How Adaptogens Are Said to Work: Stress Response, HPA Axis and What Is Proven
The HPA axis and cortisol explained in plain words, the ways adaptogens are proposed to act, what is only lab or animal work, and what human trials have and have not shown.
Content last updated . This page has not been medically reviewed.
Safety first. Natural products can cause side effects and interact with medicines. Read who should be careful, by situation before you use anything on this page.
Information only. This page explains a theory and the evidence around it. It does not say any adaptogen lowers cortisol, balances hormones or treats stress, burnout or any condition. Cortisol and the adrenal glands are part of real medical conditions that a clinician must diagnose. If stress, low mood or anxiety is affecting your life, a clinician can help; in the US you can call or text 988 (Suicide & Crisis Lifeline) at any time.
The stress response in plain words
Cortisol is a hormone made by the adrenal glands, two small glands on top of the kidneys. [2] It is sometimes called the "stress hormone" because it helps the body respond to stress. [2] The pituitary gland in the brain makes another hormone, ACTH, which tells the adrenal glands how much cortisol to make. [3] "HPA axis" is shorthand for that chain: hypothalamus, pituitary, adrenal glands (the hypothalamic–pituitary–adrenal axis). [1]Cortisol is measured in medicine to find specific diseases. A cortisol test measures cortisol in blood, urine or saliva, and levels that are too high or too low may point to a problem with the adrenal or pituitary glands. [3] That is a diagnostic tool for a clinician, not a general stress score.
What the adaptogen theory proposes
Traditional and early-research framing (not proof). The adaptogen idea says certain plants raise "non-specific" resistance to stress. Reviews describe this as acting mainly through the HPA axis, in response to external stress. [4] The same review describes a "secondary" group that does not influence the HPA axis directly but affects immune, nervous and endocrine systems. [4] A 2008 European committee paper said it is difficult to relate the adaptogen definition to concepts in contemporary pharmacology, and described the molecular targets responsible for adaptation as still unknown (citing 1999 work). [5]Network ideas. A 2017 review argued that the mechanisms are impossible to describe rationally with the classical one-drug-one-target model and proposed a network pharmacology approach instead. [6] It also noted that it is very unlikely that any phytochemical's activity is specific to one receptor. [6] This is an author's framework, not a result from a human trial.
A skeptical reading. A 2000 review argued that the classical definition of an adaptogen has much in common with views used to explain the placebo effect. [7] The same reviewers concluded that eleuthero contains pharmacologically active compounds, so this is a call to scrutinize the claim of a special category, not a finding that nothing happens. [7]
What laboratory and animal work suggests
Everything in this section is preclinical (cells or animals). It does not tell us what happens in a person taking a supplement.- A 2026 review lists proposed mechanisms for seven plants, including ginsenosides from Panax ginseng suppressing a protein called FKBP51 and withanolides from Withania somnifera inhibiting an enzyme called PDE4D. [1]
- A 2010 review of Rhodiola rosea listed possible mechanisms including interactions with the HPA system (described as cortisol-reducing). [8]
- The same 2026 review cautions that many preclinical studies rely on acute stress models in animals, which may not reflect the chronic stress people experience. [1]
- A 2022 review that searched for in vitro, animal and clinical studies had a focus on animal studies. [9]
- Reviews call the mechanisms complex and not fully understood. [10]
An antioxidant explanation is also debated. The EMA paper noted that strongly antioxidant substances like tocopherols do not exhibit adaptogenic properties, so antioxidant effects cannot be the main action. [5]
What human trials show about cortisol
| Question | What the source found | Evidence label |
|---|---|---|
| Do ashwagandha trials show lower cortisol? | A 2026 meta-analysis of 23 randomized trials (1,706 people) found ashwagandha reduced cortisol compared with placebo, but noted heterogeneity and limited data on some endpoints. [11] | Mixed to promising; heterogeneous; biomarker only |
| Does it change thyroid hormones? | The same review found no effect on TSH or T3 and a modest rise in T4. [11] | Biomarker finding, unclear importance |
| Do other adaptogens have solid cortisol data? | Proper evidence not found in the sources we read for a pooled analysis of cortisol for rhodiola, ginseng, eleuthero or schisandra; we searched PubMed for systematic reviews of adaptogens and cortisol. | Insufficient evidence |
| Do these changes translate into feeling better? | A 2026 review notes only a limited number of studies measure molecular biomarkers such as cortisol dynamics together with clinical outcomes. [1] | Insufficient evidence |
Read this as: some ashwagandha trials report lower cortisol on average, but the pooled results vary, the studies are short, and it is not established that lowering cortisol is why anyone feels differently. These are results for ashwagandha preparations in the trials pooled. They do not transfer to other plants or to your product. See ashwagandha for stress and anxiety for the symptom trials, and genes and biomarkers: what they can and cannot show.
"Adrenal fatigue" and "adrenal support"
These phrases are marketing terms, not diagnoses. The Endocrine Society states that no scientific proof exists to support adrenal fatigue as a true medical condition and that there is no test that can detect it. [12] It also warns that tests offered for it are not based on scientific facts or good studies, and that taking adrenal hormone supplements when you do not need them may cause your own adrenal glands to stop working. [12] That warning is about adrenal hormone supplements; if an adaptogen product uses "adrenal" wording, check what its label actually claims. More in adrenal fatigue claims.Frequently asked questions
What is the HPA axis?
It is the hormone chain linking the hypothalamus and pituitary in the brain to the adrenal glands. The pituitary hormone ACTH tells the adrenal glands how much cortisol to make. [3]
Do adaptogens lower cortisol?
Some ashwagandha trials report lower cortisol on average, but results vary and are measured by lab markers rather than symptoms. [11][1] The research does not show that other adaptogens do, or that lowering cortisol is the reason for any benefit.
Is cortisol a good measure of stress?
Not on its own. Cortisol tests are used to help find conditions where levels are too high or too low, such as problems with the adrenal or pituitary glands. [3] Trials that measure cortisol rarely also measure how people feel. [1]
Are there tests for adrenal fatigue?
The Endocrine Society says there is no test that can detect adrenal fatigue, and that no scientific proof exists to support it as a true medical condition. [12]
Where can I read what the studies found for symptoms?
See research and evidence for the overview and human clinical studies for limits and conflicts of interest.
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
Limits and uncertainty
- Mechanisms are hypotheses; human proof that they explain symptom changes is limited. [1]
- Extract composition and standardization differ across trials, so one result does not apply to another product. [1]
- Cortisol varies through the day and with sleep and illness; the sources we read did not give a single cutoff that means "stressed", so we do not give one.
Safety and who to ask
References
- Nutrients 2026. System-Level, Molecular and Cellular Mechanisms of Selected Plant Adaptogens - A Review. Review, full text read 2026-10-23.
- National Institute of Diabetes and Digestive and Kidney Diseases (NIH). Cushing's Syndrome. Read 2026-10-23.
- MedlinePlus (National Library of Medicine). Cortisol Test. Read 2026-10-23.
- Chin Med 2018. A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide. Review article. Read 2026-10-23.
- European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). Reflection paper on the adaptogenic concept (EMEA/HMPC/102655/2007), adopted 8 May 2008. Read 2026-10-23.
- Ann N Y Acad Sci 2017. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Review, abstract read 2026-10-23.
- J Ethnopharmacol 2000. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look. Review, abstract read 2026-10-23.
- Phytomedicine 2010. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Review, abstract read 2026-10-23.
- Phytomedicine 2022. A literature review of the studies concerning selected plant-derived adaptogens and their general function in body with a focus on animal studies. Abstract read 2026-10-23.
- Nutrients 2021. Plant Adaptogens - History and Future Perspectives. Review, full text read 2026-10-23.
- Planta Med 2026. Hormonal Modulation with Withania somnifera: Systematic Review and Meta-Analysis of Randomized-controlled Trials. Abstract read 2026-10-23.
- Endocrine Society. Adrenal Fatigue. Patient resource, January 25, 2022. Read 2026-10-23.
- National Center for Complementary and Integrative Health (NIH). Ashwagandha: Usefulness and Safety. Read 2026-10-23.