Ashwagandha: Evidence, Forms, Dosing, and Safety

Ashwagandha: Evidence, Forms, Dosing, and Safety

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Ashwagandha (Withania somnifera) is one of the most extensively studied adaptogenic herbs, with a robust evidence base from multiple meta-analyses supporting benefits for anxiety, stress, cortisol reduction, sleep, testosterone in men, cognitive function, and physical performance. The World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) provisionally recommend it for generalized anxiety disorder. However, most individual trials are small and short-term, and serious safety concerns have emerged — particularly liver injury and thyrotoxicosis. The withanolide content and standardisation of the extract matter significantly for efficacy, with extracts standardised to at least 5% withanolides showing the most consistent benefits.

Table of Contents

Overview

Ashwagandha (Withania somnifera) is an evergreen shrub cultivated in tropical and subtropical areas of Asia, Africa, and Europe. The plant's roots have been used for centuries in Ayurvedic and Unani medicine as an adaptogen — loosely defined as a compound that increases the ability to resist, adapt to, or become resilient against biological, physical, or chemical stressors [1][2][3]. Ashwagandha is also known as "Indian ginseng" (despite no botanical relation to ginseng) and "winter cherry," though it should not be confused with Physalis alkekengi, which shares this common name [4]. The species name somnifera derives from Latin for "sleep-inducing," signifying another traditional use [5].

The root contains a class of steroidal lactones called withanolides, believed to be responsible for many of ashwagandha's pharmacological effects [1][4][6]. Key withanolides include withaferin A and withanolide D [7]. Alkaloids (including withanine and somniferine) and sitoindosides are also present [7]. Withanolide concentrations typically range from 0.001% to 0.5% of dry weight in both roots and leaves, though withaferin A can reach up to 1.6% in leaves [8]. Preclinical research suggests that non-withanolide components may also contribute to ashwagandha's effects [5][9].

The chemical composition of root and leaf differs significantly. Ashwagandha leaf contains substantially more withanone (19 vs. 3 mg/g) and withaferin A (22.31 vs. 0.92 mg/g) than the root [10][11]. This distinction has safety implications: laboratory research suggests withanone may cause DNA damage and liver injury if used in excess or by people with low glutathione levels, and withaferin A has also raised concerns about potential liver effects [10][11]. Most commercial supplements contain root extracts, though some include both root and leaf.

A comprehensive meta-analysis of 23 randomized controlled trials involving 1,706 participants found that ashwagandha supplementation significantly lowered cortisol levels (SMD −1.18, p < 0.04), increased testosterone in men (mean difference 57.43 ng/dL, with no significant increase in women), and reduced anxiety and stress symptoms [12][13]. Among adaptogens, ashwagandha has the most robust evidence base from meta-analyses, particularly compared to Rhodiola rosea, for reducing perceived stress, anxiety, depression, and serum cortisol [12][14][15].

The World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) provisionally recommend ashwagandha root extract (300–600 mg/day, standardised to 5% withanolides) for generalized anxiety disorder, though they note more data are needed for a stronger recommendation [16].

Forms and Bioavailability

Branded Extracts

The clinical literature uses several standardised ashwagandha extracts, each differing in plant parts used, withanolide content, and studied effects.

Extract Manufacturer Plant Part Standardisation Typical Dose Primary Clinical Uses
KSM-66 Ixoreal Biomed Root only ≥5% withanolides 300–600 mg/day Stress, anxiety, sleep, cognition, physical performance, testosterone, fertility
Sensoril Natreon (Kerry) Root + leaf ≥10% withanolide glycosides 125–500 mg/day Stress, anxiety, cognition, physical performance, joint pain
Shoden Arjuna Natural Root + leaf 35% withanolide glycosides 60–240 mg/day Anxiety, sleep, cortisol reduction
NooGandha Specnova Root + leaf 3.5–4% withanolides 225–400 mg/day Cognitive function, stress
Witholytin Verdure Sciences Root 1.5% withanolides 200–400 mg/day Fatigue, stress

Key Differences

KSM-66 is a full-spectrum root-only extract, aligned with traditional Ayurvedic use. It minimises withaferin A content (a cytotoxic withanolide more concentrated in leaves). It is the most extensively studied branded extract, with trials covering stress, anxiety, sleep, cognition, physical performance, testosterone, and fertility outcomes [4][17][18][19].

Sensoril includes both root and leaf, resulting in higher withanolide potency (≥10%), allowing lower effective doses (125–500 mg/day). It tends toward more calming and sedative effects compared to KSM-66, and may be preferred for nighttime use, relaxation, and sleep [20][21]. However, the inclusion of leaf raises the theoretical concern of higher withaferin A and withanone content.

Shoden is enriched in withanolide glycosides (35%), a form with enhanced bioavailability. A pharmacokinetic study found that Shoden achieved approximately 18 times the withanolide blood levels of a regular 2.5% extract calculated to deliver equivalent withanolides, when both were taken on an empty stomach with water only [22]. However, an employee of the manufacturer was among the study authors, and it is unknown how results would differ with food [4][22].

NooGandha is positioned as a nootropic-adaptogen hybrid, emphasising cognitive benefits without sedation. Independent clinical data are more limited compared to KSM-66 or Sensoril [23][24].

Withanolide Content and Quality

The United States Pharmacopeia (USP) requires ashwagandha extracts to contain no less than 2.5% total withanolides. Products should list withanolide content as a percentage or milligram amount. Root powder should contain a minimum of 0.3% withanolides; extracts should contain at least 1.5% [4].

Testing of 25 ashwagandha supplements purchased from Amazon found that 60% failed to contain expected withanolide amounts based on USP standards. Among 16 products that declared withanolide percentages, 9 (56%) contained 69% to 99% less than labelled. All products that passed testing claimed ≤2.5% withanolides, while 8 of the 9 failures claimed 5% to 35% [25].

Pharmacokinetics

Active withanolide compounds have half-lives of approximately 2–10 hours, with averages commonly reported as 6–8 hours. Complete elimination takes approximately 10–50 hours (4–5 half-lives) after a single dose. Absorption is rapid, with peak plasma concentrations typically reached within 1–2 hours. Acute effects (mild relaxation, stress relief) generally last 6–12 hours, while cumulative therapeutic benefits (cortisol reduction, anxiety relief, improved sleep) require consistent daily use over 4–12 weeks [26].

Evidence for Benefits

Anxiety

Clinical evidence consistently supports ashwagandha for reducing anxiety symptoms. Multiple meta-analyses converge on significant anxiolytic effects, particularly at doses of 300–600 mg/day of standardised root extract.

Meta-analyses: A 2024 meta-analysis of 9 RCTs (n=558) found significant reductions in the Perceived Stress Scale (MD = −4.72, 95% CI −8.45 to −0.99), Hamilton Anxiety Scale (MD = −2.19, 95% CI −3.83 to −0.55), and serum cortisol levels (MD = −2.58, 95% CI −4.99 to −0.16) compared to placebo [27]. A 2022 meta-analysis of 12 RCTs (n=1,002) reported significant reductions in anxiety (SMD −1.55, 95% CI −2.37 to −0.74) and stress (SMD −1.75, 95% CI −2.29 to −1.22), with favourable dose-response effects particularly at 300–600 mg/day [28]. A 2026 systematic review and dose-response meta-analysis of 22 RCTs (n=1,391) found significant reductions in anxiety (SMD = −6.87; 95% CI: −8.77 to −4.97), stress (SMD = −5.88), and depression (SMD = −5.68), with dose-dependent effects at 240–1,250 mg/day [29]. A 2021 systematic review of 7 studies (n=491 adults, all from India) found ashwagandha significantly reduced stress and anxiety on validated rating scales, reduced sleeplessness and fatigue, and decreased serum cortisol levels compared to placebo, with benefits appearing greater at doses of 500–600 mg/day [9].

Individual trials: A double-blind study of 75 adults with moderate to severe anxiety found that 300 mg of ashwagandha root extract (1.5% withanolides) twice daily plus a multivitamin for 12 weeks dramatically reduced anxiety and significantly improved fatigue, motivation, and concentration compared to a group receiving psychotherapy plus placebo [30]. A study in 60 adults (mean age 41) with mild anxiety found that 240 mg/day of Shoden extract (84 mg withanolide glycosides) for 2 months produced a greater average decrease in anxiety (−4.2 vs. −2.5 points on a 0–56 scale) and a 23% decrease in morning cortisol (vs. no change for placebo) [31]. A study of 60 adults (mean age 36) with generalized anxiety disorder found that just 60 mg/day of Shoden extract for 60 days reduced anxiety by 59% on the Hamilton Anxiety Rating Scale (vs. an insignificant 0.83% increase for placebo), stress by 48%, and morning cortisol by 65%. A higher dose (120 mg/day) had similar but not significantly greater benefits [32]. A study of adults with GAD found 500–3,000 mg/day for 6 weeks significantly improved anxiety vs. placebo [33]. A 2019 RCT (n=60) found 240 mg/day for 60 days significantly reduced HAM-A scores (P = 0.040) [34].

A study of 130 healthy adults (ages 20–55) with self-reported stress found that a sustained-release ashwagandha root extract (Prolanza, 300 mg containing 15 mg withanolides) taken once daily for 90 days improved stress levels, sleep quality, serum cortisol, psychological well-being, memory, and focus compared to placebo [35]. A study of 54 adults with mild-to-moderate stress and anxiety found 500 mg of ashwagandha root extract (Shagandha, 2.5% withanolides) plus 5 mg piperine daily for 60 days significantly reduced stress and anxiety on two validated rating scales, improved quality of life, multitasking, and concentration compared to placebo [36]. At the University of Colorado, 60 students (ages 18–50) taking 700 mg/day for 30 days reported increased well-being, calm, improved energy, heightened mental clarity, enhanced sleep quality, and more manageable stress compared to placebo [37][38].

Stress and Cortisol

The evidence for stress reduction is closely linked to anxiety outcomes but warrants separate consideration for studies specifically measuring perceived stress and cortisol.

A study in 58 healthy adults (mean age 31) found that KSM-66 at 300 mg twice daily for 2 months produced slightly greater reductions in perceived stress (−8.8 vs. −6 points on a 0–40 scale) and modestly decreased cortisol (−5.5 mcg/dL vs. +0.63 mcg/dL) compared to placebo. A lower dose (125 mg twice daily) did not reduce perceived stress or anxiety [17]. A study in 98 adults (mean age 35) with chronic stress found that Sensoril at 250 mg or 500 mg daily for 8 weeks reduced stress by 13.65 and 15.63 points (vs. 6.46 for placebo on a 0–56 scale). Both doses also significantly reduced anxiety and depression. A 125 mg dose was not effective for stress [20].

Studies with lower withanolide standardisation have not shown significant stress benefits. A study of 111 overweight adults (mean age 54) found that 400 mg/day of Witholytin (1.5% withanolides, providing only 6 mg withanolides/day) for 3 months did not reduce stress, though it slightly decreased fatigue [39]. Similarly, NooGandha (3.5–4% withanolides) at 225–400 mg/day for 30 days did not reduce self-reported stress in one study [23]. These findings suggest extracts standardised to at least 5% withanolides may be necessary for consistent stress benefits [4].

The ashwagandha-cortisol mechanism operates through adaptogenic actions on the hypothalamic-pituitary-adrenal (HPA) axis, normalising HPA hyperactivity during stress. Preclinical studies demonstrate GABAergic mechanisms, including direct agonism of GABA-A receptors and strong agonism at GABA-rho receptors (which show approximately 27 times greater sensitivity to ashwagandha extracts than GABA-A receptors), enhancing inhibitory neurotransmission and further dampening cortisol secretion [7][40].

Sleep

Evidence supports ashwagandha for improving multiple sleep parameters, with benefits most pronounced in people with insomnia.

Meta-analysis: A 2021 systematic review and meta-analysis of 5 RCTs (n=372, all conducted in India) found that ashwagandha had a small but significant effect on sleep quality compared to placebo. Sleep onset latency: effect size −0.53 (95% CI −0.77 to −0.29), I² = 0%. Sleep efficiency improved significantly (SMD −0.68, 95% CI −1.07 to −0.29). In insomniacs specifically, the effect was larger (SMD −0.84, 95% CI −1.10 to −0.58). Benefits were more prominent at ≥600 mg/day and ≥8 weeks duration [41][42].

Individual trials: A study of 58 adults (mean age 39) with insomnia found that KSM-66 at 300 mg twice daily for 10 weeks decreased sleep onset latency by 12.62 minutes vs. 8 minutes with placebo. The increase in total sleep time (7.86 vs. 4.54 minutes) was not statistically significant [43]. A similar study of 73 adults (mean age 37, half with insomnia) found that KSM-66 at 300 mg twice daily for 8 weeks reduced sleep onset latency by 14–15 minutes in insomniacs (vs. 3–5 minutes for placebo), and increased total sleep time by 37 minutes in insomniacs and 9 minutes in non-insomniacs compared to placebo [5][44]. Shoden at 120 mg/day (42 mg withanolides) for 6 weeks improved self-reported sleep quality by 72% vs. 29% for placebo in 150 healthy adults, with objective actigraphy showing 10 vs. 12 minutes onset latency [45]. A study in 58 college students found that 700 mg/day for 30 days modestly improved restorative sleep scores (+16 points on a 100-point scale vs. +10 for placebo), but did not reduce stress or anxious thinking [46].

Cognitive Function

Evidence is mixed, with benefits generally seen at higher withanolide doses (≥30 mg/day) and longer durations (≥8 weeks). Sensoril at 1,000 mg/day (≥100 mg withanolides) for 12 days significantly improved cognitive performance and reaction times in healthy men [47]. KSM-66 at 600 mg/day (30 mg withanolides) for 8 weeks improved memory, executive function, sustained attention, and information processing speed in adults with mild cognitive impairment — but most improvements required the full 8 weeks rather than appearing at 4 weeks [48]. However, a study of 114 adults found the same KSM-66 dosage did not improve spatial memory or processing speed, though episodic memory, working memory, and attention accuracy improved on some measures [49].

NooGandha at 225 mg/day for 1 month did not improve cognitive function in 59 healthy young adults (mean age 22), though it slightly decreased perceived fatigue and tension [24]. Acute ingestion of 400 mg ashwagandha improved executive function, sustained attention, short-term/working memory, and reaction times in healthy young adults, preventing mental fatigue [50]. Repeated supplementation at 225 mg/day for 30 days improved memory (word recall, picture recognition), attention, vigilance, executive function (Stroop test), and reaction time [51]. A systematic review concluded that in most studies, ashwagandha improved performance on cognitive tasks, executive function, attention, and reaction time [52].

Mechanistically, ashwagandha inhibits beta-amyloid plaque formation, enhances acetylcholine levels via increased choline acetyltransferase activity, and modulates serotonin and GABA receptors to reduce neural excitability [53][54][55].

Testosterone and Male Reproductive Health

Ashwagandha has gender-specific effects on testosterone, with significant increases observed in men but not women. The 2026 meta-analysis of 23 RCTs (n=1,706) found ashwagandha significantly increases testosterone in men (mean difference 57.43 ng/dL) with no significant increase in women (mean difference 5.09 ng/dL) [12].

In 46 oligospermic infertile men, 675 mg/day (33.75 mg withanolides) for 90 days produced a 17% increase in serum testosterone, along with increases in sperm count (+167%), semen volume (+53%), and motility (+57%) [56]. In 57 men undergoing resistance training, KSM-66 at 600 mg/day for 8 weeks led to an approximately 15% increase in testosterone, with gains in muscle strength and size and reduced body fat [57]. A crossover study in overweight men aged 40–70 found Shoden (600 mg/day, 21 mg withanolide glycosides) for 8 weeks produced a 14.7% greater testosterone increase vs. placebo, but no significant differences in sexual well-being, vigor, fatigue, cortisol, or estradiol [58].

In healthy men (mean age 39), KSM-66 at 600 mg/day for 8 weeks did not significantly affect total or free testosterone, but modestly increased sexual desire (+14.26 points on a 0–112 scale), improved erectile function (+15.11 points on a 0–75 scale), and increased semen volume (+39%), sperm motility (+16%), sperm concentration (+32%), and total sperm count (+38%) compared to placebo [59]. A 12-month safety study (n=191) showed KSM-66 at 600 mg/day caused small but significant increases in total testosterone (+6.1%) and free testosterone (+7.2%) in men, remaining within normal range [60].

Sexual Function in Women

In 50 women (ages 21–50) with low sexual desire or arousal, KSM-66 at 300 mg twice daily for 2 months significantly improved overall sexual function, arousal, lubrication, and satisfaction vs. placebo, though sexual desire did not significantly improve. No adverse effects were observed [61].

Peri- and Postmenopausal Symptoms

Three studies in India demonstrated benefits for menopausal symptoms. In 123 postmenopausal women (mean age 51), Sensoril at 125 mg or 250 mg twice daily for 6 months improved menopause-specific quality of life, improved biomarkers of bone resorption, and (at the higher dose only) increased bone mineral density at the lumbar spine. Neither dose improved femoral neck bone density [62]. In 91 perimenopausal women (mean age 47), KSM-66 at 600 mg/day for 8 weeks slightly reduced total symptom severity (−3.37 vs. −1.16 points on a 44-point scale), reduced hot flashes by about one per day, increased estradiol, and decreased FSH compared to placebo [63]. In 60 perimenopausal women (mean age 50), KSM-66 at 600 mg/day for 8 weeks improved quality of life by about 12 points (on a 0–44 scale) and reduced perceived stress by about 46% compared to placebo, though hot flash frequency did not significantly decrease [64].

Physical Performance

Results are mixed, with more consistent benefits in untrained individuals and under conditions of high stress. In 40 healthy young adults, 500 mg/day for 8 weeks increased VO2 max, velocity, and leg muscle strength compared to placebo [65]. Sensoril at 500 mg/day (≥50 mg withanolides) for 3 months increased upper and lower body strength in 38 recreationally active young men beginning resistance training [66]. KSM-66 at 600 mg/day for 2 months modestly improved VO2 max during a 12-minute run test and improved exercise recovery in 50 healthy athletic adults [67]. The same dose for 8 weeks increased muscle strength and mass, reduced body fat percentage, and decreased creatine kinase in 57 men undergoing resistance training [57].

A 2026 RCT in 56 semi-professional team sports athletes found KSM-66 at 600 mg/day for 42 days stabilised stress biomarkers, improved recovery perception in females (reduced Hooper Index, DOMS, fatigue), and enhanced lower-body power and pull-ups in males — but testosterone did not change in either sex [68]. However, a study of 30 female professional soccer players found KSM-66 at 600 mg/day for 4 weeks did not significantly improve explosive power, strength, perceived exertion, fatigue, or muscle soreness compared to placebo [69]. A 2021 meta-analysis of 12 RCTs found small-to-moderate positive effects more pronounced in untrained individuals than elite athletes [70].

Body Weight and Metabolism

A 2016 double-blind, placebo-controlled study in chronically stressed adults found that ashwagandha root extract (300 mg twice daily for 8 weeks) led to significant reductions in body weight, BMI, and serum cortisol compared to placebo, alongside improvements in perceived stress and food cravings. These effects appear mediated indirectly through reduced stress-eating and better hormonal balance [71]. Systematic reviews confirm body composition improvements when combined with resistance exercise, with typical fat loss of 1–3% body fat over 8–12 weeks, more pronounced in stressed or overweight individuals [70].

Anti-inflammatory Effects and Joint Pain

In people with knee osteoarthritis, Sensoril at 250 mg or 150 mg twice daily for 12 weeks significantly reduced pain, stiffness, and disability at both doses, with the higher dose showing efficacy at just 4 weeks. No adverse effects were reported, though 20% of the higher-dose group experienced nausea [72].

Thyroid Function

Ashwagandha may increase thyroid hormone levels, which may benefit subclinical hypothyroidism but poses risks for other thyroid conditions. In 50 adults with subclinical hypothyroidism, KSM-66 at 600 mg/day for 8 weeks decreased TSH by 1.85 mIU/L and increased T3 (by 0.5 nmol/L) and T4 (by 18.8 nmol/L) compared to placebo [73]. A study of 3 adult men taking 500 mg/day of a standardised root and leaf extract for 8 weeks showed small increases in T4 levels [74]. The 12-month safety study found KSM-66 at 600 mg/day slightly increased T3 from 123.14 to 132.25 ng/dL (within the normal range of 80–220 ng/dL) [60]. These effects suggest ashwagandha may interact with thyroid medications and affect thyroid hormones even in people without thyroid disease.

Schizophrenia

In 66 adults experiencing worsening schizophrenia symptoms, Sensoril (escalated from 250 mg to 500 mg twice daily, providing ≥100 mg withanolides) for 3 months significantly reduced negative symptoms (emotional flatness, lack of social drive) and general symptoms (anxiety, depression, poor attention) compared to placebo. There was no improvement in positive symptoms (hallucinations, delusions). Sleepiness, epigastric discomfort, and loose stools were more common with ashwagandha [75].

Adjunctive Use in Psychiatric Conditions

Limited research explores ashwagandha as an adjunct to standard psychiatric treatments. A trial in OCD patients on SSRIs found ashwagandha extract (120 mg/day) as add-on significantly improved symptoms over 6 weeks with no adverse events. Secondary analyses from schizophrenia trials showed medium effect sizes favouring ashwagandha for reducing depression and anxiety-depression cluster scores. An open-label study in MDD patients found that combining sertraline with ashwagandha (250 mg twice daily) prevented liver enzyme elevations observed with sertraline alone [76].

Dosing by Indication

No universal recommended dose exists. Effective dosages depend on the extract formulation, withanolide content, and intended use.

Indication Extract Dose Withanolide Content Duration Evidence
Generalized anxiety disorder 300–600 mg/day root extract (5% withanolides) 15–30 mg/day 8–12 weeks WFSBP/CANMAT provisional recommendation [16]
Stress and cortisol reduction 300–600 mg/day root extract ≥15 mg/day 8–12 weeks Multiple positive RCTs and meta-analyses
Sleep improvement 300–600 mg/day root extract; or 120 mg Shoden 15–42 mg/day 6–12 weeks Multiple positive RCTs; ≥600 mg and ≥8 weeks may be optimal [42]
Cognitive function 600–1,000 mg/day extract 30–100 mg/day 8–12 weeks Mixed evidence; higher withanolide doses appear necessary
Testosterone (men) 300–600 mg/day root extract 15–34 mg/day 8–12 weeks Meta-analysis-supported
Male fertility 600–675 mg/day root extract 30–34 mg/day 8–12 weeks Multiple positive RCTs
Physical performance 300–600 mg/day root extract 15–50 mg/day 8–12 weeks Better for untrained individuals
Menopausal symptoms 250–600 mg/day root extract 25–30 mg/day 8 weeks–6 months Multiple positive RCTs
Joint pain (osteoarthritis) 250–500 mg/day Sensoril ≥25–50 mg/day 12 weeks One positive RCT

Practical Dosing Guidance

Starting dose: Begin with 250–300 mg/day and monitor response for 1–2 weeks before increasing [77].

Extract vs. root powder: Clinical trials using root powder (not extract) typically use 3,000–6,000 mg/day [77][78]. The WFSBP/CANMAT recommendation specifically applies to extracts standardised to 5% withanolides.

Withanolide minimum: Look for products providing at least 6 mg of withanolides per serving. Extracts standardised to ≥5% withanolides have the most consistent evidence. Studies using low withanolide standardisation (≤1.5%) have generally not shown significant stress or anxiety benefits [4][39].

Timing: No strong evidence supports a specific time of day. For sleep, taking ashwagandha 1–2 hours before bed may be preferable. For daytime stress management, morning or split dosing (morning and evening) is commonly used. Taking with food may reduce gastrointestinal discomfort [77].

Duration: Most clinical benefits emerge after 4–8 weeks of consistent use. Long-term safety data beyond 3 months are limited, with one 12-month study showing good tolerability [60].

Safety and Side Effects

General Tolerability

Ashwagandha appears well tolerated for short-term use (up to about 3 months). Common side effects are mild and include stomach upset, loose stools, nausea, drowsiness, and headache [9][60][75][79]. Increased heart rate variability has also been reported [39]. Some studies report somnolence rates up to 21% [80]. Evidence on long-term safety beyond 3 months is limited.

Liver Injury

Rare but serious cases of liver injury warrant caution. Five cases (3 men, 2 women, ages 21–62) taking 450–1,350 mg/day for 1 week to 4 months developed jaundice, pruritus, nausea, lethargy, abdominal discomfort, and hyperbilirubinemia, resolving after stopping supplementation [81][82].

Three cases in Iceland (2017–2018) involved NOW brand ashwagandha at 450–1,350 mg/day. Two US cases included one identified as Nature's Way brand. Symptoms occurred 2–12 weeks after starting and resolved in 1–6 months [81].

A 40-year-old man developed jaundice 20 days after starting NOW brand (450 mg/day) despite previously taking 500 mg/day of another brand for a year without issue [83]. A 39-year-old woman developed acute cholestatic hepatitis from 154 mg every other day for 6 weeks, with the pattern suggesting an immune-related response rather than direct toxicity [84]. A review of 8 Indian cases found 5 of 8 occurred in people with chronic liver disease; doses ranged from 500 mg to 20 g/day for 2 weeks to 1.5 years; 3 of those 5 experienced liver failure and died. None of the products contained adulterants [85]. A 2017 case in Japan involved a 20-year-old man who developed liver dysfunction and hyperbilirubinemia while using ashwagandha in combination with multiple antianxiety drugs [86].

Leaf vs. root and liver risk: Ashwagandha leaf contains substantially more withanone (19 vs. 3 mg/g) and withaferin A (22.31 vs. 0.92 mg/g). Laboratory research suggests withanone may cause DNA damage and liver injury in excess or in people with low glutathione levels. There is some concern that withaferin A might adversely affect liver function. A study found that 1,600–4,800 mg/day of root extract containing 4.5% withaferin A elevated liver enzymes in 5 of 11 young cancer patients (though without a placebo control) [10][11].

Until long-term safety studies are completed, ashwagandha (particularly products containing leaf) should not be used by people with liver disease. Those without liver disease should use caution with high-withanolide products.

Thyroid Effects

Ashwagandha can increase thyroid hormone levels, which may benefit subclinical hypothyroidism but poses risks for others. Cases of thyrotoxicosis include: a woman in the Netherlands taking ashwagandha capsules for several weeks [87]; a 62-year-old woman taking 1,950 mg/day of root extract plus 15 mg black pepper for 2 months who developed thyroid enlargement, anxiety, weight loss, weakness, increased heart rate, and mild anaemia — all resolving approximately 1 month after stopping [88]; and a 47-year-old Japanese man who developed painless thyroiditis approximately 2 months after starting ashwagandha, with symptoms normalising 7 weeks after stopping [89].

Denmark banned ashwagandha in 2023 based on concerns about thyroid and sex hormone effects [90]. The French Agency for Food, Environmental, and Occupational Health and Safety (ANSES) recommended against use by pregnant and breastfeeding women and people with endocrine disorders [91]. The German Federal Institute for Risk Assessment (BfR) highlighted potential health risks including liver toxicity and hormonal effects [92].

Adrenal Effects

A 2022 case report described reversible adrenal insufficiency after 10 weeks of ashwagandha supplementation (21.4 mg withanolides daily), with blunted cortisol response on Synacthen testing that normalised after 2 weeks of discontinuation [80].

Pregnancy and Reproductive Concerns

Some experts advise against ashwagandha use during pregnancy due to reports suggesting potential abortifacient effects [9][93][94]. However, the American Herbal Pharmacopoeia (AHP) has stated their 2000 monograph has been misrepresented and that there is no evidence ashwagandha root causes abortions [95]. Given insufficient evidence on safety during pregnancy, most authorities recommend against use by pregnant and breastfeeding women.

Other Safety Concerns

  • Nightshade allergy: Ashwagandha belongs to the Solanaceae (nightshade) family. People allergic to potato, eggplant, tomato, or peppers could potentially experience allergic reactions [4].
  • Blood sugar: Ashwagandha may lower blood sugar levels and should be used cautiously by people with diabetes or hypoglycaemia [96].
  • Blood pressure: Preliminary research suggests ashwagandha could lower blood pressure, requiring caution in those with hypotension or on antihypertensive medications [4].
  • Cardiac rhythm: Dizziness, rapid heartbeat (ventricular tachycardia), and fainting have been reported in two middle-aged men, though details about the ashwagandha source and dose were lacking [97].
  • Skin reactions: Burning, itching, and discoloration of penile skin was reported in a man taking 5 g of root powder daily for 6 days, consistent with a fixed drug eruption that resolved on discontinuation [98].
  • Withdrawal effects: Isolated case reports describe anxiety, tachycardia, insomnia, or acute psychosis-like episodes following abrupt cessation after long-term use, though these are rare and may reflect underlying condition recurrence rather than true dependence [80].
  • Emotional blunting: Reports of brain fog, emotional dullness, and anhedonia appear on online platforms, particularly with prolonged or high-dose use. These are not established as adverse effects in clinical studies, and expert analyses confirm no human studies support these as common effects, though preclinical mechanistic hints (serotonin receptor modulation, cortisol suppression) offer theoretical plausibility for idiosyncratic responses [80].

Drug Interactions

Ashwagandha can interact with several medication classes through pharmacodynamic or pharmacokinetic mechanisms.

Medication Class Interaction Clinical Concern
Sedatives/Benzodiazepines May potentiate sedation via GABAergic activity Excessive drowsiness or respiratory depression [76][93]
Thyroid medications (levothyroxine) Increases thyroid hormone production Excessive levels; thyrotoxicosis risk [73][93]
Immunosuppressants (tacrolimus, cyclophosphamide) May stimulate immune activity Reduced efficacy; case report of kidney transplant rejection [99]
SSRIs (escitalopram, sertraline) May increase serotonin; possible CYP2D6/CYP3A4 inhibition Theoretical serotonin syndrome risk; one case report with escitalopram [100][101]
Antihypertensives/Beta-blockers May further lower blood pressure Theoretical hypotension risk; no clinical reports [4]
Antidiabetic medications May lower blood sugar Hypoglycaemia risk when combined [96]
Blood thinners (warfarin, aspirin, clopidogrel) Preliminary evidence of blood-thinning effects Use with caution pending further research [102]
Anesthesia Sedating effects Discontinue prior to surgery [4]

Serotonin syndrome case: A 22-year-old woman developed symptoms of serotonin syndrome (uncontrolled limb movement, eyelid flutter, fever, vomiting, pupil dilation, fast heart rate) 2 days after taking 600 mg ashwagandha (pill) plus 1,520 mg (as tea) along with escitalopram 10 mg daily. She recovered after discontinuing both and receiving benzodiazepines and supportive care [100].

Transplant rejection case: A 69-year-old kidney transplant recipient who had been stable for 2 years on tacrolimus, mycophenolate, and prednisone developed acute organ rejection requiring kidney removal 2 weeks after beginning ashwagandha supplementation [99].

Autoimmune trigger: Due to its immune-stimulating effects, ashwagandha might also trigger symptoms in people with autoimmune conditions. A woman with coeliac disease and systemic sclerosis developed optic neuritis about 2 weeks after starting ashwagandha, resolving with corticosteroid treatment and cessation of supplementation [103].

Dietary Sources

Ashwagandha is not a nutrient found in common foods. It is available exclusively as a supplement derived from the roots (and sometimes leaves) of the Withania somnifera plant. Traditional preparations include:

  • Powdered root mixed with warm milk — the classic Ayurvedic preparation, believed to enhance absorption
  • Churna — fine root powder, often combined with ghee or honey for enhanced absorption and to target specific dosha imbalances
  • Root powder — 3–6 g/day in traditional practice, divided into 2–3 doses
  • Standardised extracts — the most common modern form, available as capsules, tablets, or powder

Commercial forms include capsules, powders, tinctures, gummies, and topical preparations. Standardised root extracts (KSM-66, Sensoril, Shoden) are preferred for reliability and clinical evidence. Products should list withanolide content and ideally carry third-party testing verification [4][77]. The plant grows in dry, arid, and subtropical climates, primarily in India, North Africa, the Middle East, and southern Europe. It is harvested 180–210 days after seeding, with roots shade-dried and processed via solvent extraction, chromatographic purification, and HPLC standardisation to ensure consistent withanolide content [104].

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