Ashwagandha

“Withania Somnifera” 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.

Common Names

  • Ashwagandha
  • Indian ginseng
  • Winter cherry

Potential uses and benefits

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

Side effects

  • Nausea (feeling like you’re going to throw up)
  • Headache
  • Drowsiness
  • Stomach irritation
  • Diarrhea (loose or watery stool)

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).

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).