com/browse/adaptogen?s=t. Accessed 18 Dec. 2020.

  2. Harvard Health Publishing. “Understanding the Stress Response - Harvard Health.” Harvard Health, Harvard Health, 1 May 2018, www.health.harvard.edu/staying-healthy/understanding-the-stress-response. Accessed 15 Dec. 2020.

  3. ‌Alschuler, Lise. “HPA Axis & Stress Response: Hypothalamic Pituitary Adrenal Axis | Integrative Therapeutics.” Integrativepro.com, 2016, www.integrativepro.com/Resources/Integrative-Blog/2016/The-HPA-Axis.

  4. ‌Ramamoorthy, Sivapriya, and John A. Cidlowski. “Corticosteroids.” Rheumatic Disease Clinics of North America, vol. 42, no. 1, Feb. 2016, pp. 15–31, 10.1016/j.rdc.2015.08.002.

  5. ‌McEwen, Bruce S. “Central Effects of Stress Hormones in Health and Disease: Understanding the Protective and Damaging Effects of Stress and Stress Mediators.” European Journal of Pharmacology, vol. 583, no. 2–3, Apr. 2008, pp. 174–185, www.ncbi.nlm.nih.gov/pmc/articles/PMC2474765/, 10.1016/j.ejphar.2007.11.071.

  6. ‌Hannibal, K. E., and M. D. Bishop. “Chronic Stress, Cortisol Dysfunction, and Pain: A Psychoneuroendocrine Rationale for Stress Management in Pain Rehabilitation.” Physical Therapy, vol. 94, no. 12, 17 July 2014, pp. 1816–1825, www.ncbi.nlm.nih.gov/pmc/articles/PMC4263906/, 10.2522/ptj.20130597.

  7. ‌Panossian, Alexander, and Georg Wikman. “Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity.” Pharmaceuticals, vol. 3, no. 1, 19 Jan. 2010, pp. 188–224, www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/, 10.3390/ph3010188.

  8. ‌Farnsworth, N. R., et al. “Siberian Ginseng (Eleutherococcus Senticosus): Current Status as an Adaptogen.” Economic and Medicinal Plant Research / Edited by H. Wagner, Hiroshi Hikino, Norman R. Farnsworth, 1985, agris.fao.org/agris-search/search.do?recordID=US201301464826. Accessed 18 Dec. 2020.

  9. ‌Lopresti, Adrian L, et al. “An Investigation into the Stress-Relieving and Pharmacological Actions of an Ashwagandha (Withania Somnifera) Extract: A Randomized, Double-Blind, Placebo-Controlled Study.” Medicine, vol. 98, no. 37, 2019, p. e17186, www.ncbi.nlm.nih.gov/pubmed/31517876, 10.1097/MD.0000000000017186.

  10. ‌White, Peter T., et al. “Natural Withanolides in the Treatment of Chronic Diseases.” Advances in Experimental Medicine and Biology, 2016, pp. 329–373, 10.1007/978-3-319-41334-1_14. Accessed 18 Dec. 2020.

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