Ashwagandha

Synonym(s): alkaloids, Indian ginseng, poison gooseberry, winter cherry, withanolide

Nutrient group: plant extracts & active ingredients

Sources and physiological effects

Dietary sources
Ashwagandha originates from India and has been used in Ayurvedic medicine for more than 3000 years. Laboratory analyses have identified more than 35 chemical components contained in the roots of Withania somnifera [1]. The biologically active chemical components include alkaloids (pelletierine, anaferine), steroidal lactones (withanolides, withaferins) and saponins. Withania somnifera is also rich in iron. The roots consist primarily of compounds known as withanolides, which are believed to have a medicinal effect. Withanolides are steroidal and have a similar effect to ginsenosides, the active components of Asian ginseng (panax ginseng). Ashwagandha is therefore also known as Indian ginseng.
Physiological functions
Inflammation	Inhibition of inflammation though the biologically active steroid withaferin A
Immunomodulation	Positive influence on the B- and T- lymphocytes
Blood	Lowers total lipids, cholesterol levels and triglycerides in the blood Increases plasma HDL cholesterol levels, HMG-CoA reductase activity and bile acid content in the liver

Indications

Dosing	Indication	Dosage
Physiological effects at low a low intake	Supportve in times of increased stress	500 mg/d
	For support of sleep disorders	50 mg/d
	For Long COVID	600 mg/d

Interactions

Drug interactions
Blood pressure lowering medication (antihypertensive medication)	As Ashwagandha can lower blood pressure, taking it in combination with medication to treat high blood pressure can cause blood pressure to drop too low
Immunosuppressive drugs	Ashwagandha can lead to increased activity of the immune system and impair the effect of immunosuppressants
Sedatives (benzodiazepines)	Ashwagandha may cause drowsiness. If tranquillizers are taken in combination with Ashwagandha, their effect may increase
Thyroid hormones	Ashwagandha may increase the production of thyroid hormones in the body. Combination usage of medication to increase thyroid hormone production and Ashwagandha can lead to an excessive concentration of thyroid hormones in the body and increase the effects and side effects of thyroid hormones
Medications that lower blood sugar	Ashwagandha may reduce blood sugar levels. A combination of blood sugar lowering medication and Ashwagandha may lead to an excessive decrease in blood sugar. Therefore, blood glucose levels should be monitored very closely and the diabetes medication dosage adjusted if necessary

Detailed information

Wide spectrum of action

Centuries of Ayurvedic medical experience with Withania somnifera have shown that the plant has pharmacological value as an adaptogen, antibiotic, abortive agent, aphrodisiac, astringent, antiphlogistic, diuretic, narcotic, sedative and tonic. Another important effect is its strong antioxidative effect [2, 3]. Ashwagandha also activates immune cells including lymphocytes and phagocytes [4, 5]. It also counteracts stress and promotes general well-being [6].

Anti-inflammatory activity

Withaferin A contained in the roots of Ashwagandha has a fairly strong antiarthritic and anti-inflammatory effect. The anti-inflammatory effect can be traced back to biologically active steroids, the main component of which is Withaferin A. This enables Withaferin A to suppress arthritic syndrome efficiently and without toxic effects. In contrast to animals treated with hydrocortisone for arthritic syndrome, which lost weight, animals treated with Withaferin A gained weight. In adjuvant-induced arthritis in rats, which is an experimental approach to investigating human rheumatoid arthritis, Withaferin A demonstrated a stronger effect than hydrocortisone. At a dosage of 12–25mg/kg body weightt, edema-inhibiting activity was also observed. A single dose suppressed inflammation for four hours after administration [7]. Detailed studies investigated the release of serum-β-1-globulin during the primary phase of adjuvant-induced arthritis and formaldehyde-induced arthritis. These experiments showed positive effects after a short time, including a reduced degree of inflammation [8].

Ashwagandha for the reduction of stress and restlessness

A study by the Institute of Medical Foundations at the University of Calcutta investigated the effects of Ashwagandha on chronic stress in rodents. Stress in animals leads to hyperglycemia, glucose intolerance, increase in plasma corticosterone levels, stomach ulcers, male sexual dysfunction, cognitive deficits and immunosuppression [9]. Animals receiving Ashwagandha showed a marked reduction in stress symptoms. This confirms that Ashwagandha has a significant anti-stress effect [10]. Research conducted at the Department of Pharmacology at the University of Texas shows that extracts of Ashwagandha have GABA-like activity and may be responsible for these effects [11]. GABA is a neurotransmitter in the brain that down-regulates neuronal activity and thus has a calming effect. Neuronal overactivity can lead to restlessness and insomnia, so the inhibitory effect of GABA helps to induce sleep, elevate mood and reduce anxiety. Traditional Chinese medicine uses Ashwagandha to stabilize the mood of patients with behavioral disorders. One study showed that its effects as an antidepressant and anxiolytic in rodents is comparable to those of the antidepressant imipramine and the anxiolytic lorazepam (ativan) [12]. In fact, Ashwagandha is one of the most widely used tranquilizers in India, where it has similar importance to ginseng does in China. It acts mainly on the reproductive and nervous systems, has a rejuvenating effect on the body and improves vitality and recovery after disease [13]. Chronic stress can lead to cognitive deficits, immunosuppression, sexual dysfunction, stomach ulcers, irregularities in glucose homeostasis, and changes in plasma corticosterone levels. In a rat model of chronic stress syndrome, withania-somnifera and panax-ginseng extracts were compared for their ability to mitigate some of the negative effects of chronic stress [9]. The research results show that both Ashwagandha and Panax ginseng reduce the frequency and severity of stress-induced ulcers, reverse stress-induced inhibition of male sexual behavior, and inhibit the effects of chronic stress on the memory of learned tasks. Both plants also reversed stress-induced immunosuppression, but only Withania extract increased peritoneal macrophage activity [14].

Antibiotic activity

The antibiotic effect of the roots and leaves of Ashwagandha has been demonstrated in various experiments. WithaferinA at a concentration of 10μg/ml inhibits the growth of various gram-positive bacteria as well as acid-resistant aerobic bacilli and pathogenic fungi. In addition, it has an antibiotic effect on Micrococcus pyogenes var. aureus and partially inhibits the glucose-6-phosphate dehydrogenase of Bacillus subtilis.
WithaferinA is also effective against the Ranikhet virus, the vaccinia virus and Entamoeba histolytica [15]. Another proven effect is protection against systemic Aspergillus infections. This is probably related to the activation of macrophage function, as shown by the increase in phagocytosis and intracellular death of peritoneal macrophages induced by Ashwagandha treatment in mice [16]. The antibiotic activity of WithaferinA is due to the presence of the unsaturated lactone ring. Lactone showed strong therapeutic activity in experimentally induced abscesses in rabbits, even slightly stronger than that of penicillin. This supports the reputation of leaves as a cure for ulcers and carbuncles in the Indian medical tradition [15].

Antioxidative effect

The brain and nervous system are relatively susceptible to free radicals compared to other tissues because they are rich in lipids and iron, which play a role in the formation of reactive oxygen species. Free radicals damage nerve tissue and may be involved in aging and neurodegenerative diseases such as epilepsy, schizophrenia, Parkinson's disease and Alzheimer's. Sitoindosides and WithaferinA (glycowithanolide) were tested for their antioxidant activity using superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in the rat brain. A reduced activity of these enzymes leads to the accumulation of toxic free oxygen radicals and consequently to degenerative effects. An increase in these enzymes results in increased antioxidant activity and thus protection of neuronal tissue. In studies, supplementation with glycowithanolides resulted in an increase in these enzymes [17]. Another study investigated the effects of an aqueous suspension of Ashwagandha root extract on stress-induced lipid peroxidation (LPO) in mice and rabbits. LPO blood levels were increased by lipopolysaccharides (LPS) of Klebsiella pneumoniae and peptidoglycans (PGN) of Staphylococcus aureus. Simultaneous oral administration of the extract could prevent an increase in LPO [17, 18].

Anti-Aging-Activity

Ashwagandha was tested for its anti-aging properties in a double-blind study. A group of 101 healthy men aged 50 to 59 years received the herb in a daily dose of 3g for one year. The subjects experienced a significant improvement in RBC blood levels and hair melanin. In addition, serum cholesterol levels decreased. Additionally, 70% of the study participants reported an improvement in sexual performance [19].

Effect as anticonvulsant

In animal studies, administration of Ashwagandha root extract reduces the severity of pentetrazol(PTZ)-induced cramps [20]. In addition, the intensity of motor seizures, caused by electrical stimulation induced by bipolar electrodes in the right basolateral core complex of the amygdala, may be reduced [21].

Immunomodulatory activity

Ashwagandha can also achieve significant modulation of immunoreactivity. The plant extract prevented myelosuppression in mice treated with three immunosuppressants (cyclophosphamide, azathioprine, prednisolone). In addition, the administration of Ashwagandha can significantly increase Hb concentration, RBC count, platelet count and body weight in mice [22]. Another effect was a significant reduction in cyclophosphamide-(CTX)-induced leukopenia. In animals treated with CTX, administration of Ashwagandha extract significantly reduced leukopenia and also increased bone marrow cellularity [23]. Gamma ray induced leukopenia was also significantly reduced by Ashwangandha [24]. In further studies Withanolide demonstrated specific immunosuppression of T lymphocytes, whereas WithaferinA positively influenced both B and T lymphocytes [25].

Hypolipidemic effect

In studies with hypercholesteremic animals, Ashwagandha root powder was able to reduce total lipids, cholesterol and triglycerides. Another effect was a significant increase in plasma HDL cholesterol levels, HMG-CoA reductase activity and bile acid content in the liver. There was a significant decrease in lipid peroxidation in those animals to which the root powder was administered [18, 26]. Another study investigated hypocholesterolemic, diuretic and hypocholesteremic effects of Ashwagandha root in humans. Six patients with non-insulin-dependent diabetes mellitus and six slightly hypercholesteremic patients were treated with the root powder for 30 days. Blood and urine samples were taken from the volunteers at the beginning and end of the study period. The decrease in blood glucose was similar to that of orally administered hypoglycemic drugs. In addition, a significant increase in urine sodium and urine volume and a significant decrease in serum cholesterol, triglycerides, LDL (low-density lipoprotein) and VLDL (very-low-density lipoprotein) cholesterol was measured. This indicates that Ashwagandha is a potential hypoglycemic, diuretic and hypocholesterolemic agent [27, 28].

Anticarcinogenic effect

Studies in animal cell cultures show that Ashwagandha reduces the level of NF-κB, suppresses the intercellular tumor necrosis factor and enhances apoptotic signals in cancer cell lines [28]. In further studies, Ashwagandha was used to reduce tumor size [29, 30]. A positive effect was also shown in urethane-induced lung tumors in adult male mice [31]. After the administration of Ashwagandha over a period of seven months, the histological appearance of the lungs of the animals receiving the plant was similar to that of the control animals.

Ashwagandha and Long-COVID

A recent study shows that patients with Long-COVID may benefit from ashwagandha, in which Withania somnifera can improve cardiorespiratory endurance and quality of life. In a double-blind, randomized, placebo-controlled study of fifty healthy, athletic adults, half of the subjects took 300 mg of ashwagandha root extract twice daily for a period of 8 weeks. At the end of the study, those subjects taking ashwagandha were found to have a significant improvement in cardiorespiratory endurance by maximal aerobic capacity (VO2 max). In addition, subsequent evaluation of various questionnaires revealed improvement, particularly in fatigue recovery, lack of energy, and fitness analysis [32].

Other therapeutic advantages

Other studies have shown that Ashwagandha may be effective in the treatment of osteoarthritis [33], inflammation [34], stroke [35] and tardive dyskinesia [36]. It is also a potential antimicrobial agent with antifungal activity and moderate antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa [37].

Administration

General mode of administration
When	For stress reduction, best taken before a meal. As a sleeping aid, best taken before going to bed.
Side effects
Pregnancy and lactation: Ashwagandha should only be used under medical supervision during pregnancy and lactation. Diabetes: Ashwagandha can lower blood sugar levels. In diabetics, blood glucose levels should be monitored very closely. High or low blood pressure: Ashwagandha may lower blood pressure. Therefore, you should use Ashwagandha carefully if you have low blood pressure or are taking medication for your blood pressure. Gastrointestinal ulcers: In high doses Ashwagandha can irritate the gastrointestinal tract. Therefore, it should not be used for stomach ulcers. Autoimmune diseases: such as multiple sclerosis (MS), lupus (systemic lupus erythematosus, SLE), rheumatoid arthritis (RA), etc..: Ashwagandha can lead to increased activity of the immune system and thus increase the symptoms autoimmune diseases. Surgeries: Ashwagandha can slow down the central nervous system. This effect may be enhanced by anesthesia and other medications during and after surgery. Ashwagandha should be discontinued at least two weeks prior to surgery. Thyroid Diseases: Ashwagandha may increase the production of thyroid hormones. Therefore, if you have thyroid disease, consult your doctor before taking this medicine.

References

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2) Abou-Douh, A. M. 2002. New withanolides and other constituents from the fruit of Withania somnifera. Arch Pharm (Weinheim). 335(6):267–76.
3) Panda, S., Kar, A. 1997. Evidence for free radical scavenging activity of Ashwagandha root powder in mice. Indian J Physiol Pharmacol. 41(4):424–6.
4) Wagner, H. et al. 1994. Plant adaptogens. Phytomedicine. 1(1):63–76.
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17) Bhattacharya, S. K. et al. 1997. Effect of Trasina, an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats. Indian J Exp Biol. 35(3):297–9.
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20) Kulkarni, S. K., George, B. 1996. Anticonvulsant action of Withania somnifera root extract against pentylene tetrazole (PTZ)-induced convulsions in mice. Phytother Res. 95(10):447–9.
21) Kulkarni, S. K. et al. 1993. GABA receptor mediated anticonvulsant action of Withania somnifera root extract. Indian Drugs. 305–12.
22) Ziauddin, M. et al. 1996. Studies on the immunomodulatory effect of Ashwagandha. J Ethnopharmacol. 50(2):69–76.
23) Davis, L., Kuttan, G. 1998. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol. 62(3): 209–14.
24) Kuttan, G. 1996. Use of Withania somnifera Dunal as an adjuvant during radiation therapy. Indian J Exp Biol. 34(9):854–6.
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26) Visavadiya, N. P., Narasimhacharya, A. V. 2007. Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats. Phytomedicine. 14(2–3):136–42.
27) Andallu, B., Radhika, B. 2000. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. Indian J Exp Biol. 38(6):607–9.
28) Ichikawa, H. et al. 2006. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther. 5(6):1434–45.
29) Prakash, J. et al. 2002. Withania somnifera root extract prevents DMBA-induced squamous cell carcinoma of skin in Swiss albino mice. Nutr Cancer. 42(1):91–7.
30) Jayaprakasam, B. et al. 2003. Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves. Life Sci. 74(1):125–32.
31) Singh N. et al. 1986. Prevention of urethane-induced lung adenomas by Withania somnifera (L.) Dunal in albino mice. Int J Crude Drug Res. 24(2):90–100.
32) Tiwari, S., Gupta, S. K., Pathak, A. K. 2021. A double-blind, randomized, placebo-controlled trial on the effect of Ashwagandha (Withania somnifera dunal.) root extract in improving cardiorespiratory endurance and recovery in healthy athletic adults. J Ethnopharmacol. 272:113929.
33) Kulkarni, R. R. et al. 1991. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 33(1–2):91–5.
34) Anbalagan, K., Sadique, J. 1981. Influence of an Indian medicine (Ashwagandha) on acute-phase reactants in inflammation. Indian J Exp Biol. 19(3):245–9.
35) Chaudhary, G. et al. 2003. Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats. Clin Exp Pharmacol Physiol. 30(5–6]:399–404.
36) Bhattacharya, S. K. et al. 2002. Effect of Withania somnifera glycowithanolides on a rat model of tardive dyskinesia. Phytomedicine. 9(2):167–70.
37) Choudhary, M. I. et al. 1995. Antifungal steroidal lactones from Withania coagulance. Phytochemistry. 40(4):1243–6.

References Interactions
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