Ashwagandha

Plant Part Used

Root

Active Constituents

Alkaloids (tropane-type), steroidal lactones (withanolides, withaferins), saponins. (1)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Ashwagandha root, also known as winter cherry or Indian ginseng, is an important herb from the Ayurvedic or Indian system of medicine. Ashwagandha has been traditionally used for the treatment of debility, emaciation, impotence, and premature aging. (2) This dietary supplement is used to enhance mental and physical performance, improve learning ability, and decrease stress and fatigue. (3) Ashwagandha is a general tonic to be used in stressful situations, especially insomnia, overwork, nervousness, and restlessness.

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

450mg (standardized extract), 2-3 times a day.

Most Common Dosage

450mg (standardized extract), 2 times a day.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to at least 1.5% withanolides per dose.

Uses

Frequently Reported Uses

  • Adaptogen, Tonic
  • Exhaustion
  • Stress
  • Convalescence After Acute Or Chronic Illness
  • Anti-Aging
  • Arthritis, Inflammation
  • Adjunctive Support In Chemotherapy And Radiation
  • Nervous Exhaustion
  • Radiation Therapy
Other Reported Uses
  • Antioxidant
  • Anemia
  • Opiate Addiction
  • Poor Appetite
  • Impotence
  • Sedative
  • Weight Gain

Toxicities & Precautions

General

Ashwagandha has been reported safe in recommended dosages. (4)

Health Conditions

Based on pharmacology, do not use in individuals with hyperthyroidism; ashwagandha has been reported in an animal study to increase T4 activity and subsequently thyroid function. (5)

Pregnancy/ Breast Feeding

Based on pharmacology, do not use in pregnancy due to potential abortifacient effects. (6)

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Studies have indicated that ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. (7) It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood.

Ashwagandha is an adaptogen, or substance that helps protect the body against various emotional, physical, and environmental stresses. (8) Ashwagandha is reported to have tonic or adaptogenic effects similar to the panax ginsengs. (9) In one study, the levels of corticosterone in the adrenal glands of stressed (5 h constant swimming) male albino mice treated with ashwagandha and panax ginseng preparations and compared with non-treated stressed and normal controls. (10) The herbal therapies increased the corticosterone levels in all the groups. However, the physical endurance (increased survival time) of swimming mice in this study was not affected by ashwagandha administration (500mg/kg p.o.). Another recent laboratory animal study did report that ashwagandha increased swimming time in rats during a swimming endurance test, with a significant increase in relative heart weight and glycogen content in myocardium and liver in the treated group. (11) Additional studies have supported antistress, neuroprotective effects findings in ashwagandha (12) as well as antianxiety characteristics. (13)

Ashwagandha is also reported to have immunostimulatory activity, because treatment was accompanied by significant increases in hemolytic antibody responses towards human erythrocytes. Ashwagandha reportedly prevented myelosuppression in mice treated with three immunosuppressive drugs with a significant increase in hemoglobin concentration. (14) Another recent laboratory animal study reported that ashwagandha administration stimulated immunological activity in Babl/c mice. Treatment with five doses of Withania root extract (20 mg/dose/animal; intraperitoneal) was found to enhance the total WBC count on day 10. Bone marrow cellularity as well as alpha-esterase positive cell number also increased significantly after the administration of the extract. (15)

Ashwagandha is rich in iron, which would increase hemoglobin and red blood cell count in treated individuals. (16) This agent should be used in moderation in men with known cardiovascular risk because iron may potentially accelerate this risk. Ashwagandha is anabolic, containing substantial amounts of the amino acids arginine and ornithine. These amino acids are needed for proper nervous system function. (17) Ashwagandha was reported to increase the sexual performance in 71 percent of men involved in a study with the herb. (18) Also, ashwagandha has been reported to be useful in opiate withdrawal and addiction treatment. (19)

Ashwagandha has been studied for possible tumor inhibitory effects, as well as a radiosensitizer when administered with radiation therapy. (20) , (21) The gentle application of heat has been reported to enhance the radiosensitizing effects of ashwagandha. (22) A recent laboratory animal study reported that ashwagandha extract administration (20mg/dose/animal given intraperitoneal) was found to inhibit 20-methylcholanthrene induced sarcoma development in mice and increase the life span of tumor bearing animals. (23) Another animal study reported that administration of an ashwagandha extract enhanced the levels of Interferon gamma (IFN-gamma), Interleukin-2 (IL-2) and granulocyte macrophage colony stimulating factor (GM-CSF) in mice. (24) The lowered levels of IFN gamma, IL-2 and GM-CSF after treatment with cyclophosphamide was reversed by the administration of ashwagandha. The ashwagandha extract also lowered the levels of tumour necrosis factor alpha (TNF-alpha) production. Administration of bone marrow cells from donor mice treated with ashwagandha extract increased the spleen nodular colonies in irradiated mice compared to those treated with normal bone marrow cells. The number of nodular colonies increased significantly when these animals continued with ashwagandha extract treatment. The authors concluded that the immunopotentiating and myeloprotective effect of ashwagandha was potentially due to the enhancement of cytokine production and stem cell proliferation and its differentiation.

Another animal study reported on the immunomodulatory activities of ashwagandha in immune inflammation. (25) Cyclophosphamide-induced potentiation of delayed-type hypersensitivity reaction was suppressed in animals treated with an extract of ashwagandha, with a significant increase in white blood cell counts and platelet counts being observed in the extract treated animals. A protective effect in cyclophosphamide-induced myelosuppression was observed in animals treated with ashwagandha, revealing a significant increase in white blood cell counts and platelet counts. Cyclophosphamide-induced immunosuppression was counteracted by treatment with the herbal extract, revealing a significant increase in hemagglutinating antibody responses and hemolytic antibody responses towards sheep red blood cells.

Ashwagandha has also been reported to protect against cyclophosphamide induced toxicity. (26) , (27) A rat study indicated that ashwagandha may be a protective agent for the liver and kidney damage that can be induced by carbendazim, a fungicide. (28) Ashwagandha has been used in the treatment of arthritis and other inflammatory conditions. (29) , (30) Ashwagandha is a potent antioxidant, inhibiting lipid peroxidation and increasing enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). (31) , (32) In one animal study, an aqueous suspension of the root extract of ashwagandha was evaluated for its effect on lipid peroxidation in stress-induced animals. (33) Simultaneous oral administration of ashwagandha (100 mg/kg) prevented the rise in lipid peroxidase in rabbits and mice. The antioxidant effect of active components of ashwagandha may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, anti-inflammatory, and anti-aging effects produced in experimental animals and in clinical studies. (34)

Another animal study reported the effectiveness of ashwagandha given orally once daily for 7 consecutive days in a dose of 100 mg/kg infection of Aspergillus fumigatus prolonged the survival period of infected mice. (35) This protective activity was probably related to the observed increases in phagocytosis and intracellular killing of peritoneal macrophages induced by ashwaganda treatment. The authors report that the probable mechanism underlying the protective action of ashwagandha against systemic Aspergillus infection was in relation to its potential to activate the macrophage function.

Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Constituents isolated from an aqueous methanol extract from the roots of cultivated varieties of ashwagandha have reported acetylcholinesterase activity. (36) The data suggest ashwagandha may affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from ashwaganda observed in animals and humans.

A human study of 6 individuals with mild NIDDM and six mild hypercholesterolemic subjects were treated with the powder of roots of ashwagandha for 30 days. (37) A decrease in blood glucose was comparable to that of an oral hypoglycemic drug. Significant increases in urine sodium, urine volume, significant decrease in serum cholesterol, triglycerides, LDL and VLDL cholesterol were observed indicating that root of ashwagandha is a potential source of hypoglycemic, diuretic and hypocholesterolemic agents.

Of interest is a recent report that ashwagandha administration in laboratory animals may stimulate thyroid function by enhancing serum T4 concentration. (38) The authors report also that the ashwagandha plant extract showed an increase in hepatic glucose-6-phosphatase (G-6-Pase) activity and anti-peroxidative effects, as indicated either by a decrease in hepatic lipid peroxidation and/or by an increase in the activity of antioxidant enzyme(s).

References

  1. Sudhir S, et al. Pharmacological Studies on Leaves of Withania somnifera. Planta Med. Feb1986;1:61-63.
  2. Boone K. Withania – The Indian Ginseng and Anti-aging Adaptogen. Nutrition and Healing. Jun1998;5(6):5-7.
  3. View Abstract: Singh A, Naidu PS, Gupta S, Kulkarni SK. Effect of natural and synthetic antioxidants in a mouse model of chronic fatigue syndrome. J Med Food. Dec2002;5(4):211-20.
  4. Boone K. Withania – The Indian Ginseng and Anti-aging Adaptogen. Nutrition and Healing. Jun1998;5(6):5-7.
  5. View Abstract: Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the Regulation of Circulating Thyroid Hormone Concentrations in Female Mice. J Ethnopharmacol. Nov1999;67(2):233-9.
  6. Sudhir S, et al. Pharmacological Studies on Leaves of Withania somnifera. Planta Med. Feb1986;1:61-63.
  7. View Abstract: Mishra LC, Singh BB, Dagenais S. Scientific Basis for the Therapeutic Use of Withania somnifera (Ashwagandha): A Review. Altern Med Rev. Aug2000;5(4):334-46.
  8. View Abstract: Archana R, Namasivayam A. Antistressor Effect of Withania somnifera. J Ethnopharmacol. Jan1999;64(1):91-3.
  9. View Abstract: Grandhi A, et al. A Comparative Pharmacological Investigation of Ashwagandha and Ginseng. J Ethnopharmaco. Dec1994;44(3):131-35.
  10. View Abstract: Singh A, Saxena E, Bhutani KK. Adrenocorticosterone Alterations in Male, Albino Mice Treated with Trichopus zeylanicus, Withania somnifera and Panax ginseng Preparations. Phytother Res. Mar2000;14(2):122-5.
  11. View Abstract: Dhuley JN. Adaptogenic and Cardioprotective Action of Ashwagandha in Rats and Frogs. J Ethnopharmacol. Apr2000;70(1):57-63.
  12. View Abstract: Jain S, Shukla SD, Sharma K, Bhatnagar M. Neuroprotective Effects of Withania somnifera Dunn. in Hippocampal Sub-regions of Female Albino Rat. Phytother Res. Sep2001;15(6):544-8.
  13. View Abstract: Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. Dec2000;7(6):463-9.
  14. View Abstract: Ziauddin M, et al. Studies on the Immunomodulatory Effects of Ashwagandha. J Ethnopharmacol. Feb1996;50(2):69-76.
  15. View Abstract: Davis L, Kuttan G. Immunomodulatory Activity of Withania somnifera. J Ethnopharmacol. Jul2000;71(1-2):193-200.
  16. Boone K. Withania – The Indian Ginseng and Anti-aging Adaptogen. Nutrition and Healing. Jun1998;5(6):5-7.
  17. View Abstract: Elsakka M, et al. New Data Referring to Chemistry of Withania Somnifera Species. Rev Med Chir Soc Med Nat Lasi. Apr1990;94(2):385-87.
  18. Boone K. Withania – The Indian Ginseng and Anti-aging Adaptogen. Nutrition and Healing. Jun1998; 5(6): 5-7.
  19. View Abstract: Kulkarni SK, et al. Inhibition of Morphine Tolerance and Dependence by Withania Somnifera in Mice. J Ethnopharmacol. Aug1997;57(3):213-17.
  20. View Abstract: Kuttan G. Use of Withania Somnifera Dunal as an Adjuvant during Radiation Therapy. Indian J Exp Biol. Sept1996;34(9):854-56.
  21. View Abstract: Sharad AC, et al. Antitumor and Radiosensitizing Effects of Withaferin A on Mouse Ehrlich Ascites Carcinoma In Vivo. Acta Oncol. 1996;35(1):95-100.
  22. View Abstract: Devi PU, et al. Withaferin A: A New Radiosensitizer From the Indian Medicinal Plant Withania Somnifera. Int J Radiat Biol. Feb1996;69(2):193-97.
  23. View Abstract: Davis L, Kuttan G. Effect of Withania somnifera on 20-methylcholanthrene Induced Fibrosarcoma. J Exp Clin Cancer Res. Jun2000;19(2):165-7.
  24. View Abstract: Davis L, Kuttan G. Effect of Withania somnifera on Cytokine Production in Normal and Cyclophosphamide Treated Mice. Immunopharmacol Immunotoxicol. Nov1999;21(4):695-703.
  25. View Abstract: Agarwal R, Diwanay S, Patki P, et al. Studies on Immunomodulatory Activity of Withania somnifera (Ashwagandha) Extracts in Experimental Immune Inflammation. J Ethnopharmacol. Oct1999;67(1):27-35.
  26. View Abstract: Davis L. Kuttan G. Suppressive Effect of Cyclophosphamide-induced Toxicity by Withania somnifera Extract in Mice. J Ethnopharmacol. Oct1998;62(3):209-14.
  27. View Abstract: Praveenkumar V, et al. Chemoprotective Action of Rasayanas against Cyclosphamide Toxicity. Tumori. Aug1994;80(4):306-08.
  28. View Abstract: Akbarsha MA, Vijendrakumar S, Kadalmani B, Girija R, Faridha A. Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat. Phytomedicine. Dec2000;7(6):499-507.
  29. Begum VH, et al. Long Term Effect of Herbal Drug Withania Somnifera on Adjuvant Induced Arthritis in Rats. Indian J Exp Biol. Nov1988;26(11):877-82.
  30. Anbalagan K, et al. Influence of An Indian Medicine (Ashwagandha) on Acute-Phase Reactants in Inflammation. Indian J Exp Biol. Mar1981;19(3):245-49.
  31. View Abstract: Bhattacharya SK, et al. Antioxidant Activity of Glycowithanolides from Withania Somnifera. Indian J Exp Biol. Mar1997;35(3):236-39.
  32. View Abstract: Bhattacharya A, Ghosal S, Bhattacharya SK. Anti-oxidant Effect of Withania somnifera Glycowithanolides in Chronic Footshock Stress-induced Perturbations of Oxidative Free Radical Scavenging Enzymes and Lipid Peroxidation in Rat Frontal Cortex and Striatum. J Ethnopharmacol. Jan2001;74(1):1-6.
  33. View Abstract: Dhuley JN. Effect of Ashwagandha on Lipid Peroxidation in Stress-Induced Animals. J Ethnopharmacol. Mar1998;60(2):173-78.
  34. View Abstract: Dhuley JN. Effect of Ashwagandha on Lipid Peroxidation in Stress-Induced Animals. J Ethnopharmacol. Mar1998;60(2):173-78.
  35. View Abstract: Dhuley JN. Therapeutic Efficacy of Ashwagandha Against Experimental Aspergillosis in Mice. Immunopharmacol Immunotoxicol. Feb1998;20(1):191-8.
  36. View Abstract: Schliebs R, Liebmann A, Bhattacharya SK, et al. Systemic Administration of Defined Extracts from Withania somnifera (Indian Ginseng) and Shilajit Differentially Affects Cholinergic but Not Glutamatergic and GABAergic Markers in Rat Brain. Neurochem Int. Feb1997;30(2):181-90.
  37. View Abstract: Andallu B, Radhika B. Hypoglycemic, Diuretic and Hypocholesterolemic Effect of Winter Cherry (Withania somnifera, Dunal) Root. Indian J Exp Biol. Jun2000;38(6):607-9.
  38. View Abstract: Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the Regulation of Circulating Thyroid Hormone Concentrations in Female Mice. J Ethnopharmacol. Nov1999;67(2):233-9.