Ashwagandha
Withania somnifera
Ashwagandha (Withania somnifera) is a root-derived botanical adaptogen sold as a dietary supplement, standardized to withanolide content (e.g., Shoden, KSM-66, Witholytin extracts). It is used mainly for stress, anxiety, sleep, fatigue, and (in the bodybuilding/hormonal-support context) for modest increases in testosterone and perceived recovery. Human RCTs support small-to-moderate reductions in perceived stress, morning cortisol, and anxiety scores, and modest testosterone increases in some male populations. The main risk is hepatotoxicity: multiple well-documented cases of cholestatic or mixed drug-induced liver injury (jaundice, pruritus, severe hyperbilirubinemia), including at least one case progressing to acute-on-chronic liver failure and a reported liver transplant. It can also trigger thyrotoxicosis/painless thyroiditis and may raise thyroid hormone levels. It is not an anabolic steroid and does not suppress the reproductive axis, but it is not benign: because it is an unregulated supplement with real organ-level risks and variable product quality, it should be treated as a drug, monitored with bloodwork, and stopped immediately if signs of liver injury appear. Educational information only; not medical advice. 21+.
Mechanism of action
Pharmacokinetics
Not well characterized in humans. Robust human pharmacokinetic data for withanolides/withaferin A are lacking; a defined plasma half-life cannot be reliably stated from primary human literature.
Clinical trials dose once or twice daily (e.g., 240-300 mg once daily, or 200-300 mg twice daily), implying an effective duration on the order of 12-24 hours per dose, but this is inferred from dosing regimens rather than measured PK. Clinical endpoints (cortisol, mood, hormones) are assessed over weeks of continuous use, not single doses.
Oral (capsules/tablets of standardized root or root/leaf extract).
Presumed hepatic metabolism of withanolides; specific human metabolic and clearance pathways are not well defined in the primary literature. The documented pattern of idiosyncratic cholestatic/mixed liver injury indicates hepatobiliary involvement. This PK information is provided for washout reasoning and clinician discussion, not for evading any test.
For monitoring and washout planning, not drug-test evasion.
Physiological & performance effects
- Small-to-moderate reduction in perceived stress and anxiety scores (e.g., Hamilton Anxiety Rating Scale) versus placebo in stressed adults over 8 weeks in some RCTs, though not all trials show separation from placebo on the primary stress endpoint.
- Reduction in morning cortisol and DHEA-S versus placebo in at least one RCT of stressed adults.
- Small but statistically significant improvement in sleep quality/quantity in a meta-analysis of RCTs, most pronounced at doses >=600 mg/day for >=8 weeks and in people diagnosed with insomnia.
- Modest increases in serum/salivary testosterone reported in several male RCTs (resistance-trained young men, aging overweight men, men with low libido), though magnitude is small and one stress RCT found no significant between-group testosterone difference.
- Increased free testosterone and luteinizing hormone in overweight middle-to-older men in one RCT; increases in DHEA-S in aging men.
- Improvements in subjective sexual well-being scores in men and in male infertility parameters (sperm concentration, motility, volume) in a systematic review, though largely from small/observational studies.
- Modest increases in muscle strength, muscle size, and reductions in body-fat percentage and exercise-induced creatine kinase in one resistance-training RCT.
- In perimenopausal women, reduced menopausal symptom scores with increased estradiol and reduced FSH/LH.
- Reduction of anxiety symptom scores as an adjunct in some psychiatric contexts (e.g., signal for symptom reduction in schizophrenia augmentation network meta-analysis, low-quality evidence).
Adverse effects by system
No consistent adverse cardiovascular signal in RCTs; trials report good tolerability without notable blood-pressure or cardiac events. One RCT reported an increase in heart rate variability (interpreted as autonomic, not adverse). Cardiovascular safety at high doses or long term is not well studied.
The most serious documented harm. Multiple case reports and case series describe idiosyncratic drug-induced (herb-induced) liver injury: cholestatic or mixed pattern with jaundice, marked pruritus, nausea, lethargy, and prolonged hyperbilirubinemia, typically after 2-12 weeks of use. Most cases are self-limited with normalization in 1-5 months after stopping, but severe outcomes including acute-on-chronic liver failure and a reported liver transplant have occurred, especially with pre-existing liver disease.
Not suppressive to the reproductive axis; if anything modestly stimulatory to testosterone/DHEA in some male trials and alters estradiol/FSH/LH in perimenopausal women. Endocrine risk is chiefly thyroidal: cases of thyrotoxicosis and painless thyroiditis have been reported, and the herb may raise thyroid hormone levels, which is hazardous in people with hyperthyroidism or on thyroid medication.
In males, associated with increased testosterone and improved semen parameters in some studies (an intended effect, but hormonal alteration is still a physiological change to monitor). In females, alters estradiol/FSH/LH. Traditionally regarded as abortifacient/uterine-stimulant and is contraindicated in pregnancy; adequate human reproductive-safety data in pregnancy and lactation are lacking.
Generally associated with reduced anxiety/stress scores rather than psychiatric harm in trials. However, thyrotoxicosis (a documented risk) can present with anxiety, agitation, and insomnia, and mania/agitation is a theoretical concern in susceptible individuals. Dedicated psychiatric safety data are limited.
No established renal toxicity signal in the human literature; renal safety has not been specifically or adequately studied, so absence of reports is not evidence of safety.
No consistent hematologic toxicity reported in RCTs. Hyperbilirubinemia occurs in the context of liver injury but reflects hepatobiliary rather than primary hematologic pathology. Hematologic safety is not specifically well studied.
Pruritus (itching) is a prominent feature of ashwagandha-associated cholestatic liver injury. Isolated primary skin reactions are otherwise not well characterized in the human literature.
HPTA suppression & recovery
Suppression: None expected — ashwagandha is not an androgen or a hormonal suppressant and does not suppress the hypothalamic-pituitary-gonadal axis. In male RCTs it is associated with modest increases in testosterone, free testosterone, LH, and DHEA-S rather than suppression [PMID 30854916, PMID 37740662, PMID 26609282].
Because ashwagandha does not suppress the HPT axis, post-use SERM recovery protocols are not applicable and are out of scope here. This monograph does not describe any SERM protocol. If ashwagandha is combined with hormonally active agents, or if abnormal hormone or thyroid labs, gynecomastia, or symptoms of hyper-/hypothyroidism appear, evaluation and any recovery management should be directed by an endocrinologist. Recovery from a thyroiditis episode is variable and clinician-directed.
Monitoring
Cadence: Baseline before starting; recheck liver panel around 4-8 weeks (the typical latency window for injury) and if any symptoms arise; thereafter periodically during continued use. Any abnormal or rising liver enzymes/bilirubin warrant stopping and clinician review.
- Jaundice (yellowing of skin or eyes)
- Dark urine or pale stools
- Itching (pruritus)
- Nausea, vomiting, loss of appetite, right-upper-abdominal discomfort
- Unusual fatigue or lethargy
- Palpitations, heat intolerance, tremor, unexplained weight loss, or worsening anxiety/insomnia (possible thyrotoxicosis)
Contraindications
- Pre-existing liver disease or unexplained elevated liver enzymes (risk of severe/decompensated liver injury).
- Concurrent use of other hepatotoxic drugs, supplements, or heavy alcohol use.
- Hyperthyroidism or thyroid disease, or use of thyroid hormone medication (risk of thyrotoxicosis/thyroid hormone elevation).
- Pregnancy and breastfeeding (traditionally considered abortifacient; inadequate safety data).
- Autoimmune conditions (immunomodulatory activity; use cautiously and under clinician guidance).
- Scheduled surgery / anesthesia (potential sedative and hormonal effects; discontinue in advance per clinician advice).
- Known hypersensitivity to Withania somnifera or nightshade (Solanaceae) family plants.
- Combination with sedatives, benzodiazepines, or other CNS depressants (additive sedation).
Interaction profile
- ContraindicatedWith DNP: Additive cardiovascular strain
Check a specific combination in the interaction checker.
Reducing harm & when to stop
- Treat ashwagandha as a drug with real organ-level risk, not a harmless herb; product quality and withanolide content vary widely and are not tightly regulated.
- Get baseline liver function tests before starting and recheck at roughly 4-8 weeks and if any symptoms appear — this is the typical window for herb-induced liver injury.
- Stop immediately and seek medical care for any jaundice, dark urine, pale stools, itching, nausea, right-upper-abdominal pain, or unusual fatigue — these can signal liver injury that occasionally becomes severe.
- Avoid entirely if you have pre-existing liver disease, elevated liver enzymes, or drink heavily; do not stack with other hepatotoxic drugs or supplements.
- Watch for thyroid symptoms (palpitations, heat intolerance, tremor, weight loss, worsening anxiety/insomnia) and avoid if you have thyroid disease or take thyroid medication without endocrinologist oversight.
- Do not use in pregnancy or while breastfeeding.
- Because it can raise testosterone/DHEA and alter thyroid and reproductive hormones, monitor bloodwork with a clinician rather than assuming a supplement cannot change your labs.
- Disclose ashwagandha use to your physician, anesthesiologist, and pharmacist; discontinue before scheduled surgery per medical advice.
- This is not a performance-optimization protocol: any hormonal or thyroid changes should prompt clinician review, and management of abnormal results should be directed by an endocrinologist.
Citations (15)
Every clinical claim above is tied to a primary source. Overall evidence grade C — graded to the best available evidence for its core claims.
- 01
In stressed adults, ashwagandha (240 mg/day standardized extract) over 60 days significantly reduced Hamilton Anxiety scores and morning cortisol and DHEA-S versus placebo; testosterone rose in males over time but was not significantly different from placebo.
RCTAn investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.PMID 31517876 ↗
- 02
In overweight/mildly obese adults with stress and fatigue, 200 mg twice-daily ashwagandha (Witholytin) did not significantly beat placebo on perceived stress but reduced fatigue and increased heart rate variability; in men it significantly increased free testosterone and LH.
RCTExploring the efficacy and safety of a novel standardized ashwagandha root extract (Witholytin) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial.PMID 37740662 ↗
- 03
In resistance-trained young men, 300 mg twice-daily ashwagandha root extract over 8 weeks increased muscle strength and size, reduced body-fat percentage and exercise-induced creatine kinase, and increased serum testosterone versus placebo.
RCTExamining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial.PMID 26609282 ↗
- 04
In aging overweight men, 8 weeks of standardized ashwagandha (Shoden, 21 mg withanolide glycosides/day) increased DHEA-S and testosterone versus placebo, with no significant change in cortisol or estradiol and no significant subjective benefit.
RCTA Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha in Aging, Overweight Males.PMID 30854916 ↗
- 05
In adult men with low sexual desire, 300 mg twice-daily ashwagandha root extract over 8 weeks improved sexual well-being scores and increased serum testosterone versus placebo, with no change in prolactin.
- 06
In perimenopausal women, 300 mg twice-daily ashwagandha reduced menopausal symptom scores and increased serum estradiol while lowering FSH and LH; testosterone did not differ significantly between groups.
- 07
A systematic review/meta-analysis in men reported improved semen parameters and hormonal profile with Withania somnifera, but concluded the evidence base is small and insufficiently robust; no adverse effects were reported in the included infertile men.
Meta-analysisWithania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis.PMID 30466985 ↗
- 08
A meta-analysis of 5 RCTs (400 participants) found a small but significant improvement in sleep with ashwagandha, greatest at >=600 mg/day for >=8 weeks and in people with insomnia; it noted limited long-term safety data.
Meta-analysisPMID 34559859 ↗
- 09
A network meta-analysis of medicinal herbs for anxiety found Withania somnifera reduced Hamilton Anxiety scores but was limited by small sample sizes; herbs were generally well tolerated.
Meta-analysisPMID 35378276 ↗
- 10
A schizophrenia augmentation network meta-analysis found a symptom-reduction signal for Withania somnifera in the low-risk-of-bias acute-phase subset, but overall evidence quality was low to very low.
Meta-analysisPMID 39026098 ↗
- 11
Ashwagandha can cause idiosyncratic drug-induced liver injury: a 5-case series (Iceland + US DILIN) described cholestatic or mixed injury with jaundice and prolonged pruritus after 2-12 weeks, self-limited with normalization in 1-5 months.
Case seriesAshwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network.PMID 31991029 ↗
- 12
RUCAM-assessed case reports rated ashwagandha hepatotoxicity as 'probable' (hepatocellular and mixed patterns) and noted prior published cases including one that resulted in liver transplantation.
Case reportHerb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause.PMID 37631044 ↗
- 13
Ashwagandha can precipitate life-threatening acute-on-chronic liver failure, particularly in individuals with pre-existing liver conditions.
Case reportChanging perspectives: unveiling the risks of ashwagandha-induced hepatotoxicity.PMID 37982556 ↗
- 14
A narrative review of Ayurvedic (Ayush) herbs identifies Withania somnifera among agents with inherent hepatotoxic potential that can rarely progress to acute or acute-on-chronic liver failure.
ReviewPMID 38640296 ↗
- 15
Ashwagandha can cause thyrotoxicosis: a case of painless thyroiditis developed after two months of use and resolved after discontinuation.
Case reportPMID 38559552 ↗
Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice