Evidence Level
Moderate
7 Clinical Trials
6 Documented Benefits
3/5 Evidence Score

KSM-66 is the most extensively studied branded ashwagandha (Withania somnifera) extract, made by Ixoreal Biomed. It is a full-spectrum, root-only extract produced with a proprietary water-based process that uses no alcohol or harsh solvents, which preserves the natural balance of the root's compounds while standardizing it to at least 5% withanolides. Ixoreal counts more than 20 human trials on the extract, and KSM-66 is named in the published text of most of the ones cited here. The strongest evidence is for perceived stress and serum cortisol. Sleep, memory, strength, endurance and serum testosterone have each been measured in one or two small randomized trials, nearly all run at single centres in India with the manufacturer involved. Independent meta-analyses that pool these trials find real effects but rate the certainty of the evidence as low. Most studies use 300 mg twice daily.

Studied Dose 600 mg/day of root extract, usually 300 mg twice daily, in most trials; a 250 mg/day arm was also tested, and 675 mg/day in the oligospermia trial.
Active Compound Withanolides (≥5%)

Benefits

Stress and Cortisol Balance

Helps the body adapt to stress and supports healthy cortisol levels. At 300 mg twice daily it has reduced perceived stress scores and lowered elevated cortisol versus placebo in chronically stressed adults.

Anxiety and Mood

In an 8-week trial of 60 stressed but healthy adults, 600 mg a day lowered Perceived Stress Scale scores, serum cortisol and Hamilton Anxiety scores more than placebo. A 250 mg a day arm did less, and its Hamilton Anxiety score did not separate from placebo. An independent meta-analysis pooling 12 ashwagandha trials in 1,002 people found significant reductions in anxiety and stress, but rated the certainty of that evidence as low, with wide variation between trials.

Sleep Quality

In a 10-week randomized trial of 60 people with insomnia and anxiety, 300 mg twice daily shortened sleep onset latency to 29.0 minutes against 33.9 minutes on placebo and improved sleep efficiency and Pittsburgh Sleep Quality Index scores. In healthy stressed adults, sleep quality also improved on a simple rating scale. It is not a sedative and does not work on the first night; changes build over weeks.

Memory and Focus

The one cognitive trial gave 300 mg twice daily for 8 weeks to 50 adults diagnosed with mild cognitive impairment, and found better immediate and general memory, executive function, sustained attention and processing speed than placebo. No KSM-66 trial has tested memory or focus in adults with normal cognition.

Strength, Endurance, and Recovery

In 57 untrained young men doing 8 weeks of resistance training, 300 mg twice daily produced larger gains in bench-press 1-RM (46.0 kg against 26.4 kg on placebo) and leg-extension 1-RM, larger arm and chest measurements, and a smaller rise in creatine kinase after exercise. In 50 healthy athletic adults, VO2 max rose 5.67 mL/kg/min from baseline over 12 weeks against 1.86 on placebo. Both trials were small, single-centre and manufacturer-linked.

Serum Testosterone and Sperm Measures

Serum testosterone was a secondary measure in the resistance-training trial, where it rose 96.2 ng/dL on KSM-66 against 18.0 ng/dL on placebo over 8 weeks in 57 untrained young men. The sperm count and motility findings come from a separate 90-day pilot in 46 men diagnosed with oligospermia, and they do not tell you what the extract does in fertile men. Ashwagandha is not a treatment for infertility or for low testosterone.

Mechanism of action

1

Stress and Anxiety Reduction

Serum cortisol fell in the human trials, which is consistent with damping of the hypothalamic-pituitary-adrenal axis. GABA receptor activity from withanolides is a laboratory finding and has not been measured in people.

2

Cognitive Enhancement

In animal and cell studies, withanolides inhibit acetylcholinesterase and so raise acetylcholine. It also reduces oxidative stress in the brain, protecting neurons and supporting synaptic plasticity.

3

Improved Sleep Quality

GABAergic activity is a laboratory finding for withanolides rather than something measured in the sleep trials, which recorded shorter sleep onset latency and better sleep efficiency by actigraphy. Its stress-reducing effects further support sleep by lowering cortisol-driven arousal.

4

Enhanced Physical Performance

Improved mitochondrial function and oxygen use are proposed from preclinical work; the human trials measured VO2 max, 1-RM strength, muscle size and serum creatine kinase, and no mitochondrial marker. It also reduces exercise-induced muscle damage by lowering oxidative stress and inflammation.

5

Testosterone and Fertility Support

Animal work reports increased activity of steroidogenic enzymes and antioxidant protection of testicular tissue. In people, the trials measured serum testosterone and semen parameters directly; the pathway connecting the two has not been demonstrated in humans.

6

Immune Effects (Laboratory and Animal Work Only)

Changes in natural killer cell activity and cytokine production have been reported in laboratory and animal work with Withania somnifera, not in the KSM-66 trials cited here. No trial on this page measured an immune outcome in people, so this remains a proposed mechanism only.

Clinical trials

1
KSM-66® for Stress Reduction — Chronic Stress Clinical Trial
PubMed

Prospective, randomized, double-blind, placebo-controlled study of KSM-66 ashwagandha root extract (300 mg twice daily, 600 mg/day) vs placebo in 64 chronically stressed adults for 60 days. Outcomes: Perceived Stress Scale (PSS), DASS-21, serum cortisol, safety. (Indian J Psychol Med)

64 chronically stressed adults. 60-day intervention.

Perceived Stress Scale scores fell 44.0% from baseline in the KSM-66 group against 5.5% in placebo, and serum cortisol fell 27.9% from baseline against 7.9% in placebo, with both between-group differences statistically significant. DASS-21 subscales also improved. The 44% and 28% figures are changes from baseline inside the treated group, not the size of the gap over placebo. Generally well-tolerated. Critical context: this is the foundational stress trial heavily cited in ashwagandha marketing. Industry-funded (Ixoreal Biomed). Independent replication has been broadly supportive but with smaller effect sizes.

2
Memory and Cognition in Adults with Mild Cognitive Impairment: Randomized Pilot Trial
PubMed

Randomized, double-blind, placebo-controlled pilot trial of ashwagandha root extract, 300 mg twice daily, vs placebo in 50 adults diagnosed with mild cognitive impairment, for 8 weeks. Outcomes: Wechsler Memory Scale III subtests, Eriksen Flanker task, Wisconsin Card Sort, Trail-Making part A, Mackworth Clock. (J Diet Suppl)

50 adults with diagnosed mild cognitive impairment, not healthy adults with ordinary memory complaints. 8-week intervention.

At 8 weeks the extract group improved more than placebo on immediate and general memory (Wechsler Memory Scale III logical memory, verbal paired associates, faces and family pictures) and on executive function, sustained attention and information-processing speed. The paper reports its outcomes after eight weeks of treatment. Because everyone in the trial had diagnosed mild cognitive impairment, it does not show what the extract does for memory in adults with normal cognition. The trial was manufacturer-linked, and the published report does not name the extract as KSM-66.

3
Sleep: Systematic Review and Meta-Analysis of Ashwagandha Extracts, Not a KSM-66 Trial
PubMed

Systematic review and meta-analysis of five randomized placebo-controlled trials, 400 participants in total, of ashwagandha extracts from several different brands, including KSM-66 and Shoden. Cheah, Norhayati, Husniati Yaacob and Abdul Rahman, PLoS One 2021. This is a pooled analysis of other people's trials, not a study conducted in people.

Not a study population: five randomized trials totalling 400 adults, pooled across several different ashwagandha extracts.

The pooled effect on overall sleep was small but significant: standardized mean difference -0.59 (95% CI -0.75 to -0.42), with substantial variation between trials (I-squared 62%). Effects were larger in adults diagnosed with insomnia, at 600 mg/day or more, and at 8 weeks or longer. Mental alertness on rising and anxiety improved; quality of life did not. A KSM-66-specific sleep trial does exist separately: Langade and colleagues gave 300 mg twice daily for 10 weeks to 60 people with insomnia and anxiety and measured sleep onset latency of 29.0 minutes against 33.9 on placebo, with better sleep efficiency and PSQI scores.

4
KSM-66® for Cardiorespiratory Endurance and Recovery — Clinical Trial
PubMed

Randomized, double-blind, placebo-controlled trial of KSM-66 (600 mg/day) vs placebo in 50 healthy athletic adults over 12 weeks. Outcomes: VO2 max measured on a 20 m shuttle run test, and the WHO self-reported quality-of-life questionnaire. No recovery marker was measured. (Ayu)

50 healthy athletic adults, of whom 24 on KSM-66 and 25 on placebo completed. 12-week intervention.

Mean VO2 max rose 4.91 mL/kg/min from baseline on KSM-66 against 1.42 on placebo at 8 weeks, and 5.67 against 1.86 at 12 weeks. Self-reported quality-of-life scores improved more on KSM-66. The widely quoted 13.6% figure is the within-group rise from baseline, not the advantage over placebo, and no recovery marker was measured. A change of this size from a botanical is large enough to need independent replication, and much ashwagandha performance marketing rests on this one small industry-funded trial.

5
Sperm Count and Testosterone in Men Diagnosed with Oligospermia: Pilot Randomized Trial
PubMed

Randomized, double-blind, placebo-controlled pilot trial of KSM-66 root extract, 675 mg/day in three divided doses, vs placebo in 46 men with oligospermia (21 treated, 25 placebo) for 90 days. Outcomes: sperm count, semen volume, sperm motility, serum testosterone and LH. (Evid Based Complement Alternat Med)

46 men diagnosed with oligospermia (sperm count under 20 million/mL), a clinical infertility population rather than healthy men. 90-day intervention.

From baseline to day 90 the treated group showed a 167% rise in sperm count, a 53% rise in semen volume, a 57% rise in motility and a 17% rise in serum testosterone (4.45 to 5.22 ng/mL); the paper describes the change in the placebo group as minimal. Every one of those percentages is a within-group change from baseline, not the gap over placebo. With 21 men treated, in a population with a diagnosed fertility problem, these numbers do not carry over to fertile men or to general testosterone support.

6
KSM-66® for Sexual Function in Healthy Women — Clinical Trial
PubMed

Randomized, double-blind, placebo-controlled pilot trial of KSM-66 root extract, 300 mg twice daily, vs placebo in 50 healthy women for 8 weeks. Outcomes: Female Sexual Function Index, Female Sexual Distress Scale, and the number of successful sexual encounters. Dongre, Langade and Bhattacharyya, BioMed Research International 2015.

50 healthy women. 8-week intervention.

FSFI total score and the arousal, lubrication, orgasm and satisfaction domains improved more than placebo, as did the sexual distress score and the number of successful sexual encounters. This was a 50-woman pilot at a single Indian centre with manufacturer involvement, and no hormones were measured, so the reason for the effect is unknown.

7
Safety: Animal Toxicology Plus Reported Liver Injury Cases, Not an Efficacy Trial
PubMed

This entry is not a clinical trial. It combines manufacturer-sponsored genotoxicity and animal toxicity testing of KSM-66 with the published human case reports of liver injury from ashwagandha supplements.

Not applicable: laboratory and animal toxicology, plus case reports in people.

Manufacturer-sponsored testing reported no significant effect on blood counts or on liver, kidney and thyroid markers, and the trials on this page reported mild adverse events at rates similar to placebo. Against that, Bjornsson and colleagues described five cases of liver injury attributed to ashwagandha supplements in Liver International in 2020: all five developed jaundice 2 to 12 weeks after starting, the injury pattern was cholestatic or mixed, and liver tests returned to normal within 1 to 5 months. The NIH LiverTox database lists ashwagandha as a cause of drug-induced liver injury. The reaction appears rare and idiosyncratic. Stop taking it and seek medical advice if jaundice, dark urine, itching or persistent nausea develop.

Side effects and drug interactions

Common Potential side effects

Gastrointestinal discomfort: mild stomach upset, nausea, or loose stools can occur, more likely at higher doses or on an empty stomach.
Drowsiness: its calming effect can cause mild sleepiness, especially at higher doses or when combined with sedatives.
Headache: a small number of people report mild headaches, which are often dose-related.
Allergic reactions: rarely, skin rash or itching can occur in people sensitive to ashwagandha, which is a nightshade-family plant.
Lowered blood pressure: may modestly lower blood pressure, which can cause lightheadedness in people who already run low or take blood-pressure medication.
Thyroid and hormonal effects: can raise thyroid hormone levels, so use caution with thyroid conditions or medication; it is not recommended during pregnancy. Liver injury: rare cases of cholestatic or mixed liver injury with jaundice have been reported 2 to 12 weeks after starting ashwagandha supplements, and the NIH LiverTox database lists ashwagandha as a cause of drug-induced liver injury; stop and seek medical advice if jaundice, dark urine, itching or persistent nausea occur.

Important Drug interactions

Sedatives and CNS depressants (benzodiazepines, sleep medications, alcohol): may add to their calming, sedative effect.
Thyroid medication (levothyroxine): ashwagandha can raise thyroid hormone levels and may add to thyroid medication, so monitor thyroid labs.
Immunosuppressants: its immune-stimulating activity may work against drugs meant to suppress the immune system, such as after a transplant or for autoimmune disease.
Blood pressure and diabetes medication: may add to the effects of antihypertensive and blood-sugar-lowering drugs.
Other sedative or thyroid-active supplements: effects may be additive; combine with care.

Frequently asked questions about KSM-66®

What makes KSM-66 different from regular ashwagandha?

KSM-66 is a branded, standardized full-spectrum ashwagandha root extract made by Ixoreal Biomed using a proprietary water-based process that avoids alcohol and harsh solvents. It is standardized to at least 5% withanolides and is the most clinically studied ashwagandha, so when research refers to a specific branded extract it is often KSM-66. Generic ashwagandha can vary widely in potency and quality, whereas a branded, standardized extract is more consistent from batch to batch.

Is KSM-66 better than Sensoril or Shoden?

They are different standardized ashwagandha extracts with different profiles. KSM-66 is a root-only, full-spectrum extract standardized to about 5% withanolides and has the largest body of research, spanning stress, sleep, strength, and testosterone. Sensoril uses root and leaf and is standardized to a higher withanolide level, and Shoden is a high-withanolide extract often studied for sleep. The best choice depends on your goal; KSM-66 is the most broadly studied.

Should I take KSM-66 in the morning or at night?

Either works, and it depends on your goal. For daytime stress and focus, a morning or split dose (such as 300 mg twice daily) is common. For sleep, an evening dose is often preferred. Because it works gradually by retuning the stress response rather than acting as a fast sedative, daily consistency matters more than the exact time.

What is KSM-66?

KSM-66 is the most extensively studied branded ashwagandha (Withania somnifera) extract, made by Ixoreal Biomed. It is a full-spectrum, root-only extract produced with a proprietary water-based process that uses no alcohol or harsh solvents, which preserves the natural balance of the root's compounds while standardizin…

What is KSM-66 used for?

KSM-66 is researched primarily for Cognitive, Athletic Performance, and Sleep Health. Helps the body adapt to stress and supports healthy cortisol levels. At 300 mg twice daily it has reduced perceived stress scores and lowered elevated cortisol versus placebo in chronically stressed adults.

What is the recommended dosage of KSM-66?

The clinically studied dose is 600 mg/day of root extract, usually 300 mg twice daily, in most trials; a 250 mg/day arm was also tested, and 675 mg/day in the oligospermia trial. Always follow the product label and check with a healthcare provider for personal advice.

Is KSM-66 safe, and does it have side effects?

For most healthy adults, KSM-66 is well tolerated at studied doses. Reported effects can include: Gastrointestinal discomfort: mild stomach upset, nausea, or loose stools can occur, more likely at higher doses or on an empty stomach. Drowsiness: its calming effect can cause mild sleepiness, especially at higher doses or when combined with sedatives. It may also interact with some medications. KSM-66 is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does KSM-66 interact with any medications?

Possible interactions include: Sedatives and CNS depressants (benzodiazepines, sleep medications, alcohol): may add to their calming, sedative effect. Thyroid medication (levothyroxine): ashwagandha can raise thyroid hormone levels and may add to thyroid medication, so monitor thyroid labs. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for KSM-66?

NutraSmarts rates the evidence for KSM-66 as Moderate (3 out of 5). It is backed by 7 clinical trials and 12 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(12 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. 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. Journal of the International Society of Sports Nutrition. 2015;12:43. doi: 10.1186/s12970-015-0104-9.PubMedUsed to support: A KSM-66 trial in 57 untrained young men over 8 weeks of resistance training: greater gains in bench-press 1-RM (46.0 kg against 26.4 kg on placebo, p = 0.001) and leg-extension 1-RM (14.5 kg against 9.8 kg, p = 0.04), greater arm and chest size increases, a smaller rise in creatine kinase after exercise, and a greater rise in serum testosterone (96.2 ng/dL against 18.0 ng/dL, p = 0.004). Small, single-centre and manufacturer-linked, and testosterone was a secondary rather than a primary measure.
  2. 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. doi: 10.7759/cureus.6466.PubMedUsed to support: An 8-week three-arm trial in 60 healthy adults with high perceived stress. KSM-66 at 250 mg/day and at 600 mg/day both lowered Perceived Stress Scale scores and serum cortisol and improved sleep quality compared with placebo, the higher dose doing more. Hamilton Anxiety scores fell more than placebo only at 600 mg/day. Sixty participants at one site, with manufacturer-affiliated authorship.
  3. Sharma AK, Basu I, Singh S Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018;24(3):243-248. doi: 10.1089/acm.2017.0183.PubMedUsed to support: In 50 adults with subclinical hypothyroidism (TSH 4.5 to 10 uIU/L), 600 mg/day of ashwagandha root extract for 8 weeks lowered TSH and raised T3 and T4 compared with placebo. This is a small single-centre pilot in a diagnosed thyroid condition, and it is the reason ashwagandha carries a thyroid caution: anyone with a thyroid disorder, or taking levothyroxine or another thyroid medicine, should not take it without medical supervision and thyroid monitoring.
  4. Choudhary D, Bhattacharyya S, Bose S Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. Journal of Dietary Supplements. 2017;14(6):599-612. doi: 10.1080/19390211.2017.1284970.PubMedUsed to support: An 8-week pilot in 50 adults diagnosed with mild cognitive impairment taking 300 mg of root extract twice daily, showing better immediate and general memory on the Wechsler Memory Scale III and better executive function, sustained attention and information-processing speed than placebo. Because every participant had diagnosed cognitive impairment, this does not establish a memory effect in adults with normal cognition.
  5. 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):255-62. doi: 10.4103/0253-7176.106022.PubMedUsed to support: The foundational KSM-66 stress trial: 300 mg of root extract twice daily for 60 days in 64 chronically stressed adults at a single centre. Perceived Stress Scale scores fell 44.0% from baseline against 5.5% on placebo, and serum cortisol fell 27.9% against 7.9%, with both between-group differences statistically significant. Manufacturer-linked, and the percentages are changes from baseline rather than the size of the gap over placebo.
  6. Choudhary B, Shetty A, Langade DG. Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults. Ayu. 2015;36(1):63-8. doi: 10.4103/0974-8520.169002.PubMedUsed to support: A 12-week randomized placebo-controlled trial in 50 healthy athletic adults, and the one cited paper that names KSM-66 in its own abstract. Mean VO2 max rose 5.67 mL/kg/min from baseline against 1.86 on placebo at 12 weeks, and self-reported quality-of-life scores improved. Industry-funded, with 24 and 25 participants completing each arm, and the widely quoted 13.6% is a change from baseline rather than the advantage over placebo.
  7. Dongre S, Langade D, Bhattacharyya S. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study. Biomed Res Int. 2015;2015:284154. doi: 10.1155/2015/284154.PubMedUsed to support: A 50-woman pilot trial in which KSM-66 root extract at 300 mg twice daily for 8 weeks improved Female Sexual Function Index scores, the Female Sexual Distress Scale and the number of successful sexual encounters more than placebo. Single centre, manufacturer-linked, and no hormones were measured, so the reason for the effect is unknown. It is the only trial of its kind, so treat it as preliminary.
  8. Ambiye VR, Langade D, Dongre S, Aptikar P, Kulkarni M, Dongre A. Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. Evid Based Complement Alternat Med. 2013;2013:571420. doi: 10.1155/2013/571420.PubMedUsed to support: A 90-day pilot in 46 men diagnosed with oligospermia, 21 taking KSM-66 root extract at 675 mg/day in three doses and 25 taking placebo. The treated group's within-group changes were a 167% rise in sperm count, a 53% rise in semen volume, a 57% rise in motility and a 17% rise in serum testosterone (4.45 to 5.22 ng/mL), with the paper describing change in the placebo group as minimal. The men had a diagnosed fertility problem, so these figures say nothing about fertile men, and 21 treated participants is a very small sample.
  9. Langade D, Kanchi S, Salve J, Debnath K, Ambegaokar D Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study. Cureus. 2019;11(9):e5797. doi: 10.7759/cureus.5797.PubMedUsed to support: The brand-specific sleep trial: 60 people with insomnia and anxiety took KSM-66 root extract 300 mg twice daily or placebo for 10 weeks, with sleep measured by actigraphy. Sleep onset latency after 10 weeks was 29.00 minutes on the extract against 33.94 on placebo (p = 0.019), and sleep quality, PSQI and Hamilton Anxiety scores improved more than placebo. Sleep efficiency rose from 75.63 to 83.48 on the extract, while the placebo group rose from 75.14 to 79.68. The participants had diagnosed insomnia, and with 40 allocated to the extract at a single Indian centre this is a small study.
  10. 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. doi: 10.1371/journal.pone.0257843.PubMedUsed to support: An independent meta-analysis of five randomized placebo-controlled trials in 400 adults, pooling several different ashwagandha extracts rather than KSM-66 alone. The effect on overall sleep was small but significant (standardized mean difference -0.59, 95% CI -0.75 to -0.42) with substantial variation between trials (I-squared 62%), and was larger in people diagnosed with insomnia, at 600 mg/day or more, and over 8 weeks or longer. Mental alertness on rising and anxiety improved; quality of life did not. The authors note that long-term safety data are limited.
  11. Akhgarjand C, Asoudeh F, Bagheri A, Kalantar Z, Vahabi Z, Shab-Bidar S, Rezvani H, Djafarian K Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials. Phytotherapy Research. 2022;36(11):4115-4124. doi: 10.1002/ptr.7598.PubMedUsed to support: An independent meta-analysis, conducted at Tehran University of Medical Sciences, of 12 randomized trials in 1,002 adults. Ashwagandha supplementation reduced anxiety (standardized mean difference -1.55, 95% CI -2.37 to -0.74) and stress (-1.75, 95% CI -2.29 to -1.22) compared with placebo, with the favourable dose for stress falling in the 300 to 600 mg/day range. Variation between trials was very high (I-squared 93.8% for anxiety, 83.1% for stress) and the authors rated the certainty of the evidence as low for both outcomes, calling for higher-quality studies.
  12. Björnsson HK, Björnsson ES, Avula B, Khan IA, Jonasson JG, Ghabril M, Hayashi PH, Navarro V Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver International. 2020;40(4):825-829. doi: 10.1111/liv.14393.PubMedUsed to support: Five cases of liver injury attributed to ashwagandha-containing supplements, three from Iceland and two from the US Drug-Induced Liver Injury Network, with other causes excluded and causality assessed by structured expert opinion. All five developed jaundice, along with nausea, lethargy, itching and abdominal discomfort, 2 to 12 weeks after starting. The injury pattern was cholestatic or mixed, itching and raised bilirubin lasted 5 to 20 weeks, no one developed liver failure, and liver tests normalized within 1 to 5 months in the four patients followed up. Chemical analysis confirmed ashwagandha in the available supplements. This is a case series, not a trial, and it cannot show how often the reaction occurs.