Does ashwagandha help with “adrenal fatigue” and burnout?

Ashwagandha may ease the subjective sense of stress, especially in people under heavy strain. That does not show the plant also treats burnout or restores a supposedly exhausted adrenal gland. Even so, it is widely used for stress, exhaustion and so-called adrenal fatigue. To judge a possible benefit, it helps to look at who took part in the studies, which interactions are possible, and what lies behind the exhaustion.

What ashwagandha actually does in the body

Ashwagandha (Withania somnifera) is considered an herbal adaptogen, the term for substances said to help the body cope with various kinds of strain. Its active compounds include withanolides, a group of steroidal lactones found in the root, among other parts of the plant. They act on several signaling pathways, including the hypothalamic-pituitary-adrenal axis, GABA receptors and inflammatory signaling cascades.

The hypothalamic-pituitary-adrenal axis, or HPA axis for short, controls a large part of the body’s stress response. Under strain, the hypothalamus releases corticotropin-releasing hormone. This signals the pituitary gland to release adrenocorticotropic hormone, ACTH. ACTH in turn prompts the adrenal cortex to produce cortisol. Cortisol makes energy available, dampens inflammation and supports the response to the strain.

When regulation works well, cortisol rises when needed and falls again once the strain eases. Chronic stress can throw this feedback loop off balance. Possible results include persistently high cortisol or a flattened cortisol curve. Fatigue, poor sleep, trouble concentrating and disturbed immune function can come along with it.

Ashwagandha appears to act on cortisol release and may strengthen negative feedback in the hypothalamus and pituitary. In other words, cortisol that is already present signals the brain to throttle further production. Ashwagandha is also credited with GABAergic activity: it may enhance the calming effect of GABA, the brain’s main inhibitory messenger. These possible effects on the HPA axis and the GABA system offer a mechanistic explanation for its use in stress-related complaints.

The term “adrenal fatigue” (in German, “Nebennierenschwäche”) implies that the adrenal glands are worn out and can no longer make enough cortisol. Endocrinology does not support this concept. True adrenal insufficiency, by contrast, is a serious disease with a demonstrably inadequate cortisol supply. It requires hormone replacement therapy. Addison’s disease is one form of primary adrenal insufficiency.

As another explanation for the complaints often called “adrenal fatigue,” HPA axis dysregulation is put forward. This means disrupted signaling between the brain and the adrenal glands while the glands themselves still work. Such a disorder cannot be diagnosed from symptoms alone, however.

What clinical trials on ashwagandha and stress actually show

A frequently cited study is the 2019 randomized controlled trial by Lopresti and colleagues, published in Medicine. According to its description, which has not yet been checked here, adults with chronic stress took 600 mg of ashwagandha root extract daily for eight weeks. Serum cortisol reportedly fell by about 28% compared with placebo. Participants also reportedly scored markedly lower on validated questionnaires such as the Perceived Stress Scale and the Hamilton Anxiety Rating Scale. These standardized instruments measure perceived stress and anxiety symptoms, respectively.

A dose-dependent effect is also described: higher doses reportedly reduced stress and anxiety more. It remains unclear, however, how participants were selected. Alongside the description of them as adults with chronic stress, there is a statement that they were not specifically selected for high stress. This matters for interpretation, because the cortisol-lowering effect seems to be more pronounced when baseline stress or cortisol is elevated.

A 2021 systematic review with meta-analysis in the Journal of Ethnopharmacology is said to have analyzed twelve randomized controlled trials. According to the reported summary, ashwagandha lowered cortisol levels statistically significantly compared with placebo and improved stress and anxiety scores. The effect on cortisol was not consistent across all studies, though: in some, perceived stress improved without any significant change in cortisol.

The evidence is strongest for a reduction in perceived stress in people who are already under heavy strain. The reported drop in cortisol is moderate and seems not to occur when baseline levels are normal. No firm rule for individuals can be derived from this. Nor can the results simply be applied to “adrenal fatigue.” The studies did not examine adrenal function directly; neither adrenal insufficiency nor HPA axis dysfunction had been diagnosed in participants using objective criteria.

How ashwagandha affects the HPA axis and cortisol regulation

According to preclinical studies, withanolides influence the activity of genes involved in the stress response. They may also make glucocorticoid receptors more sensitive. These are the receptors cortisol binds to in order to act. A 2024 literature review is cited as evidence.

If receptors in the hypothalamus and pituitary became more sensitive to circulating cortisol, negative feedback could strengthen: further cortisol production would be braked as soon as enough cortisol is present. Preclinical results describe a possible mechanism here. That does not yet establish a corresponding effect in humans.

Another possible point of action is ashwagandha’s GABAergic activity. GABA lowers the excitability of nerve cells and so has a calming effect on the nervous system. If ashwagandha enhances this inhibition, it could reduce both the sense of stress and the activation of the HPA axis under strain. The effect of benzodiazepines is used as a comparison, with ashwagandha credited with a much weaker effect.

There are also signs of anti-inflammatory properties that could indirectly support HPA axis function. Chronic inflammation can impair signaling through glucocorticoid receptors and so throw the axis off balance. It can also increase the production of pro-inflammatory cytokines. These immune system messengers stimulate cortisol release. Less inflammation could therefore, in theory, help the HPA axis return to normal regulation.

For longer-term use, however, case reports of possible HPA axis suppression are also cited. In one case described in 2021 in the Journal of Clinical Endocrinology, a patient reportedly developed biochemically detectable adrenal insufficiency after several months of taking ashwagandha, which resolved after stopping it. “Biochemically” means that corresponding abnormalities were found in lab values. Another case report from 2022 reportedly described reduced adrenal function after ten weeks of use. It was said to have reversed after a two-week break.

If these reports are confirmed, they could indicate that the cortisol-lowering effect is excessive in some people and suppresses the HPA axis. How often such an effect occurs cannot be determined from case reports.

GABA receptor modulation and anti-anxiety effects

The possible GABAergic activity could explain why ashwagandha is credited with anxiolytic, that is, anti-anxiety, effects. Increased GABA activity lowers the excitability of nerve cells and can have a calming effect. Benzodiazepines and alcohol also act on the GABA system. Ashwagandha is described as having a much weaker effect with a lower risk of dependence or sedation; this comparison, however, is not adequately supported. Sedation refers to a dampening of alertness and attention, which can show up as drowsiness, for example.

Glucocorticoid receptor sensitivity and negative feedback

More sensitive glucocorticoid receptors would respond more strongly to the cortisol already in circulation. If ashwagandha increases this sensitivity, it could thereby strengthen negative feedback. The signal to inhibit further cortisol production would then be clearer once enough is present.

Dose, supplement form and timing: what the evidence supports

Most clinical trials tested standardized extracts, not raw ashwagandha powder. Among the most studied extracts are KSM-66 and Sensoril. KSM-66 is described as a full-spectrum root extract made with a water-based process and standardized to at least 5% withanolides. Sensoril is a root and leaf extract that, according to available information, contains 10% withanolides and 32% oligosaccharides and is made with a different process. Oligosaccharides are short-chain carbohydrates.

Both extracts have been used in clinical trials with positive results. They are not simply interchangeable, though. Both the withanolide composition and its bioavailability differ, meaning the share that becomes available in the body. According to the studies described, KSM-66 has been studied more in connection with stress and cortisol, Sensoril more for anxiety and cognitive function. When comparing products, the extract used and its withanolide content therefore matter.

The most frequently studied dose range is given as 300–600 mg of standardized extract per day. The 2019 study mentioned above, with its marked cortisol reduction, reportedly used 600 mg once daily. There are described signs of a dose-dependent effect, in which higher doses reduced stress and cortisol more. The safety of more than 600 mg daily, however, has not been studied comprehensively. According to available information, there is no formally established tolerable upper intake level. Higher doses have been linked to more frequent gastrointestinal complaints.

Ashwagandha can in principle be taken at different times of day. Some people find it mildly sleep-inducing and therefore prefer the evening. Splitting the dose between morning and evening could, in theory, give a more even effect against stress through the day. If better sleep is the goal, taking the whole dose in the evening could be preferable. Convincing evidence that timing substantially changes effectiveness is lacking, however. Tolerability and personal preference therefore play an important role.

Some studies combined ashwagandha with other adaptogens or nutrients. In one described study from 2020, it was used together with rhodiola (also called roseroot) and B vitamins. Stress and fatigue reportedly improved. Whether this combination worked better than ashwagandha alone remains open: there was no comparison group that received ashwagandha only.

Who is most likely to benefit from ashwagandha, and when caution is needed

Benefits are most likely in people with high baseline stress and elevated cortisol. The studies with marked cortisol reductions reportedly included people with chronic stress whose strain was measured with validated stress scales. When cortisol is already low or normal, a meaningful benefit is considered unlikely; a further drop could be possible in individual cases. No reliable prediction for individuals can be derived from this.

In some studies, ashwagandha raised thyroid hormone levels. This could be of interest in subclinical hypothyroidism, an early-stage underactive thyroid in which free thyroid hormones are still within the reference range. With normal or already increased thyroid function, on the other hand, a further rise can be a problem. A study on subclinical hypothyroidism is cited on this point. Anyone taking levothyroxine or other thyroid medication needs to take possible changes in hormone levels into account; they could make it necessary for a doctor to adjust treatment.

Because of its possible GABAergic effect, ashwagandha can also interact with sedating substances such as benzodiazepines, barbiturates and alcohol. Combining them could increase drowsiness and impair mental performance. Interactions with immunosuppressants are also conceivable. Ashwagandha’s immunomodulating properties could, in theory, counteract a treatment designed to suppress the immune system.

Ashwagandha is not recommended during pregnancy and breastfeeding because of insufficient safety data. It is also advised against in autoimmune diseases because of possible stimulation of the immune system, although the evidence on this is mixed. Caution is needed with a history of stomach ulcers, since ashwagandha may irritate the gastrointestinal lining in some people.

The case reports of suppressed adrenal function described above also raise questions about longer-term use, especially at higher doses. Regular breaks from taking it or cortisol checks are suggested as possible precautions. There is no evidence, however, that they reliably prevent or detect HPA axis suppression.

Examining the stress response: what biomarkers say about HPA function

Whether lab tests make sense before taking ashwagandha for stress or burnout depends on the symptoms and the clinical question. Where appropriate, cortisol and other lab values can serve as a baseline. Serum cortisol is commonly measured but fluctuates widely. Among other things, the value depends on the time of day and recent stress. A single morning cortisol value can point to pronounced abnormalities, but it does not fully reflect how the whole HPA axis is working.

Depending on the question, other markers of inflammation and metabolic health can help with interpretation alongside cortisol:

High-sensitivity C-reactive protein, or hs-CRP, is a marker of systemic inflammation, which can affect HPA axis regulation.
Thyroid-stimulating hormone, or TSH, T4, or thyroxine, and free T3, or triiodothyronine, can help assess whether thyroid function contributes to fatigue or reduced stamina.
Fasting glucose and insulin can point to disturbances in glucose metabolism that affect energy supply and stamina.

Measuring cortisol again after 8–12 weeks can show whether the measured value changed while taking the supplement. On its own, it proves neither that ashwagandha works nor that taking it caused the change. The full picture also includes perceived stress, sleep quality and energy levels. These can improve even when cortisol does not change significantly.

When a problem with HPA regulation is suspected, more advanced tests also come up in the discussion. A four-point salivary cortisol day profile measures cortisol in the morning, at midday, in the evening and at night. It maps the daily, or diurnal, pattern. It can reveal, for example, a blunted morning rise, high evening values or an overall flatter daily curve. Such patterns have been linked to chronic stress and burnout; a 2017 meta-analysis on diurnal cortisol slopes and health outcomes is cited as evidence. Salivary cortisol tests are not uniformly standardized, however, and they can be hard to interpret. On their own, they diagnose neither burnout nor a nonspecific HPA axis dysregulation.

The ACTH stimulation test is described as the gold standard for diagnosing adrenal insufficiency. It checks how the adrenal glands respond to targeted hormonal stimulation. The test is not routinely used for a vaguely defined HPA axis dysregulation, because this concept of complaints is not clearly defined in clinical practice. With marked fatigue, low blood pressure, weight loss and a very low morning cortisol value, it can be useful as part of a medical workup to look for adrenal insufficiency such as Addison’s disease.

Getting a realistic picture of the body’s stress response

Ashwagandha is one of the more promising supplements for reducing stress. Whether taking it makes sense in a given case, though, cannot be decided from the feeling of exhaustion alone. Cortisol regulation, inflammation and metabolism can all contribute to the overall picture. People who take it often do not know whether their cortisol is high, low or in the normal range.

When lab tests are medically indicated, baseline values and a repeat test after 8–12 weeks can document changes and support further assessment. Whether a measure actually helps or a different approach is needed also depends on how the symptoms develop and how they are assessed medically.

Frequently asked questions

What distinguishes “adrenal fatigue” from HPA axis dysregulation?

“Adrenal fatigue” assumes that the adrenal glands are worn out and can no longer produce enough cortisol. Endocrinology does not support this concept. True adrenal insufficiency, by contrast, is a diagnosable disease with an inadequate cortisol supply that requires hormone replacement therapy. Addison’s disease is one form of it.

HPA axis dysregulation describes altered control between the brain and the adrenal glands. Cortisol levels could be elevated, respond more weakly to strain or lose their usual daily rhythm, without the glands themselves failing. Fatigue or stress complaints alone, however, are not enough to establish such a disorder.

Does ashwagandha help if cortisol is already low in burnout?

A meaningful benefit in this situation has not been shown and is considered unlikely when cortisol is already low or the cortisol curve is flattened. At the same time, there is concern that ashwagandha could suppress the HPA axis further. Case reports are cited in which biochemically detectable adrenal insufficiency reportedly developed after longer-term use of moderate doses and receded after stopping. The specific literature references are missing, however.

When there is a relevant medical question, a morning cortisol measurement can point to abnormal values. On its own, it cannot predict whether ashwagandha will help or might make fatigue worse. Burnout also does not automatically mean that cortisol is low.

Which ashwagandha dose is most effective for chronic stress and burnout?

No single most effective dose can be identified, least of all for treating burnout. Studies on stress and cortisol have often used 300–600 mg of standardized root extract daily. For a 2019 randomized controlled trial, 600 mg once daily for eight weeks is reported to have lowered cortisol by about 28%.

There are signs of dose-dependent effects. For more than 600 mg daily, however, there are fewer safety data, and higher amounts have been linked to more gastrointestinal complaints. When comparing products, the milligram figure alone is not enough either: it can only be meaningfully interpreted together with the type and standardization of the extract.

How can you tell whether fatigue comes from disturbed cortisol regulation or something else?

Symptoms alone cannot reliably tell them apart. Altered cortisol regulation can come with poor sleep, trouble concentrating and stronger reactions to stress. Very similar complaints can also occur with thyroid disorders, iron deficiency, low vitamin D, impaired blood sugar regulation or chronic inflammation.

Depending on the question, cortisol, TSH, free T3, free T4, fasting glucose, insulin, hs-CRP and a comprehensive metabolic panel can help with the workup. Such values do not automatically show which bodily mechanism is causing the fatigue or whether ashwagandha would specifically affect it. Which tests make sense depends on the symptoms and the doctor’s findings.

Can long-term use of ashwagandha suppress adrenal function?

Such an effect is described as possible in individual people. Cited case reports involve biochemically detectable adrenal insufficiency with low cortisol levels after several months of use; the symptoms reportedly resolved after stopping. On this account, the cortisol-lowering effect could go beyond normalization in sensitive people and suppress the HPA axis.

The risk is considered possibly greater with longer-term use of high doses. Regular breaks or cortisol checks are suggested as precautions. How often such suppression occurs, and whether these measures protect against it, cannot be determined from the information available.

How does ashwagandha’s GABAergic effect contribute to stress relief?

GABA is the brain’s main inhibitory messenger. Ashwagandha may enhance GABA-mediated inhibition, making nerve cells less excitable and damping the sense of stress. The comparison with benzodiazepines rests on this possible influence on the GABA system; ashwagandha’s effect is described as much weaker. A blanket exclusion of dependence risk has not been established.

The hypothesis is that a smaller excitatory response of the brain to strain could also weaken activation of the HPA axis. This could contribute to less perceived stress and, over time, lower cortisol release.

Are breaks from taking it useful for avoiding HPA axis suppression?

Whether such breaks are necessary or prevent suppression has not been settled. Most studies last only 8–12 weeks. Typical break patterns suggested are two weeks on and one week off, or three months on and one month off. Solid evidence for these schedules is lacking, however.

The theoretical rationale is to prevent reduced receptor sensitivity and give the HPA axis time to recover. Given the case reports described, regular breaks are cited as a possible precaution, especially if the effect wears off after several months or fatigue increases. That this achieves a “reset” of the HPA axis is likewise not solidly established.

Which biomarkers can help you understand the stress response before taking it?

Depending on symptoms, morning serum cortisol, hs-CRP, TSH, free T3 and T4, as well as fasting glucose and insulin, can help with medical assessment. Morning serum cortisol is described as an easily accessible marker of the HPA axis. hs-CRP gives clues about systemic inflammation, which can affect cortisol signaling.

Thyroid values help in working up a dysfunction whose symptoms can resemble those of supposed “adrenal fatigue.” Fasting glucose and insulin provide information about glucose metabolism, which can be affected by persistently high cortisol, among other things.

Together, the values can point to different possible connections: altered stress hormone regulation, thyroid problems, metabolic disorders or inflammation. Each of these calls for a different assessment and, if needed, treatment. The lab values alone, however, determine neither the cause of the symptoms nor a suitable therapy. Routinely measuring all of these markers before every use cannot be justified from the information available.

References and sources

Lopresti AL, Smith SJ, Malvi H, Kodgule R (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine, 98(37), e17186. https://doi.org/10.1097/MD.0000000000017186. PubMed.
Yadav N, Tripathi S, Sangwan NS (2024). Phyto-therapeutic potential of Withania somnifera: Molecular mechanism and health implications. Phytotherapy research : PTR, 38(3), 1695-1714. https://doi.org/10.1002/ptr.8100. PubMed.
Bernasconi AA, Wiest MM, Lavie CJ, Milani RV, Laukkanen JA (2021). Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials. Mayo Clinic proceedings, 96(2), 304-313. https://doi.org/10.1016/j.mayocp.2020.08.034. PubMed.
Sharma AK, Basu I, Singh S (2018). Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. Journal of alternative and complementary medicine (New York, N.Y.), 24(3), 243-248. https://doi.org/10.1089/acm.2017.0183. PubMed.
Adam EK, Quinn ME, Tavernier R, McQuillan MT, Dahlke KA, Gilbert KE (2017). Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis. Psychoneuroendocrinology, 83, 25-41. https://doi.org/10.1016/j.psyneuen.2017.05.018. PubMed.

Further information pages on biomarkers from the original provider; these are not primary scientific evidence: