Ashwagandha

Purported Benefits, Side Effects & More
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Ashwagandha

Purported Benefits, Side Effects & More
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Ashwagandha -- Potential Benefits, Side Effects and More

Common Names

  • Ashwagandha
  • Indian ginseng
  • Winter cherry

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Ashwagandha is a popular herb used in traditional Indian medicine (Ayurveda) for stress relief and to improve general health. It can help you relax and reduce swelling.

Some lab studies show that it can slow the growth of cancer cells, but this effect has not been observed in humans.

What are the potential uses and benefits?

Ashwagandha is used:

  • To reduce anxiety (strong feelings of worry)
  • To reduce stress
  • To reduce fatigue (feeling more tired or weak than usual)
  • To reduce joint pain
  • To treat diabetes

It’s generally safe to use ashwagandha in food and tea. However, talk with your healthcare providers before taking supplements or higher amounts of ashwagandha. Supplements are stronger than the herbs you would use in cooking.

Ashwagandha can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of using ashwagandha may include:

  • Nausea (feeling like you’re going to throw up)
  • Headache
  • Drowsiness
  • Stomach irritation
  • Diarrhea (loose or watery stool)
What else do I need to know?
  • Don’t use ashwagandha if you’re pregnant because it may cause abortion (end your pregnancy).
  • Talk with your doctor if you have hormone-sensitive prostate cancer because ashwagandha may increase testosterone levels. This can interfere with your treatments.
  • Ashwagandha may increase the drowsiness effects of some prescription medications so talk with your healthcare provider before taking it.
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For Healthcare Professionals

Scientific Name
Withania somnifera
Clinical Summary

A popular Ayurvedic herb, ashwagandha is often used in formulations prescribed for stress, strain, fatigue, pain, skin diseases, diabetes, gastrointestinal disease, rheumatoid arthritis, and epilepsy (1). It is also used as a general tonic to improve energy levels, health, and longevity (2), and topically as an analgesic (3). Active constituents include alkaloids, steroidal lactones, saponins, and withanolides.

Preclinical studies showed neuroprotective (26) (37) and anti-inflammatory properties that may protect against cartilage damage in osteoarthritis (4), and improvements in hyperglycemia, hyperinsulinemia, and insulin sensitivity in a murine model of type 2 diabetes (5). Additional studies found cytotoxic, immunomodulating (8), chemopreventive (1) and radiosensitizing effects (10), and enhancement in chromosomal stability (11).

Limited clinical data suggest ashwagandha promotes growth, hemoglobin level, and red blood cell count in children (2), improves sexual health (2) (61), male infertility (27), and relieves mild to moderate climacteric symptoms in perimenopausal women (59).  It may also help relieve constipation (69), lower fatigue (70), anxiety (23) (54) and stress (52) (62) (63) (71) with a systematic review/dose-response meta-analysis citing the need for high-quality evidence (64). Improvements were also seen in both non-restorative sleep in healthy adults (55) and sleep quality in patients with insomnia (51) (56). In patients with schizophrenia, adjunctive use improved symptoms and stress (43) (50), and affected markers of metabolic syndrome (34). Preliminary findings indicate improvements in measures of cognitive function in patients with bipolar disorder (35) and balance in patients with progressive degenerative cerebral ataxias (24). Ashwagandha formulations may also benefit patients with osteoarthritis (13),  rheumatoid arthritis (72), exerting analgesic, anti-inflammatory, and chondro-protective effects in those with knee joint pain (41).

Ashwagandha exerted anticancer effects against several cancer cell lines (6) (7), but was ineffective against drug-resistant cancer stem cells (36). It prevented chemo-induced neutropenia in a murine model (12), and the compound Withaferin A enhanced oxaliplatin effects in human pancreatic cancer cells (38). A small trial of breast cancer patients reported reduced chemo-induced fatigue and improved quality of life (31). Confirmatory research is needed.

Ashwagandha may increase testosterone levels and therefore, patients with hormone-sensitive prostate cancer should consult their physicians before taking it (48).

Purported Uses and Benefits
  • Anxiety
  • Stress
  • Fatigue
  • Rheumatoid arthritis
  • Diabetes
Mechanism of Action

Alkaloids, steroidal lactones, saponins, and withanolides are considered the biologically active components of ashwagandha. Anti-arthritic effects are attributed to cyclooxygenase (COX) inhibition.

In animal studies, anti-inflammatory activity by ashwagandha was comparable to hydrocortisone (15). Brain antioxidant effects and CNS tranquilizing effects may be due to influences on GABA receptor function (2) (17). Withanolides in the roots and leaves are considered similar to steroids in their biological activities (41). Triethylene glycol, a compound isolated from the leaves, was identified as an active sleep-inducing component in a murine model, and may potentially be used to relieve insomnia (42).

Microarray analysis revealed that ashwagandha represses proinflammatory gene expression, including IL-6, IL-1β, IL-8, Hsp70, and STAT-2, and induces p38/MAPK expression in a prostate cancer cell line (16). Ashwagandha may inhibit tumor growth (1) (21) and increased cytotoxic T lymphocyte production (8). In vitro studies show that root extracts have cytotoxic properties against lung, colon, CNS, and breast cancer cell lines (6). Withaferin A induced reactive oxygen species (ROS) generation and disruption of mitochondrial function in a human leukemia cell line, thereby inducing apoptosis (18). In estrogen receptor-positive (ER+) and negative (ER-) breast cancer cells, withaferin A induced apoptosis and decreased tumor size (19). Apoptosis of cancer cells by withanone is mediated through p53 (7). Withianone also exerts anticancer activity by binding to the TPX2-Aurora A Complex (29). Other studies show ashwagandha cytotoxicity is related to its structure. It enhances ATPase and inhibits succinate dehydrogenase activities, impairing oxidative phosphorylation.

In animal studies, ashwagandha enhanced radiation therapy effects (20) by reducing tumor GSH levels (10), and reversed paclitaxel-induced neutropenia in mice (12). No significant interactions have been reported between ashwagandha and either CYP3A4 or CYP2D6 enzymes in human liver microsomes (40).

Warnings
  • Hemolytic anemia and abdominal pain were reported following ingestion of ashwagandha/mucuna pills containing high amounts of lead (32). Symptoms resolved following standard treatment.
Contraindications
  • Ashwagandha may increase testosterone levels, and should therefore be avoided in patients with hormone-sensitive prostate cancer (48).
  • Patients who take benzodiazepines, anticonvulsants, or barbiturates should likely avoid ashwagandha because this botanical may have both sedative and GABAnergic effects (49).
  • Pregnant women should avoid ashwagandha as it may induce abortion at higher doses (49).
Adverse Reactions

Commonly reported effects: Mild to moderate and transient drowsiness, upper GI discomfort, loose stools (43) (53)

Less common effects reported: Giddiness, drowsiness, hallucinogenic, vertigo, nasal congestion (rhinitis), cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash and weight gain (53)

Case reports

  • Nausea, headache, and gastritis: Reported in a clinical study, but symptoms were managed by standard therapies (41)
  • Thyrotoxicosis: Associated with ingestion of ashwagandha supplements for chronic fatigue (25), hypothyroidism (65) and insomnia (73). Symptoms resolved in all cases after cessation of supplement use.
  • Burning, itching, and discoloration of skin/mucous membrane: In a 28-year-old man after taking ashwagandha for decreased libido. Symptoms abated with conventional treatment (33).
  • Ventricular tachycardia: 2 cases were possibly associated with the use of herbomineral preparations that contained ashwagandha (45).
  • Elevation of liver enzymes, skin rash, fatigue, fever, edema, and diarrhea: In patients with advanced stage high-grade osteosarcoma, following administration of Withaferin-A (47).
  • Kidney transplant rejection: In a 69-year-old patient associated with use of ashwagandha. The patient needed a graft nephrectomy and was continued on maintenance dialysis (57).
  • Liver injury: Associated with use of ashwagandha supplements. Symptoms improved after discontinuing ashwagandha with some patients needing additional treatments (60) (66) (67) (74) (75).
  • Acute steatohepatitis: In a 43-year-old female with a past medical history of iron deficiency anemia after taking multiple supplements which included ashwagandha, in addition to alcohol and ibuprofen (68).
  • Reversible cerebral vasoconstriction syndrome: In a 47-year-old female with a history of ashwagandha, medical marijuana, and serotonin-norepinephrine reuptake inhibitor (SNRIs) use. Her symptoms resolved with conventional treatment (76).
Herb-Drug Interactions
  • Anticonvulsants, barbiturates, and benzodiazepines: Preclinical studies suggest that ashwagandha has sedative and GABAnergic properties, and may have additive effects (30) (49). Clinical relevance has yet to be determined.
  • Cytochrome P450 2B6 substrates: Ashwagandha inhibited CYP2B6 in vitro, and may affect the intracellular concentration of drugs metabolized by this enzyme (58). Clinical relevance is yet to be determined.
  • Cytochrome P450 3A4 substrates: Ashwagandha was found to be a moderate inducer of CYP3A4 in vitro, and can affect the intracellular levels of drugs metabolized by this enzyme (58). Clinical relevance is not known.
Herb Lab Interactions
  • May cause false elevation in digoxin immunoassay (28).
  • May increase thyroxine levels (39).
Dosage (OneMSK Only)
References
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  2. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334-346.
  3. Dafni A, Yaniv Z. Solanaceae as medicinal plants in Israel. J Ethnopharmacol. 1994;44(1):11-18.
  4. Sumantran VN, Chandwaskar R, Joshi AK, et al. The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. Phytother Res. 2008;22(10):1342-1348.
  5. Anwer T, Sharma M, Pillai KK, et al. Effect of Withania somnifera on insulin sensitivity in non-insulin-dependent diabetes mellitus rats. Basic Clin Pharmacol Toxicol. 2008;102(6):498-503.
  6. Jayaprakasam B, Zhang Y, Seeram NP, et al. Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves. Life Sci. 2003;74(1):125-132.
  7. Widodo N, Kaur K, Shrestha BG, et al. Selective killing of cancer cells by leaf extract of ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect. Clin Cancer Res. 2007;13(7):2298-2306.
  8. Davis L, Kuttan G. Effect of Withania somnifera on CTL activity. J Exp Clin Cancer Res. 2002;21(1):115-118.
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  12. Gupta YK, Sharma SS, Rai K, et al. Reversal of paclitaxel induced neutropenia by Withania somnifera in mice. Indian J Physiol Pharmacol. Apr 2001;45(2):253-257.
  13. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991;33(1-2):91-95.
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  16. Aalinkeel R, Hu Z, Nair BB, et al. Genomic analysis highlights the role of the JAK-STAT signaling in the anti-proliferative effects of dietary flavonoid -’Ashwagandha’ in prostate cancer cells. Evid Based Complement Alternat Med. 2010 Jun;7(2):177-87.
  17. Kulkarni SK, Akula KK, Dhir A. Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system. Indian J Exp Biol. 2008;46(6):465-469.
  18. Malik F, Kumar A, Bhushan S, et al. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine. Apoptosis. 2007;12(11):2115-2133.
  19. Stan SD, Hahm ER, Warin R, et al. Withaferin A causes FOXO3a- and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo. Cancer Res. 2008;68(18):7661-7669.
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  21. Devi PU, Sharada AC, Solomon FE. Antitumor and radiosensitizing effects of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma-180. Indian J Exp Biol. 1993;31(7):607-611.
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  26. Kumar S, Harris RJ, Seal CJ, Okello EJ. An aqueous extract of Withania somnifera root inhibits amyloid β fibril formation in vitro. Phytother Res. 2012;26(1):113-7.
  27. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010;94(3):989-96.
  28. Dasgupta A, Tso G, Wells A. Effect of Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha on serum digoxin measurement by digoxin III, a new digoxin immunoassay. J Clin Lab Anal. 2008;22(4):295-301.
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  31. Biswal BM, Sulaiman SA, Ismail HC, Zakaria H, Musa KI. Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy-induced fatigue and quality of life in breast cancer patients. Integr Cancer Ther. 2013;12(4):312-22.
  32. Toniolo M, Ceschi A, Meli M, Lohri A, Favre G. Haemolytic anaemia and abdominal pain—a cause not to be missed. Br J Clin Pharmacol. 2011;72(1):168-9.
  33. Sehgal VN, Verma P, Bhattacharya SN. Fixed-drug eruption caused by ashwagandha (Withania somnifera): a widely used Ayurvedic drug. Skinmed. 2012;10(1):48-9.
  34. Agnihotri AP, Sontakke SD, Thawani VR, Saoji A, Goswami VS. Effects of Withania somnifera in patients of schizophrenia: A randomized, double blind, placebo controlled pilot trial study. Indian J Pharmacol. 2013;45:417-418.
  35. Chengappa KN, Bowie CR, Schlicht PJ, Fleet D, Brar JS, Jindal R. Randomized placebo-controlled adjunctive study of an extract of Withania somnifera for cognitive dysfunction in bipolar disorder. J Clin Psychiatry. 2013;74:1076-1083.
  36. Maliyakkal N, Appadath Beeran A, Balaji SA, Udupa N, Ranganath Pai S, Rangarajan A. Effects of Withania somnifera and Tinospora cordifolia extracts on the side population phenotype of human epithelial cancer cells: Toward targeting multidrug resistance in cancer. Integr Cancer Ther. 2015;14:156-171.
  37. Shah N, Singh R, Sarangi U, et al. Combinations of ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. PLoS One. 2015;10:e0120554.
  38. Li X, Zhu F, Jiang J, et al. Synergistic antitumor activity of withaferin a combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3k/Akt pathway in human pancreatic cancer cells. Cancer Lett. 2015;357:219-230.
  39. Gannon JM, Forrest PE, Roy Chengappa KN. Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder. J Ayurveda Integr Med. 2014;5:241-245.
  40. Savai J, Varghese A, Pandita N, et al. Investigation of CYP3A4 and CYP2D6 interactions of Withania somnifera and Centella asiatica in human liver microsomes. Phytother Res. May 2015;29(5):785-790.
  41. Ramakanth GS, Uday Kumar C, Kishan PV, et al. A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain. J Ayurveda Integr Med. Jul - Sep 2016;7(3):151-157.
  42. Kaushik MK, Kaul SC, Wadhwa R, Yanagisawa M, Urade Y. Triethylene glycol, an active component of Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction. PLoS One. 2017 Feb 16;12(2):e0172508.
  43. Chengappa KNR, Brar JS, Gannon JM, et al. Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. Jul 10 2018;79(5).
  44. Deshpande A, Irani N, Balakrishnan R. Study protocol and rationale for a prospective, randomized, double-blind, placebo-controlled study to evaluate the effects of Ashwagandha (Withania somnifera) extract on nonrestorative sleep. Medicine (Baltimore). Jun 2018;97(26):e11299.
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  51. 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 Sep 28;11(9):e5797.
  52. Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019 Sep;98(37):e17186.
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  58. Kumar S, Bouic PJ, Rosenkranz B. Investigation of CYP2B6, 3A4 and β-esterase interactions of Withania somnifera (L.) dunal in human liver microsomes and HepG2 cells. J Ethnopharmacol. 2021 Apr 24;270:113766.
  59. Gopal S, Ajgaonkar A, Kanchi P, et al. Effect of an ashwagandha (Withania Somnifera) root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study. J Obstet Gynaecol Res. 2021 Dec;47(12):4414-4425.
  60. Ireland PJ, Hardy T, Burt AD, Donnelly MC. Drug-induced hepatocellular injury due to herbal supplement ashwagandha. J R Coll Physicians Edinb. 2021 Dec;51(4):363-365.
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  64. Akhgarjand C, Asoudeh F, Bagheri A, et al. Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2022 Nov;36(11):4115-4124.
  65. Kamal HI, Patel K, Brdak A, Heffernan J, Ahmad N. Ashwagandha as a Unique Cause of Thyrotoxicosis Presenting With Supraventricular Tachycardia. Cureus. 2022 Mar 25;14(3):e23494.
  66. Lubarska M, Hałasiński P, Hryhorowicz S, et al. Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. Int J Environ Res Public Health. 2023 Feb 22;20(5):3921.
  67. Tóth M, Benedek AE, Longerich T, Seitz HK. Ashwagandha-induced acute liver injury: A case report. Clin Case Rep. 2023 Mar 14;11(3):e7078
  68. Pusec CM, Wolsky R, Llerena C, Sura P. A Case of Supplement-Induced Hepatitis. Cureus. 2022 Oct 18;14(10):e30433.
  69. Punukollu RS, Chadalawada AK, Siddabattuni K, Gogineni NT. A blend of Withania somnifera (L.) Dunal root and Abelmoschus esculentus (L.) Moench fruit extracts relieves constipation and improves bowel function: A proof-of-concept clinical investigation.  J Ethnopharmacol. 2024 Jan 10;318(Pt B):116997.
  70. Smith SJ, Lopresti AL, Fairchild TJ. Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial.  J Psychopharmacol. 2023 Nov;37(11):1091-1104. 
  71. Della Porta M, Maier JA, Cazzola R. Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review.  Nutrients. 2023 Dec 5;15(24):5015.
  72. Ansari UAMA, Uddin Q, Husain N, Ahmad T, Fatima SH, Minhajuddin A. Evaluation of the efficacy and safety of a herbal formulation for rheumatoid arthritis - A non-inferiority randomized controlled trial.  J Ethnopharmacol. 2024 May 10;325:117833.
  73. Hayashi M, Hamada H, Azuma SI, Hayashi K. Painless Thyroiditis by Withania somnifera (Ashwagandha).  Cureus. 2024 Mar 1;16(3):e55352. 
  74. Vazirani S, Kothari A, Fujimoto J, Gomez M. Supplements Are Not a Synonym for Safe: Suspected Liver Injury From Ashwagandha.  Fed Pract. 2023 Sep;40(9):315-319.
  75. Bokan G, Glamočanin T, Mavija Z, et al. Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause.  Pharmaceuticals (Basel). 2023 Aug 10;16(8):1129. 
  76. Patel PA, Sanborn E, Then R, Williams DM. Recurrent Reversible Cerebral Vasoconstriction Syndrome: A Report of Two Cases.  Cureus. 2023 Aug 5;15(8):e42992. 
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