Scientific Name(s): Withania somnifera (L.) Dunal.
Common Name(s): Ajagandha, Amangura, Amukkirag, Asgand, Ashvagandha, Asundha, Asvagandha, Aswaganda, Indian ginseng, Kanaje Hindi, Kuthmithi, Samm al ferakh, Winter cherry, Withania
Medically reviewed by Drugs.com. Last updated on Dec 13, 2021.
Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Trials supporting its clinical use are limited; however, many in vitro and animal experiments suggest effects on the immune, endocrine, and CNS systems, as well as in the pathogenesis of cancer and inflammatory conditions. Limited data suggest benefit for anxiety and sleep quality.
Dosing information is limited. W. somnifera root powder has generally been used at daily dosages of 120 mg to 2 g in combination with other preparations.
Contraindications have not been identified.
Abortifacient properties have been reported for ashwagandha. Avoid use.
None well documented.
Limited clinical trials are available and case reports are lacking. Cases of ashwagandha-induced liver injury have been reported.
Acute toxicity of W. somnifera is modest; at reasonable doses, ashwagandha is nontoxic.
- Solanaceae (nightshade)
W. somnifera is an erect, greyish, slightly hairy evergreen shrub that grows to about 1.5 m in height and has fairly long tuberous roots. It is widely cultivated in India and throughout the Middle East and is found in eastern Africa. The small and greenish-yellow flowers can be single or in clusters. The fruit is smooth, round, and fleshy, with many seeds; it is orange-red when ripe and enclosed in a membranous covering.1 A synonym is Physalis somnifera L.
The root of W. somnifera is used to make the Ayurvedic tonic ashwagandha, which has been translated to "smells like a horse."2 Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Other parts of the plant (eg, seeds, leaves) have been used as a pain reliever, to kill lice, and in making soap. The fresh berries have been used as an emetic.2, 3
The principal bioactive compounds of W. somnifera are withanolides, which are triterpene lactones. More than 40 withanolides, approximately 12 alkaloids and several sitoindosides have been isolated and identified from W. somnifera. The withanolides are structurally related to the ginsenosides of Panax ginseng, hence the common name "Indian ginseng."3, 4 Withanine and somniferine are among the alkaloids.67 Chemical constituents for the roots, fruits, seeds, and stem include withanone; withaferin A; withanolides A, D, an G; and sitoindosides IX, X, VII, and VIII. High performance liquid chromatography techniques to quantify constituents have also been established.2, 3, 4
Uses and Pharmacology
Well-designed clinical studies in which W. somnifera or its extracts are used as a single agent are limited.
Animal and experimental data
In vitro and animal experiments suggest W. somnifera may possess anti-inflammatory properties. Cultures of cartilage from patients with osteoarthritis and rheumatoid arthritis have been used to demonstrate W. somnifera's protective effects on chondroplasts.(8, 9, 10, 11) Related effects on cytokines and transcription factors, and suppression of nitric oxide have also been demonstrated.(12) In experiments in rats with induced inflammation, decreased inflammation (paw volume), pain, and disability were noted, as well as an antipyretic effect after administration of W. somnifera root powder. The ulcerogenic effect of W. somnifera was lower than that of indomethacin.(4, 13, 14, 15, 16)
A small clinical study evaluating a combination therapy that included ashwagandha demonstrated decreased pain and disability in arthritis, while no changes were observed in the erythrocyte sedimentation rate.(3, 4)
Animal and experimental data
Despite more than 30 years of research into a potential role for W. somnifera extracts in the treatment of cancer, clinical trials are lacking. In vitro and animal experiments have been conducted using whole plant extract, ethanol root extracts, aqueous and methanolic leaf extracts, individual withanolides, and withaferin A. Human cancer cell line investigations include HL-60 leukemic and myeloid leukemia cell lines, and bladder, breast, prostate, colon, kidney, gastric, and lung cancer cell lines. Mechanisms of action described include antiproliferative effects, apoptosis, radio-sensitization, mitotic arrest, antiangiogenesis, and enhancement of cell defense mechanisms.(4, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29) Limited studies suggest withanone, withaferin A, and withanolide A have protective effects on glioma cell lines, as well as human fibroblasts, and thereby slow senescence.(30, 31)
Experiments in mice have demonstrated decreased lung adenoma tumor incidence with whole plant extract and complete regression of mouse sarcoma tumor with ethanol root extract, as well as radio-sensitizing of carcinomas and increased apoptosis of human breast cancer cells by withaferin A, a steroidal lactone of W. somnifera.(4, 24)
In vitro studies and experiments in animals suggest CNS effects, including modulation of acetylcholinesterase and butyrylcholinesterase activity, inhibition of calcium ion influx, blockade of gamma-aminobutyric acid receptors, modulation of 5-HT1 and 5-HT2 receptors, antioxidant activity, and regeneration of neurites(4, 6, 11) with some researchers suggesting potential applications in Alzheimer and Parkinson diseases.(3, 5, 6)
Withania extract protected against pentylenetetrazol-induced seizures in a mouse anticonvulsant model when administered over a 9-week period.(34) The same research group found the extract active in a rat status epilepticus model.(35) A depressant effect on the CNS was indicated by potentiation of pentobarbital effects on the righting reflex in mice(36) and a mild tranquilizing/relaxant effect in monkeys, cats, dogs, rats, and mice by a total alkaloid extract from the plant roots.(4)
A further study of the extract found that it inhibited the development of tolerance to morphine in mice, while suppressing withdrawal symptoms precipitated by naloxone.(37) A withanolide-containing fraction reversed morphine-induced reduction in intestinal motility and confirmed the previous finding of inhibition of development of tolerance to morphine.(38) A role in the management of drug addiction has been suggested.(11)
An experiment supported the traditional Ayurvedic medicinal claim that the plant's use could be attributed to effects on learning and memory. Ibotenic acid-induced lesions in intact rat brain that led to cognitive deficit, as measured by performance in a learning task, were reversed by treatment with a withanolide mixture.(39)
Following animal studies that revealed significant serotonergic effects of W. somnifera root extract, Iranian researchers conducted a double-blind, randomized, placebo-controlled trial (n=30) to investigate its effects on symptoms of obsessive-compulsive disorder (OCD). All patients were being treated with selective serotonin reuptake inhibitors (SSRIs). A significant difference was observed in baseline OCD scores between the groups with a mean of 26 (range, 14 to 40) in the treatment group and 18 (range, 11 to 33) in placebo (P=0.038). After 6 weeks, a significantly greater reduction in mean OCD symptom scores was observed in the treatment group (−8) compared to placebo (−2) (P<0.001). W. somnifera root extract was administered as 30 mg capsules and titrated up to 4 capsules daily over approximately 2 weeks (to reduce likelihood of GI side effects), then after 2 weeks, the dose was tapered down again over an approximate 2-week period. No side effects were reported.(67)
Limited trials in elderly populations using traditional combination therapies showed mixed results. One study of 2 g of root extract twice daily (in combination) administered over 6 months made no difference in sleep onset times or duration.(40) In another study, increased balance was determined in elderly patients with long-term progressive degenerative ataxia.(41) In a double-blind, randomized, placebo-controlled study, ashwagandha root extract 300 mg twice daily or placebo was administered to 50 outpatients (65 to 80 years of age; body mass index [BMI], 22 to 32) for 12 weeks to assess effects on quality of life (QOL) and sleep parameters. Improvements from baseline were significantly better with ashwagandha compared to placebo in the total QOL score (P<0.0001), as well as 4 of the 5 individual domains (ie, global, physical, psychological, environment). Improvement in the social relationship domain was not significantly different between groups. Compared to placebo, additional benefit was observed with treatment for "mental alertness on rising" (P<0.05) and for "sleep quality" (P<0.0001). The improvement in total sleep scores, however, was not significantly different between groups. Treatment was well tolerated with no adverse events reported.(73) In 60 predominantly male patients with insomnia (18 to 60 years of age; BMI, 16.5 to 30), ashwagandha root extract 300 mg or placebo was administered twice daily for 10 weeks in a double-blind, randomized, controlled study. Significant improvements from baseline were observed with treatment compared to placebo in mean sleep onset latency time (−13 vs −8 minutes; P=0.019), sleep efficiency scores (+7.9 points vs +4.5 points; P<0.0001), subjective measures of sleep quality (−3.9 points vs −1.6 points; P<0.0001), and anxiety scores (−5.1 points vs −1.9 points; P=0.002). Improvements in total sleep time, wake after sleep onset, total time in bed, and mental alertness on rising were not significantly different between groups. No adverse events were reported during the study period.(77)
A systematic review of human trial evidence for W. somnifera as treatment for anxiety and stress identified 5 randomized controlled trials (n=64 to 130). Dosages ranged from 125 to 12,000 mg/day. In general, favorable results were observed compared with placebo, with 4 trials documenting significant differences. Additionally, no significant adverse effects were reported. However, the quality of results was very limited due to nonblinding, conflicts of interest, and only patient-reported outcomes; risk of bias was probably moderate to high.(66) In a double-blind, randomized, placebo-controlled trial that administered standardized ashwangandha 240 mg/day (35% withanolide glycosides) or placebo to 60 healthy men and women, clinician-rated anxiety scores improved significantly in both the treatment and placebo groups (41% and 24%, respectively) with ashwagandha providing significantly better scores than placebo (P=0.04). Self-reported scores on the depression-anxiety-stress scale also improved significantly within each group (30% and 10%, respectively); however, no significant difference was observed between groups.(75) In patients with a diagnosis of schizophrenia (61%) or schizoaffective disorder (39%), secondary outcome analysis of a 12-week, double-blind, randomized, placebo-controlled study (N=66) looked at the effect of standardized W. somnifera extract on depression and anxiety symptoms. At week 2, the dose was titrated up from 250 mg to a final dose of 500 mg twice daily. A statistically significant improvement was reported for both the depression single-item score and the depression-anxiety cluster score (P=0.011 for each) favoring treatment over placebo. No significant difference was observed between groups in adverse events; somnolence, diarrhea, and stomach pain were more common with ashwagandha.(72)
Adjunctive use of W. somnifera 500 mg/day in patients with bipolar disorder has demonstrated significant improvements in memory, reaction time, and social cognition in a preliminary study.(69) In outpatients with mild cognitive impairment, a double-blind, randomized, placebo-controlled pilot study (N=50) reported that ashwagandha root extract 300 mg twice daily for 8 weeks led to statistically significant improvements in several immediate memory as well as general memory subtest scores compared to placebo. Specifically, logical memory, verbal paired associates, and family pictures scores were enhanced. Immediate memory of faces was also significantly improved with treatment. Additionally, significant benefit was observed for both executive function as well as attention and information processing speed at both 4 and 8 weeks. However, inconclusive and no significant effect were reported for working memory and for visuospatial processing and response, respectively. Treatment was well tolerated with no adverse events reported and no negative effects on vital parameters.(71)
Fatigue and stress
The effect of standardized ashwagandha extract (35% withanolide glycosides) on fatigue, vitality and associated steroid hormonal systems in healthy aging, overweight men (40 to 70 years of age; BMI, 25 to 35) was investigated via a 16-week, double-blind, randomized, placebo-controlled crossover trial (N=57). A dose of 600 mg/day of ashwagandha extract delivered 21 mg/day of withanolide glycosides; no washout period was employed between treatments. Results from the 43 participants who comprised the per-protocol population demonstrated no significant differences between treatments in symptom scores for fatigue and vigor. However, significant increases in dehydroepiandrosterone sulfate (DHEA‑S) (+1.49 nmol/L; P=0.005) and testosterone (+45.59 pmol/L; P=0.01) were observed during the ashwagandha period compared to placebo, which were not sustained over the 8-week placebo period. The decreases in estradiol and cortisol were not significantly different from the placebo period. Treatment was well tolerated with no adverse events reported and no drop-outs due to side effects.(74)
Another study conducted in males and females assessed the effects of ashwagandha on stress, anxiety, and hormone production. Standardized ashwangandha 240 mg/day (35% withanolide glycosides) or placebo was administered once daily for 60 days in healthy adults (18 to 65 years of age; BMI 24 to 27) in a double-blind, randomized manner (N=60). Clinician-rated anxiety scores improved significantly in both the treatment and placebo groups (41% and 24%, respectively), with ashwagandha providing significantly better scores than placebo (P=0.04). Self-reported scores on the depression-anxiety-stress scale also improved significantly within each group (30% and 10%, respectively); however, no significant difference was observed between groups. Effect of gender on these primary outcomes was not reported. Secondarily, significant reductions were observed overall for ashwagandha compared to placebo on levels of cortisol (P<0.001) and DHEA-S (P=0.004) with a non-significant increase in testosterone. Within the male and female subgroups, cortisol reductions with ashwagandha compared to placebo were significant in both males (P=0.011) and females (P=0.02); however, DHEA-S reductions were significant only in males (P=0.046), and the increases in testosterone were not statistically significant in either subgroup. Treatment was well tolerated with no adverse events reported and no changes on full blood counts or lipid parameters observed.(75)
Immune system effects
Withanolides inhibit murine spleen cell proliferation(42) and an extract of W. somnifera reversed ochratoxin's suppressive effect on murine macrophage chemotaxis.(43) Withanolide glycosides activated murine macrophages and phagocytosis, and increased lysosomal enzymatic activity secreted by the macrophages, while also displaying antistress activity and positive effects on learning and memory in rats.(44) Alpha-2 macroglobulin synthesis stimulated by inflammation was reduced by W. somnifera extract.(45) Similarly, the extract prevented myelosuppression caused by cyclophosphamide, azathioprine, or prednisolone in mice.(46)
In a clinical study, ashwagandha 6 mL root extract administered twice daily for 4 days resulted in increases in CD4 expression, as well as activation of natural killer cells.(47) Additional effects on cytokines and the complement system, lymphocyte proliferation, and humoral and cell-mediated responses have been discussed.(48)
In 50 healthy men (mean age, 28.5 years), ashwagandha root extract 300 mg (5% withanolides) consumed twice daily for 8 weeks resulted in significantly greater increases in muscle strength in both the upper (+46.05 kg vs +26.42 kg; P=0.001) and lower body (+14.05 kg vs +9.77 kg; P=0.04) compared to placebo, respectively. Muscle size also increased significantly with ashwagandha but only in the arm (P=0.01) and chest (P<0.001), not in the thigh. Additionally, fat percentage improvement (−3.47% vs −1.52%) and muscle recovery decreased more with treatment than the placebo (P=0.03 for both). The increase in serum testosterone was not significantly different than placebo.(76)
Animal experiments have been conducted to describe adaptogenic properties (increased swimming endurance and reduced stress response) of W. somnifera. Individual clinical trials to support this effect are lacking.(49, 50, 51, 52, 53, 54, 55, 56, 57) However, a meta-analysis of 4 low-quality randomized controlled trials documented a significant mean difference in VO2max with ashwagandha supplementation of 300 to 500 mg/day when given to healthy adults for 2 to 12 weeks.(70)
Effects on aging have been promoted, based on claims regarding increased hemoglobin, red blood cell count, hair quality, and melanin levels in a non-peer-reviewed study conducted among healthy men. Serum cholesterol was also reduced and seated-stature improved in this study.(30)
A statistically significant decrease in triglycerides and fasting blood glucose was observed in a double-blind, randomized controlled trial in 25 schizophrenic patients who took a total daily dose of 1,200 mg W. somnifera extract for 1 month versus those on placebo.(65)
An 8-week double-blind, randomized, placebo-controlled pilot study in 50 treatment-naive adults with subclinical hypothyroidism (elevated TSH) found that ashwagandha root extract (containing 5% withanolides) 300 mg twice daily significantly improved thyroid parameters. Serum T3 and T4 levels were significantly increased with ashwagandha over baseline and compared to placebo at 4 and 8 weeks, while serum TSH was significantly decreased. Treatment was well tolerated.(68)
Doses ranging from 125 to 12,000 mg/day have been used for anxiety(66): 300 mg twice daily of ashwagandha root extract for 10 weeks(77); and standardized ashwagandha extract dosed at 240 mg once daily for 60 days and 500 mg twice daily (titrated up on week 2 from 250 mg twice daily) for 12 weeks has been used.(72, 75)
Pregnancy / Lactation
Abortifacient properties have been reported for ashwagandha. Avoid use.61
In animal experiments, no fetal abnormalities were found in mice fed Withania root extract for 4 weeks. The progeny of experiment animals had a higher birth weight than those of controls.3 Because of the plant's antiangiogenic and cytotoxic properties, Withania should be avoided during pregnancy.
Case reports are lacking.3 Animal studies report potentiation of phenobarbital-induced sleep3 while interactions with some digoxin immunoassays have been demonstrated and are thought to be caused by similarity in chemical structure.62, 63
Limited clinical trials are available. Somnolence, loose stools/diarrhea, and stomach pain/abdominal pain have been more commonly reported with ashwagandha compared to placebo.(72) Safety of an 8-week course of ashwagandha 300 mg/day was established in healthy Indian adults in a double-blind, randomized, placebo-controlled study (N=80) with no significant differences noted between groups in adverse events or in hematological, liver function, alkaline phosphatase, or thyroid parameters.(78)
A Drug-induced Liver Injury (DILIN) prospective study reported data on liver injury related to consumption of ashwagandha supplements. Of the 5 cases, causality of ashwagandha was rated as definite in 1 case, highly likely in 2, probably in 1, and possible in 1. All cases were moderate in severity with no evidence of hepatic failure or impaired liver function. All patients presented with jaundice while other symptoms included nausea, abdominal pain, and/or pruritus.(60)
Subacute intraperitoneal toxicity studies at 100 mg/kg/day for 30 days led to decreased spleen, thymus, and adrenal weights, but no mortality or hematological changes were noted.64
A longer-term study (180 days) in rats at an oral dose of 100 mg/kg found no lethality, but did discover unfavorable increases in catecholamine content of the heart and decreases in the adrenal glands.17 At higher dosages (200 mg/kg/day), increases in lung and liver weight were observed.3, 4
In mice fed the extract of the entire plant as 25% of the total diet, microscopic lesions in the lung and liver were apparent, and vascular and tubular congestion were described.3
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