Ashwagandha, stress and cortisol: what the KSM-66 trials show

KSM-66 is an ashwagandha root extract standardised for withanolides, compounds considered to be the plant’s main active constituents. According to the authors of the original 2012 trial, it is produced without alcohol or synthetic solvents [1]. We have chosen to focus on trials using this extract. ANSES highlights the considerable variation in the composition of ashwagandha preparations depending on which part of the plant is used [2], and a result obtained with one extract does not automatically apply to another.

How should you interpret these trials?

All the trials presented here are randomised, double-blind and placebo-controlled. In other words, participants are randomly assigned to receive either the extract or a capsule with no active ingredient, without them or the investigators knowing who receives which. Stress is measured using the Perceived Stress Scale (PSS), a questionnaire that assesses how overwhelmed people have felt over the past few weeks. Because scores often fall in the placebo group too, what matters is the difference between the two groups. That is why it is useful to compare the final two columns of the table.

As for tolerability, the largest trial to date followed 1,002 adults experiencing stress or anxiety for 8 weeks across several centres. No serious adverse effects were reported. Mild effects, mainly nausea, dry mouth or headaches, were reported by 5.6% of participants taking KSM-66, compared with 9.2% taking placebo. This non-significant difference indicates comparable tolerability [8].

Ashwagandha and anxiety: what the trials measure

Two trials measured anxiety using the Hamilton Anxiety Rating Scale (HAM-A), assessed by a healthcare professional during an interview. In adults experiencing stress, the score fell by 16 % at 600 mg per day, compared with 8 % with placebo, while the lower dose tested in the same trial performed no better than placebo [4]. In adults with insomnia, it fell by nearly 22 %, compared with 8 % with placebo, alongside an improvement in sleep that we discuss in our article on ashwagandha and sleep [5].

It is worth noting that these participants did not have a diagnosed anxiety disorder. An anxiety disorder requires medical care, which a food supplement cannot replace.

What these figures do not tell us

These trials were, however, relatively small, involving between a few dozen and around a hundred participants, and most lasted two months; only one followed its participants for six months. The percentages are also group averages and do not predict how any one person will feel. This is worth bearing in mind when reading the studies.

Average change in scores between the start and end of the trial. Some percentages were calculated from the published averages. For each measure shown, the difference compared with placebo was statistically significant.

Cortisol, a biological marker of stress

Cortisol is a hormone produced by the adrenal glands. It plays a central role in the body's response to stress, as well as in waking, energy regulation and immunity. Its level follows a regular pattern: highest in the morning, it falls throughout the day. Measuring it adds a biological measure to questionnaires, which rely primarily on self-reporting.

Reductions measured in four trials

Four of the trials in the table measured blood cortisol at the start and end of the study. In the KSM-66 groups, it fell by 22 to 36% depending on the trial, compared with 4 to 19% with placebo in the trials that reported this [1][3][4][6]. These results are consistent with the reduction in perceived stress, with two caveats:

• A single measurement does not reflect cortisol secretion over the course of the day.
• Lower cortisol levels are not a goal in themselves. This hormone is essential for the body to function properly.

Who is it for? When should it be avoided?

We designed our ashwagandha capsules for adult women who are not pregnant or breastfeeding: women in perimenopause or menopause, or those who have finished breastfeeding and are carrying a heavy mental load. This decision follows ANSES's April 2024 advice, which recommends against ashwagandha [2]:

• During pregnancy and breastfeeding, and for those under 18;
• If you have a thyroid, liver or heart condition, or hyperandrogenism (as in PMOS, or polyendocrine metabolic ovarian syndrome, formerly known as PCOS);
• If you are taking sedatives or medication that acts on the central nervous system, such as an anxiolytic or a sleeping tablet;
• There is a risk of drowsiness when driving or operating machinery.

If you are taking any medication, speak to your doctor or pharmacist before taking it. All precautions for use are detailed on our page dedicated to ashwagandha.

The KSM-66 course

In the trials presented here, participants took 600 mg of extract per day, in two 300 mg doses, morning and evening, generally after meals [1][7]. Effects were most often assessed after 8 weeks; in one trial, a difference compared with placebo appeared as early as week 4 [3]. It is therefore better to think in terms of a course of around two months, then review how things stand and speak to a healthcare professional if you are considering taking it for longer.

The extract used in our capsules

For our KSM-66 ashwagandha capsules, we chose the root extract studied in these trials, at the dose used in the studies: 600 mg per day, or two capsules. The extract is organically grown, and the capsules are vegan and made in France.

Finally, remember that a supplement never works in isolation: sleep, physical activity, time for yourself and support from those around you remain the first ways to address stress. To discover other products designed for demanding periods, explore our anti-stress collection.