Adaptogens have a marketing problem. The word has been so thoroughly colonised by wellness branding that a supplement with a substantial peer-reviewed evidence base gets lumped in with whatever extract somebody has discovered will photograph well on Instagram. Ashwagandha deserves better than that. The clinical evidence — particularly for KSM-66 and Sensoril, the two patented root extracts with the most robust trial data — is genuinely strong, and the mechanism is specific enough to be clinically useful rather than vaguely wellness-adjacent.
The starting point is not stress. The starting point is the HPA axis and what chronic HPA activation does to the hormonal and metabolic picture over time.
What chronic HPA dysregulation actually produces
The hypothalamic-pituitary-adrenal axis is the body's primary stress response system. Under chronic activation — which in clinical practice means sustained life stress, physical overtraining, sleep insufficiency, inflammatory load, or blood sugar instability — it produces a predictable downstream pattern. Cortisol rises. DHEA-S falls. The ratio between them shifts toward catabolism — the body breaking down faster than it rebuilds. Testosterone, progesterone, and thyroid T3 conversion are all suppressed downstream of this shift. The DUTCH hormone panel makes this pattern visible across the diurnal curve.
The evidence — what the trials actually show
KSM-66 versus Sensoril — the form matters
Both are patented ashwagandha root extracts with published clinical trials. They are not interchangeable and the difference is worth understanding.
| Characteristic | KSM-66 | Sensoril |
|---|---|---|
| Part of plant | Root only | Root and leaf |
| Withanolide content | ≥5% | ≥10% (more concentrated) |
| Typical dose | 300–600mg daily | 125–250mg daily |
| Primary evidence base | Cortisol, testosterone, thyroid, fertility, athletic performance | Cortisol, anxiety, sleep, cognitive function |
| Best clinical fit | HPA recovery with testosterone/thyroid support priority | Anxiety, sleep, cognitive stress response priority |
| Timing | Morning, with food | Can split morning/evening or evening alone for sleep |
The trials behind these doses ran for weeks to a few months. There is little safety information for longer use, which is one more reason to use it for a defined period, not indefinitely.
Unpatented ashwagandha supplements vary significantly in withanolide content and bioavailability. The trials that produced the evidence base used KSM-66 or Sensoril. Using an unspecified "ashwagandha root extract" at unclear withanolide content and expecting trial-equivalent results is optimistic at best.
Where testing fits
There is no test that tells you ashwagandha will work for you. In practice, I consider it when a DUTCH shows high or erratic cortisol alongside a history of chronic stress, overtraining or poor sleep, and I use it for a set period, then review. That is a practice judgement, not something the trials tested. It is not a replacement for dealing with whatever is driving the stress in the first place.
"The trials show ashwagandha can lower cortisol and stress scores for some people over a few weeks. They don't show it rebalances your hormones, and a test can't tell you in advance whether it will work for you."
Cautions and contraindications
Liver injury — the caution that matters most, and one this page left out when first published. Case series from the US Drug-Induced Liver Injury Network and Iceland describe jaundice and liver injury starting 2 to 12 weeks after people began taking ashwagandha; most recovered after stopping (Björnsson et al., Liver International 2020, doi:10.1111/liv.14393). A series from India reported eight cases linked to single-ingredient products, including three deaths in people who already had liver disease (Philips et al., Hepatology Communications 2023, doi:10.1097/HC9.0000000000000270). These are case reports: they show the harm happens, not how often it happens. Stop taking it and see your GP if you notice yellowing of the skin or eyes, dark urine, itching or pale stools. Don't take it if you have liver disease.
Regulators disagree about it. Denmark has made it illegal to sell products containing ashwagandha, based on a risk assessment by the Technical University of Denmark (DTU) that raised concerns about effects on sex hormones and reproduction, and possible effects on metabolism, the immune system and the nervous system (Danish Veterinary and Food Administration, checked 29 September 2026). It remains on sale in the UK.
Ashwagandha is a Solanaceae (nightshade) family plant. Individuals with nightshade sensitivity should approach cautiously. Ashwagandha can raise thyroid hormone levels. That is why it is studied in underactive thyroid, and why it needs caution in an overactive thyroid or Graves' disease. If you take levothyroxine or other thyroid medication, tell your GP before starting and have your levels rechecked. Pregnancy: avoid. Autoimmune conditions where immune stimulation could be problematic — monitor carefully. Sedative medications: potential additive effect on sleep.
Is your HPA axis driving your symptoms?
The DUTCH Plus hormone panel maps your full cortisol diurnal curve, DHEA-S, and downstream sex hormones — confirming whether the HPA dysregulation pattern is present before any protocol is designed around it.
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