The properties of ashwagandha (Withania somnifera) and, in particular, the documented benefits of the patented ashwagandha KSM-66 extract, have been the subject of the largest body of human clinical research on this adaptogenic plant traditionally used in the Ayurvedic medicine of India for more than 3,000 years. The ashwagandha KSM-66 extract, obtained exclusively from the root and standardized to 5% withanolides (the main bioactive components), concentrates the clinical studies on physiological stress markers (salivary and serum cortisol), sleep quality and performance-related parameters. This page covers what it is used for, how it works, the studied dosages, the differentiated benefits by profile (including use in women), where it fits within the Pleniage portfolio and what precautions to keep in mind.
What is ashwagandha?
Ashwagandha (Withania somnifera, also known as "Indian ginseng" or "winter cherry") is a perennial shrub native to the Indian subcontinent and to some regions of North Africa. The part of the plant used in supplementation is the root, where the withanolides are concentrated, a family of steroidal lactones considered the main bioactive components of the extract.
In the Ayurvedic medicine of India it has been traditionally used for more than 3,000 years in the rasayana category (literally "path of essence"), a group of plants with a historical use oriented toward the overall balance of the body. Modern scientific research on ashwagandha has grown especially over the last two decades, focusing above all on its adaptogenic profile (the ability to modulate the physiological response to stress).
KSM-66 vs generic ashwagandha: what changes
Not all commercial ashwagandhas are equivalent. The differences between extracts can be substantial and determine whether clinical research results can be extrapolated. The KSM-66 extract (Ixoreal Biomed) is the most widely used in published human clinical trials on ashwagandha, and it is distinguished by three features:
- Exclusively root-derived: it uses only the root of the plant, not leaves or stems. The root contains the withanolide profile associated with the studied adaptogenic effects; the leaves have a different profile (with a higher proportion of withaferin A, associated with other biological pathways and greater potential for irritation).
- Standardization to 5% withanolides verified batch by batch. It is the highest percentage among the pure-root extracts available commercially and the one used in most of the relevant clinical trials.
- Aqueous milk-based extraction process following a modernized traditional Ayurvedic method, without organic solvents. This preserves the complete withanolide profile without exogenous components.
The practical consequence is that the results of clinical trials conducted with KSM-66 are not directly extrapolable to other ashwagandha extracts that use different parts of the plant, lower standardizations or different extraction processes. When a product fact sheet or a supplement cites "ashwagandha", it is worth verifying whether it is KSM-66 or a generic extract.
How it works: the HPA axis and cortisol modulation
The hypothalamic-pituitary-adrenal axis (HPA axis) is the hormonal cascade that regulates the body's response to stress. In the presence of a stressful stimulus, the hypothalamus releases CRH (corticotropin-releasing hormone), which stimulates the pituitary to release ACTH (corticotropin), which in turn stimulates the adrenal glands to release cortisol.
Cortisol is an essential hormone: it regulates glucose metabolism, modulates the immune response and maintains blood pressure. The problem arises when the HPA axis is chronically activated (sustained, prolonged stress) and cortisol levels remain persistently elevated, a phenomenon associated with fatigue, difficulty falling asleep, mood alterations and other systemic effects.
The body of clinical research with ashwagandha (KSM-66) has documented decreases in morning salivary cortisol and in serum cortisol in people with chronic stress after supplementation for 60-90 days. The predominant mechanistic interpretation is that of adaptogenic modulation of the HPA axis, without a single exclusive receptor or pathway having been identified.
Clinical evidence: stress, sleep and performance
The largest body of human clinical evidence on ashwagandha corresponds to studies conducted with the KSM-66 extract. The three most researched areas are:
Stress and cortisol
The trial by Lopresti and colleagues published in Medicine (Baltimore) in 2019 studied 60 adults with high self-perceived stress, randomly assigned to receive 600 mg/day of KSM-66 or placebo for 60 days. The KSM-66 group documented a reduction in morning salivary cortisol of approximately 23% relative to baseline, together with decreases in self-administered stress scales.
Earlier, the study by Chandrasekhar and colleagues published in the Indian Journal of Psychological Medicine in 2012 documented consistent results in a sample of 64 people with chronic stress (KSM-66 600 mg/day for 60 days): a decrease in the PSS-10 scale (Perceived Stress Scale) and in serum cortisol.
The meta-analysis by Bonilla and colleagues published in the Journal of Functional Morphology and Kinesiology in 2021 synthesized the available evidence (ashwagandha in general, including KSM-66 and other extracts) on stress and anxiety and concluded that there is a consistent effect of small-to-moderate magnitude, with KSM-66 being one of the extracts with the largest number of trials.
Sleep quality
The trial by Salve and colleagues published in Cureus in 2020 studied 80 people with subjective sleep complaints, assigned to receive 250 mg or 600 mg/day of KSM-66 or placebo for 8 weeks. The KSM-66 group documented improvements in the PSQI scale (Pittsburgh Sleep Quality Index) and a reduction in subjective sleep latency relative to baseline.
Physical performance and testosterone
To complete the profile, the trial by Wankhede and colleagues published in the Journal of the International Society of Sports Nutrition in 2015 studied 57 young men in a strength-training program for 8 weeks, assigned to 600 mg/day of KSM-66 or placebo. The KSM-66 group documented increases in markers of muscle strength, fat-free mass and serum testosterone.
It is important to contextualize this study: the sample is exclusively male, young and actively training. The testosterone results are not extrapolable to women, older men or untrained individuals, although they are often cited outside that context in commercial marketing.
Benefits of ashwagandha for women: context and evidence
One of the most frequent questions about the benefits of ashwagandha for women concerns its effects on stress, sleep quality and general well-being in female profiles. The clinical trials on salivary cortisol (Lopresti 2019) and subjective sleep quality (Salve 2020) included participants of both sexes, and the results on stress and sleep are applicable to both women and healthy adult men.
However, specific areas require honest qualification. The data on testosterone and physical performance (Wankhede 2015) are not extrapolable to women, as they come from an exclusively male sample. In contexts such as menopause, female thyroid function or specific hormonal balance, the clinical evidence with KSM-66 is preliminary and it is advisable to assess each case with a physician, especially if there is ongoing hormonal treatment. Ashwagandha is contraindicated during pregnancy and breastfeeding as a general precaution (see the contraindications section).
Studied dosages and time of day
The dosages investigated in the main clinical trials with KSM-66 range between 250 mg and 600 mg per day, in a single intake or divided into two. The dose of 600 mg/day (often divided into 2 × 300 mg) is the most widely used in trials on stress and performance.
The time of day of the intake is not standardized in the research. Some protocols administer the dose with breakfast and dinner, others in a single morning intake. The usual practical choice:
- A morning and/or evening intake with food improves digestive tolerance.
- For a sleep-focused use, an evening intake (with dinner or 1-2 hours before sleeping) is the most widely used schedule.
- Recommended minimum duration: the effects on stress and sleep markers are typically documented from 4-8 weeks of continued use.
Side effects and precautions (including constipation)
Ashwagandha has a favorable safety profile at the usual dosages in healthy adults. The most frequently reported side effects, although still uncommon, are gastrointestinal:
- Mild digestive discomfort: gastric upset, a feeling of heaviness at the start of treatment. These generally resolve by taking it with food.
- Constipation: it is one of the digestive effects most mentioned by consumers in qualitative reviews and consultations. The probable cause is a combination of the general adaptogenic effect (relaxation of intestinal motility in some people) and the extract matrix itself. It is usually mild and transient; it is managed with good hydration, dietary fiber and taking it with meals. If the constipation is intense or persistent, it is advisable to review the dose or discontinue.
- Mild hypotension in predisposed individuals (it may potentiate the hypotensive effect of antihypertensive medications — see the interactions section).
- Daytime drowsiness: uncommon at the usual dosages, more likely with high doses or a poorly scheduled evening intake.
EFSA has not established a specific tolerable upper level (UL) for ashwagandha as a food supplement. The Italian authority AIFA recommends not exceeding 1,000 mg/day of dried titrated root extract as a general reference for supplements.
Contraindications
- Pregnancy and breastfeeding: contraindicated. Ashwagandha has activity on the uterine muscle documented in animal studies and has traditionally been associated with abortifacient use at high doses. There are insufficient safety data in humans during pregnancy or breastfeeding.
- Hyperthyroidism: ashwagandha may modulate thyroid function (some studies document slight increases in T4 and decreases in TSH). In people with hyperthyroidism or treated with levothyroxine, this modulation may be inadvisable. Prior medical consultation is mandatory.
- Autoimmune diseases (rheumatoid arthritis, lupus, multiple sclerosis, inflammatory bowel disease): ashwagandha has immunomodulatory activity documented in preclinical studies. In autoimmune diseases it is recommended to avoid it or to consult the specialist.
- Scheduled surgery: because of its effect on the central nervous system and the possible interaction with anesthetics, it is recommended to discontinue it at least 2 weeks before surgery.
Drug interactions
- Sedatives (benzodiazepines, hypnotics): a possible additive effect. Risk of excessive drowsiness.
- Antihypertensives: ashwagandha may potentiate the hypotensive effect.
- Oral antidiabetics and insulin: a possible additive effect on blood glucose. Monitoring is recommended.
- Immunosuppressants (tacrolimus, ciclosporin, biologics in autoimmune conditions): the immunomodulatory activity of ashwagandha may interfere.
- Thyroid hormone (levothyroxine): a possible modification of TSH levels. Monitoring if ashwagandha is started in patients under treatment.
In general, before combining ashwagandha with any chronic or acute medication it is advisable to consult the physician or pharmacist.
How to choose an ashwagandha supplement
- Form of the extract: prioritize standardized pure-root extracts (such as KSM-66) over non-standardized extracts or those that combine root and leaves.
- Standardization in withanolides: verify the percentage (KSM-66 is at 5%; other extracts may be between 1.5% and 10% but with a different qualitative profile).
- Dose consistent with the evidence: 250-600 mg/day is the range with the largest number of clinical trials. Very low doses (<100 mg) or very high doses (>1,200 mg/day) fall outside the studied profile.
- Traceability and certificates of analysis: prioritize brands that publish third-party analyses confirming standardization and the absence of contaminants (heavy metals, pesticides).
- Origin: ashwagandha grown under organic farming standards reduces exposure to pesticide residues.
Ashwagandha in the Pleniage portfolio
If you are considering buying ashwagandha backed by clinical evidence, ashwagandha KSM-66 is part of the formulation of PLENIAGE® PRO CALM+ in its KSM-66 BIO form (patented root extract at 5% withanolides, organic certification). PRO CALM+ combines ashwagandha KSM-66 with magnesium bisglycinate Albion TRAACS®, L-theanine (without EGCG), Rhodiola at 3% rosavins and B-group vitamins (B6, B9, B12). Each ingredient has its own individual scientific research; the specific combination of this formula has not been the subject of a dedicated clinical trial.
This page is part of the Calm and balance cluster. To explore other related components in depth, see the fact sheets (coming soon) on Magnesium bisglycinate, L-theanine and Rhodiola.
Frequently asked questions about ashwagandha
Is ashwagandha useful for stress?
The largest body of clinical evidence on ashwagandha (especially with the KSM-66 extract) has documented decreases in morning salivary cortisol and in serum cortisol in people with chronic stress after 60-90 days of supplementation, together with improvements in self-administered scales such as the PSS-10. The predominant interpretation is that of adaptogenic modulation of the HPA axis. It is a complementary route to structural habits (sleep, exercise, psychological stress management), not a substitute for them.
Does ashwagandha cause constipation?
Constipation is one of the digestive effects most mentioned by consumers. The probable cause is a combination of the general adaptogenic effect on intestinal motility and the extract matrix itself. It is usually mild and transient; it is managed with good hydration, dietary fiber and taking ashwagandha with food. If the constipation is intense or persistent, it is advisable to review the dose or discontinue. It is not an effect that affects most consumers, but it is reasonably frequent in consultations.
How long does it take to feel the effect of ashwagandha?
The effects on stress and sleep markers are typically documented in clinical trials from 4-8 weeks of continued use. Some people report subjective changes earlier (better sleep within 2-3 weeks), but an honest evaluation of objective markers requires at least 6-8 weeks of use. If no changes are noticed after 8-12 weeks, it is advisable to review the dose, the schedule or to seek advice to rule out other causes of the original problem.
Can I take ashwagandha during pregnancy?
No. Ashwagandha is contraindicated during pregnancy and breastfeeding. It has activity on the uterine muscle documented in animal studies and has traditionally been associated with abortifacient use at high doses. There are insufficient safety data in humans in these contexts. If you are pregnant, planning a pregnancy or breastfeeding, consult your physician before any supplementation.
Does ashwagandha increase testosterone?
There is one trial (Wankhede 2015) in young men in strength training that documented increases in serum testosterone with KSM-66 at 600 mg/day for 8 weeks. It is important to contextualize: the sample is exclusively male, young and actively training. The results are not extrapolable to women, older men or untrained individuals, although they are often cited outside that context in commercial marketing. Ashwagandha is not a substitute for medical evaluations if the concern is a real hormonal deficit.
Is any ashwagandha on the market the same?
No. The differences between extracts can be substantial and determine whether clinical research results can be extrapolated. KSM-66 uses only the root, is standardized to 5% withanolides and is the extract with the largest number of published human clinical trials. Other extracts may combine root and leaves (a different qualitative profile) or have lower standardizations. When a product cites "ashwagandha", it is worth verifying whether it is KSM-66 or a generic extract before assuming that the same results apply.
Does it have contraindications or interactions?
Yes, several relevant ones. It is contraindicated during pregnancy and breastfeeding, in hyperthyroidism (it may modulate thyroid function), in autoimmune diseases and before scheduled surgery (discontinue at least 2 weeks before). It has potential interactions with sedatives (additive effect), antihypertensives (potentiation), antidiabetics (modification of blood glucose), immunosuppressants (interference) and thyroid hormone (modification of TSH). If you take chronic medication, consult your physician before starting to supplement with ashwagandha.
Ashwagandha (Withania somnifera) is an adaptogenic plant with traditional Ayurvedic use, whose modern clinical evidence profile in humans has consolidated especially with the KSM-66 extract on physiological stress markers (cortisol), sleep quality and, in specific samples, parameters related to physical performance. It is not a substitute for structural habits (sleep, exercise, stress management) or for medical treatments when these are necessary; it is a complementary tool with a favorable safety profile at the studied dosages, provided that the contraindications are respected and the matter is assessed with a physician when there are ongoing chronic treatments.
At PLENIAGE® we publish scientific content on evidence-based supplementation. You can explore the Calm and balance cluster for more fact sheets and related articles.
References
The article's statements are based on available scientific literature. Below are the key verified references that support the main claims about the KSM-66 extract of ashwagandha.
- 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. PMID: 31517876.
- 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. PMID: 23439798.
- Salve J, Pate S, Debnath K, Langade D. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus. 2019;11(12):e6466. PMID: 32021735.
- Wankhede S, Langade D, Joshi K, Sinha SR, Bhattacharyya S. Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. J Int Soc Sports Nutr. 2015;12:43. PMID: 26609282.
- Bonilla DA, Moreno Y, Gho C, Petro JL, Odriozola-Martínez A, Kreider RB. Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis. J Funct Morphol Kinesiol. 2021;6(1):20. PMID: 33670194.