Investigation No. 005
Ashwagandha and the Cortisol Story
How one hormone became a marketing category
Cortisol has been turned into a personality. Cortisol face, cortisol belly, cortisol detox — a single lab value carrying an entire industry on its back. Underneath the noise there are real randomised trials of ashwagandha, and they are more interesting than either side of this argument admits. They are also sixty days long, and they moved more than one hormone.
The investigation
- The claim
- “Ashwagandha lowers your cortisol, so it fixes your stress, your sleep, your weight and your burnout.”
- The evidence
The trials are real. In a double-blind, placebo-controlled study, 64 adults with chronic stress took 300 mg of a full-spectrum root extract twice daily for 60 days and showed significant reductions on every stress-assessment scale used, alongside a substantial fall in serum cortisol.
A second randomised, double-blind, placebo-controlled trial in 60 stressed adults found reduced anxiety scores and a greater fall in morning cortisol than placebo. It also found a significant drop in DHEA-S. Ashwagandha is not turning one dial. It is acting on the hypothalamic-pituitary-adrenal axis, and axes have more than one output.
A meta-analysis of five randomised trials in 400 participants found a small but statistically significant benefit for sleep, more pronounced at 600 mg a day or more and at eight weeks or longer. Its authors added that data on serious adverse effects are limited and that more safety data would be needed to judge whether it is safe for long-term use.
Read that last sentence again, because it is the whole episode. The longest trials here run about two months. The product is sold as something you take indefinitely.
And there is a signal in the safety literature. The US Drug-Induced Liver Injury Network's review of herbal and dietary supplement injury names ashwagandha among the major implicated agents — alongside green tea extract, garcinia, kratom and turmeric. Supplement-induced liver injury now accounts for about 20% of the drug-induced liver injury cases in that network.
Ashwagandha is endocrinologically active, and the direction depends on who takes it. In a 60-day placebo-controlled trial testosterone rose in men (p=0.038) and did not move in women (p=0.989); the same trial found cortisol AND DHEA-S both fell. A 2023 trial found free testosterone and luteinising hormone rose in men — while its own primary outcome, perceived stress, was no better than placebo (p=0.867). In perimenopausal women an 8-week trial found the opposite endocrine picture: oestradiol up, FSH and LH down, testosterone unchanged.
It causes liver injury. A case series from Iceland and the US drug-induced liver injury network described cholestatic or mixed injury with jaundice and prolonged itching, 2–12 weeks after starting. A larger Indian series of single-ingredient cases found the same pattern — and among those with pre-existing liver disease, three developed acute-on-chronic liver failure and all three died. Chemical analysis found no adulterant: it was the herb. Herbal and dietary supplements now account for about 20% of drug-induced liver injury cases in the US network, with ashwagandha and turmeric both named.
- The verdict
- Real effects — which is exactly why it has real risksThis is not one of the ones I can wave away, and I am not going to. Multiple randomised, placebo-controlled trials found something on anxiety and on sleep, and that deserves to be said plainly. But a plant with a real effect is a drug with real effects. It moves sex hormones, and not in the same direction in men and women. It lowers DHEA-S alongside cortisol. It causes cholestatic liver injury, and in people who already have liver disease it has caused acute-on-chronic liver failure and death. So: not if you have liver disease, full stop. Caution if you have a hormone-sensitive condition or are on hormonal treatment. For everyone else, treat it as a trial with an end date and a blood test, not a supplement you take forever — and stop immediately for jaundice, dark urine or relentless itching.
- Change our mind
- Trials running twelve months rather than two, with scheduled liver monitoring, and a primary outcome that is something a person experiences rather than something a questionnaire scores.
Show notes
Adaptogen is not a pharmacological class. It is a research category — a mid-twentieth-century Soviet coinage describing a hypothesis, that certain plants raise nonspecific resistance to stress. It was a proposal. It became a shelf.
And cortisol takes its name from cortex: bark. The outer layer. Which is fitting, because that is exactly where this conversation has stayed. We built an industry on one number from the outermost rind of a gland and called it stress.
Here is what actually bothers me about it, as someone who sees the other side of this. Cortisol is not a villain. It is what gets you out of bed. It is what you make more of when you are fighting an infection, healing a wound, or grieving. Chasing it downward as though lower is always better is not a health strategy — it is a misunderstanding of what the hormone is for.
The trials here are genuinely decent, and I want that on the record. Sixty days, a few hundred people, a questionnaire and a morning cortisol. That is a beginning. It is not a permission slip.
Two things that belong in the body of this, not in a footnote. Ashwagandha is usually told as a cortisol story with tolerability mentioned at the end. That order is wrong.
It is not the same drug in men and women. The trials that measured sex hormones found testosterone rising in men and flat in women, and in perimenopausal women found an oestrogenic picture instead — oestradiol up, FSH and LH down. FSH and LH are the pituitary signals that drive the ovary; pushing them down is a real endocrine action, not a wellness effect. That should give pause to any woman with a hormone-sensitive condition — a history of breast cancer, endometriosis, fibroids — and to anyone on hormonal treatment, in either direction. The same trial that lowered cortisol also lowered DHEA-S, which is an androgen precursor, so 'lowers your stress hormone' is not the whole sentence either.
It can injure the liver, and in the wrong patient it has killed. The pattern is cholestatic — jaundice and weeks of itching — starting two to twelve weeks in. In most people it resolved in one to five months. In people who already had chronic liver disease it did not: three of three died. If you have any liver disease, this herb is not for you, and that is not a hedge. For everyone else: know that dark urine, pale stool, yellow eyes or relentless itching means stop and get liver enzymes, today.
This is the general lesson and it is worth saying once plainly, because it applies to almost everything on this map. A plant with a real effect is a drug with real effects. The evidence that ashwagandha does something to anxiety and sleep is the same evidence that says it does something to your hypothalamic-pituitary axis and your bile ducts. You cannot accept one and wave away the other.
Sources
Every paper referenced on air, in the order it comes up. Links go to the publisher via DOI.
- 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 J Psychol Med · 2012 · 34(3):255–262
- Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.Medicine (Baltimore) · 2019 · 98(37):e17186
- Cheah KL, Norhayati MN, Husniati Yaacob L, Abdul Rahman R. Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis.PLoS One · 2021 · 16(9):e0257843
- Halegoua-DeMarzio D, Navarro V. Challenges in herbal-induced liver injury identification and prevention.Liver Int · 2025 · 45(3):e16071
- Björnsson HK, Björnsson ES, Avula B, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network.Liver Int · 2020 · 40(4):825–829
- Philips CA, Valsan A, Theruvath AH, et al. Ashwagandha-induced liver injury — A case series from India and literature review.Hepatol Commun · 2023 · 7(10):e0270
- Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha extract: A randomized, double-blind, placebo-controlled study.Medicine (Baltimore) · 2019 · 98(37):e17186
- Smith SJ, Lopresti AL, Fairchild TJ. Exploring the efficacy and safety of a novel standardized ashwagandha root extract in adults experiencing high stress and fatigue: a randomized, double-blind, placebo-controlled trial.J Psychopharmacol · 2023 · 37(11):1091–1104
- Gopal S, Ajgaonkar A, Kanchi P, et al. Effect of an ashwagandha root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study.J Obstet Gynaecol Res · 2021 · 47(12):4414–4425
This is education, not medical advice. Nothing in this episode is written with knowledge of your history, your medications or your risks. Do not start or stop any treatment on the basis of it — talk to your own physician. Read the full medical disclaimer.