Health Care Professional Information

Scientific Name
Withania somnifera
Common Name

Ashwagandha, Indian ginseng, Winter cherry

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 increase energy and improve health and longevity (2), and topically as an analgesic (3). The active constituents include alkaloids, steroidal lactones, saponins, and withanolides.

In vitro studies suggest that ashwagandha has neuroprotective (26) (37) and anti-inflammatory properties which may protect against cartilage damage in osteoarthritis (4). In addition, improvements in hyperglycemia, hyperinsulinemia, and insulin sensitivity have been detected in an animal model of type 2 diabetes (5). Other studies indicate cytotoxic, chemopreventative, immunomodulating (8), and radiosensitizing effects (1) (9) (10), and enhancement in chromosomal stability (11).

Ashwagandha is rich in iron (2). Small-scale human studies suggest that it may promote growth in children and improve hemoglobin level and red blood cell count. Ashwagandha may also improve sexual performance in adults (2) and be useful in the treatment of male infertility (27). An herbal tea containing ashwagandha was shown to increase natural killer cell activity in healthy volunteers with recurrent coughs and colds (22). Data also indicate that ashwagandha may be helpful for anxiety (23), to affect markers of metabolic syndrome in schizophrenia patients receiving antipsychotic therapy,(34) and to improve cognitive function in patients with bipolar disorder (35). In another clinical trial, an herbomineral formula containing ashwagandha was shown to benefit osteoarthritis (13). Preliminary data suggest that ashwagandha may help to improve balance in patients with progressive degenerative cereberral ataxias (24).

Ashwagandha reduced the growth of breast, central nervous system, colon, and lung cancer cells (6) without affecting normal cells (7), but did not show any effectiveness against drug-resistant cancer stem cells (36). Withaferin A in ashwagandha enhanced oxaliplatin effects in human pancreatic cancer cells (38). Ashwagandha was also shown to prevent chemotherapy-induced neutropenia in mice (12).

In a small study of breast cancer patients, ashwagandha alleviated chemotherapy-induced fatigue and improved quality of life. Larger trials are needed to confirm these observations (31).

Purported Uses
  • Cancer treatment
  • Diabetes
  • Epilepsy
  • Fatigue
  • GI disorders
  • Pain
  • Rheumatoid arthritis
  • Sedation
  • Stress
Constituents
  • Alkanoids: isopelletierine, anaferine
  • Steroidal lactones: withanolides (withaferin-A, 12-deoxywithastramonolide, and withanolide-A), withaferins
  • Saponins: sitoindoside VII and VIII, Iron
    (2)
Mechanism of Action

Alkaloids, steroidal lactones, saponins, and withanolides are thought to be the biologically active components of ashwagandha. Studies have pointed to cyclooxygenase (COX) inhibition as the mechanism for the herb's anti-arthritic effects. In animal studies, Ashwagandha's anti-inflammatory activity was comparable to hydrocortisone (15). It exhibits antioxidant effects in the brain, and tranquilizing effects on the central nervous system in animals (2) possibly by influencing GABA receptor function (17).

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 increases cytotoxic T lymphocyte production (8). In vitro studies have shown that root extracts have cytotoxic properties against lung, colon, central nervous system, and breast cancer cell lines (6). Withaferin A induces 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 induces 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's cytotoxicity is related to its structure; it enhances ATPase and inhibits succinate dehydrogenase activities, impairing oxidative phosphorylation.

In animal studies, ashwagandha enhanced the effects of radiation therapy (20) by reducing tumor GSH levels (10). It was also shown to reverse paclitaxel-induced neutropenia in mice (12).

Warnings

Haemolytic anaemia and abdominal pain were reported following ingestion of ashwagandha/mucuna pills, later found to be contaminated (each pill contained 7.3 mg of lead and traces of arsenic, chromium and mercury) (32).

Contraindications

Pregnant women should avoid ashwagandha as it may induce abortion (14).

Adverse Reactions
  • Thyrotoxicosis was reported in a 32-year-old woman following ingestion of ashwagandha capsules for chronic fatigue. Her symptoms resolved after discontinuing ashwagandha (25).
  • A 28-year-old man experienced a burning and itching sensation, as well as discoloration of the skin/mucous membrane after taking ashwagandha for decreased libido. His symptoms abated with conventional treatment (33).
Herb-Drug Interactions
  • Triazolam: May potentiate the sedative effects of triazolam (30) .
Herb Lab Interactions

Ashwagandha may cause false elevation in digoxin immunoassay (28).
Ashwagandha may increase thyroxine levels (39).

Literature Summary and Critique

This study was conducted to determine the effect of naturopathic care on releiving anxiety. Eighty-one participants with moderate to severe anxiety lasting longer than 6 weeks were randomized to receive naturopathic care (NC) or standardized psychotherapy intervention (PT) for 12 weeks. The NC group received dietary counseling, deep breathing/relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera; 300 mg b.i.d. standardized to 1.5% with anolides, prepared from root). Those in the PT group received psychotherapy, and matched deep breathing/relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life, respectively. Researchers reported a significant reduction in the BAI scores in the NC group compared with those in PT group (P = .003). Significant differences were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life between groups with the NC group faring better. However, it is not clear if Ashwagandha alone would yield similiar benefit. Limitations of this study include small sample size, absence of a control group, and data based on patient-reported symptoms. Larger, well designed studies are warranted.

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References
  1. Prakash J, Gupta SK, Dinda AK. Withania somnifera root extract prevents DMBA-induced squamous cell carcinoma of skin in Swiss albino mice. Nutr Cancer. 2002;42(1):91-97.
  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.
  9. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.
  10. Devi PU. Withania somnifera Dunal (Ashwagandha): potential plant source of a promising drug for cancer chemotherapy and radiosensitization. Indian J Exp Biol. 1996;34(10):927-932.
  11. Panjamurthy K, Manoharan S, Menon VP, et al. Protective role of withaferin-A on 7,12-dimethylbenz(a)anthracene-induced genotoxicity in bone marrow of Syrian golden hamsters. J Biochem Mol Toxicol. 2008;22(4):251-258.
  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.
  14. Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy (OR): Eclectic Medical Publications; 2001.
  15. al-Hindawi MK, al-Khafaji SH, Abdul-Nabi MH. Anti-granuloma activity of Iraqi Withania somnifera. J Ethnopharmacol. 1992;37(2):113-116.
  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.
  20. Devi PU, Sharada AC, Solomon FE. In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma. Cancer Lett. 1995;95(1-2):189-193.
  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.
  22. Bhat J, Damle A, Vaishnav PP, et al. In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs. Phytother Res. 24(1):129-35.
  23. Cooley K, Szczurko O, Perri D, et al. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One. 2009;4(8):e6628.
  24. Sriranjini SJ, Pal PK, Devidas KV, Ganpathy S. Improvement of balance in progressive degenerative cerebellar ataxias after Ayurvedic therapy: A preliminary report. Neurol India. 2009;57(2):166-71.
  25. van der Hooft CS, Hoekstra A, Winter A, et al. [Thyrotoxicosis following the use of ashwagandha]. Ned Tijdschr Geneeskd. 2005;149(47):2637-8.
  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.
  29. Grover A, Singh R, Shandilya A, et al.Ashwagandha derived withanone targets TPX2-Aurora a complex: Computational and experimental evidence to its anticancer activity. PLoS ONE. 2012;7(1).
  30. Kumar A, Kulkarni SK. Effect of herbals on sleep and their interactions with hypnotic drugs. Indian J Pharm Sci. 2005;67(3):391-393.
  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.

Consumer Information

How It Works

Bottom Line: Ashwagandha slows down the growth of cancer cells in laboratory tests and enhances radiation therapy in animals, but anticancer effects have not been demonstrated in humans.

Ashwagandha is a popular Ayurvedic herb. Studies show that it has anti-inflammatory effects. Ashwagandha also relaxes the central nervous system in animals. Laboratory studies found that ashwagandha kills some cancer cells and enhances some immune cells possibly by damaging the cancer cells' ability to generate the energy it needs to reproduce. Ashwagandha also reduces the level of an important antioxidant in tumor cells, which may enhance the ability of radiation therapy to kill those cells. However, this herb may induce abortion, so pregnant women should not use it.

Purported Uses
  • To treat cancer
    Ashwagandha has shown promise in animal and laboratory experiments, but studies in humans are needed to support its use in cancer treatment.
  • To treat diabetes
    Studies in laboratory animals suggest that ashwagandha may improve type 2 diabetes.
  • To treat epilepsy
    There are no data to support this claim.
  • To reduce fatigue
    Ashwagandha has been shown to increase blood cell counts in the lab; however, it is unclear if this will reduce fatigue in humans.
  • To treat digestive disorders
    No scientific evidence supports this use.
  • To reduce pain
    Ashwagandha has been shown to have a tranquilizing effect in animals, but human studies are needed.
  • To treat rheumatoid arthritis
    A clinical trial showed that a compound of herbs and minerals containing ashwagandha reduced the pain of rheumatoid arthritis. Because the formula contained multiple herbs and minerals, whether ashwagandha played a role in the reduction in pain severity and disability is unclear.
  • As a sedative
    Ashwagandha has been shown to have a tranquilizing effect in animal studies.
Research Evidence

Anxiety:
This study was done to find out the effect of naturopathic care on releiving anxiety. Eighty-one participants with moderate to severe anxiety lasting longer than 6 weeks  received either naturopathic care (NC) or standardized psychotherapy intervention (PT) for 12 weeks. The NC group received dietary counseling, deep breathing/relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha. Those in the PT group received psychotherapy, and matched deep breathing/relaxation techniques, and placebo pills. Patients in the NC group fared much better than those in the PT group with respect to anxiety and overall quality of life, but it is not clear if ashwagandha alone would have similar benefits.

Patient Warnings

Hemolytic anaemia and abdominal pain were reported following ingestion of ashwagandha/mucuna pills, later found to be contaminated (each pill contained 7.3 mg of lead and traces of arsenic, chromium and mercury).

Do Not Take If
  • You are pregnant: Ashwagandha may induce abortion.
  • You are taking sedatives: Ashwagandha may increase sedative effects.
Side Effects
  • Hyperthyroidism was reported in a 32-year-old woman following ingestion of ashwagandha capsules for chronic fatigue. Her symptoms resolved after discontinuing ashwagandha.
  • A 28-year-old man experienced a burning and itching sensation, as well as discoloration of the skin/mucous membrane after taking ashwagandha for decreased libido. His symptoms abated with conventional treatment.
Special Point

Ashwagandha may affect certain lab tests that measure thyroid functioning or measure digoxin levels.

E-mail your questions and comments to aboutherbs@mskcc.org.