Ashwagandha (Withania somnifera)

Indications

Adrenal fatigue, anxiety, and insomnia.

Mechanism of Action

The withanolides, a group of steroidal lactones, are credited with adrenal supportive effects.¹ Steroidal compounds in plants are structurally similar to human steroids, and many are noted to have numerous physiological effects.

Animal studies suggest that ashwagandha is a γ-aminobutyric acid agonist, thereby having sedative effects on the CNS.²

Evidence-Based Research

Ashwagandha has been shown to improve cancer-related fatigue in one clinical outcome study investigating breast cancer patients.³

Ashwagandha reduces activation of the hypothalamic–pituitary–adrenal axis and cortisol release in a hyper state^4,5; yet, it can increase cortisol when needed in cases of adrenal exhaustion,⁶ based on animal models of stress.

One double-blind, randomized, placebo-controlled trial evaluated the effects of ashwagandha on serum cortisol and reducing stress and anxiety. Three hundred milligrams of ashwagandha showed a significant reduction in stress, based on assessment scales in 2 months’ time relative to the placebo group, and the serum cortisol levels were substantially reduced.⁷

Effects on Stress

Ashwagandha reduces activation of the hypothalamic–pituitary–adrenal axis and cortisol release in a hyper state^4,5; yet, it can increase cortisol when needed in cases of adrenal exhaustion,⁶ based on animal models of stress. Human studies have also found a similar mechanism of action through which ashwagandha may relieve stress. One randomized, double-blinded, placebo-controlled study investigated the effect of ashwagandha in 131 chronically-stressed adults. After 8 weeks, investigators found a reduction in mild to moderate chronic stress via the modulation of the HPA axis.^5A A double-blind, randomized, placebo-controlled trial evaluated the effects of ashwagandha on serum cortisol and reducing stress and anxiety. Three hundred milligrams of ashwagandha showed a significant reduction in stress, based on assessment scales in 2 months’ time relative to the placebo group, and the serum cortisol levels were substantially reduced.⁷ Another randomized, double-blind, placebo-controlled study conducted in 2019 examined the effect of ashwagandha on 60 adults that were randomly allocated to take either a 240 mg of a standardized ashwagandha extract once daily or a placebo. Those taking ashwagandha had a statistically significant reduction in the Hamilton Anxiety Rating Scale and a near-significant reduction in the Depression, Anxiety, and Stress Scale-21 (DASS-21). Furthermore, ashwagandha intake was associated with significantly greater reductions in morning cortisol and DHEA-sulfate levels compared to the placebo group. The investigators also noticed a significant increase in testosterone levels in males, but not females. These findings suggest that ashwagandha’s stress-relieving effects may occur by modulating the effect on the hypothalamus-pituitary-adrenal axis.^7A

Effects on Anxiety

A 2023 randomized, double-blind, placebo-controlled trial investigated the effect of ashwagandha or placebo on 54 healthy individuals with mild to moderate stress and anxiety. After 60 days, investigators found that compared to placebo, 500 mg of ashwagandha root extract significantly improved symptoms of stress and anxiety by reducing cortisol and increasing serotonin levels.^7B One randomized double-blind placebo-controlled study examined the use of ashwagandha (1 gram per day) alongside conventional SSRI therapy in those with generalized anxiety disorder. After 6 weeks, a significant amelioration of Hamilton anxiety rating scale was observed, indicating a reduction in severity of symptoms in generalized anxiety disorder.^7C

Other Psychological Health Effects

A randomized double-blind placebo-controlled trial investigated the use of ashwagandha in participants with obsessive-compulsive disorder. After 6 weeks, it was shown that 120 mg per day of ashwagandha added to conventional SSRI therapy improved the severity of OCD symptoms.^7D Other studies have found benefits of taking ashwagandha in those with schizophrenia.  A randomized double-blind, placebo-controlled clinical study investigated the use of ashwagandha on 66 individuals with depression and anxiety symptoms who were diagnosed with schizophrenia. After 12 weeks, ashwagandha was found to improve anxiety and depression scores.^7E Another double-blind, placebo-controlled study examined the use of ashwagandha on individuals with schizophrenia who were on antipsychotic medication. After 12 weeks, ashwagandha was shown to significantly improve negative, general, and total symptoms, as well as stress.^7F

Male and Female Health

A 2021 randomized, double-blind, placebo-controlled study examined the effect of ashwagandha on perimenopausal symptoms in 100 women. Study participants were randomly allocated to either the treatment group (ashwagandha root extract, 300 mg twice daily) or placebo group. After 8 weeks, compared to placebo, ashwagandha supplementation was associated with a significant reduction in the total menopause rating scale score (reflected by significant reductions in the somato-vegetative, psychological, and urogenital domains). Furthermore, ashwagandha intake resulted in significant reductions in menopause-specific quality of life scores, serum FSH and LH, and a significant increase in serum estradiol compared with the placebo.^7G One randomized, double-blind, placebo-controlled, crossover trial investigated the effect of ashwagandha on 57 overweight men between 40 to 70 years of age. Investigators found that after 16 weeks, improvements in fatigue, vigor, and sexual and psychological well-being were reported over time. In addition, ashwagandha intake led to an 18% greater increase in DHEA-S and 14.7% greater increase in testosterone compared to the placebo group.^7H Another study conducted in men (a triple-blind randomized clinical trial) investigated the use of 5 grams of ashwagandha per day on sperm parameters in those with idiopathic male infertility. After 90 days, there was an increase in mean sperm count (12.5%) and progressive motility (21.42%), as well as improved sperm morphology (25.56%) compared to baseline.^7I

Thyroid Health

One prospective, double-blind, randomized, placebo-controlled trial studied the effect of ashwagandha in those with subclinical hypothyroidism. The study included 50 participants with elevated serum TSH levels, who were then randomized to either the treatment group (ashwagandha root extract, 600 mg daily) or placebo group. After 8 weeks of treatment, participants in the ashwagandha group had significantly improved serum TSH, T3, and T4 levels.^7J

Physical Endurance

A 2021 double-blind, randomized, placebo-controlled trial examined the effect of ashwagandha in 50 healthy athletic adults. Researchers found that supplementing 300 mg ashwagandha twice daily for 8 weeks enhanced cardiorespiratory endurance and improved the quality of life in these adults.^7K A recent prospective, randomized, double-blind, placebo-controlled study found that ashwagandha (300 mg capsules twice daily) taken for 8 weeks led to improvement in endurance and muscle strength in healthy adults. More specifically, ashwagandha led to significantly increased one-repetition maximum bench press and leg press, as well as greater improvements in muscle girth (for arm, chest and thigh) compared to placebo.^7L Another randomized, double-blind, placebo-controlled study studied the effects of ashwagandha on strength training in 38 recreationally active men undergoing resistance training. Researchers found that ashwagandha (500 mg per day) for 12 weeks led to improvement in upper and lower-body strength, as well as supported a favorable distribution of body mass.^7M

Insomnia

One double-blind, randomized, parallel-group, placebo-controlled study studied the effect of ashwagandha on 80 participants with insomnia. After 8 weeks, those taking ashwagandha root extract experienced significant improvements in sleep parameters (sleep onset latency, total sleep time, wake after sleep onset, total time in bed, and sleep efficiency) compared to the placebo group.^7N Another randomized-controlled trial studied the effects of ashwagandha on 60 healthy college students. After 30 days, it was found that 700 mg of ashwagandha per day resulted in lower food cravings, perceived stress, and improved sleep.^7O

Memory and Cognitive Function

A recent randomized double-blind trial examined ashwagandha use in 59 healthy individuals. The study investigators found that ashwagandha (225 mg per day) for 30 days helped improve several measures of memory, attention, vigilance, and executive function, while decreasing perceptions of tension and fatigue in young healthy men and women.^7P One prospective, randomized, double-blind, placebo-controlled pilot study studied the effect of ashwagandha on memory and cognition in 50 adults with mild cognitive impairment. After 8 weeks, those taking ashwagandha root extract (300 mg twice daily) had significant improvements in both immediate and general memory, as well as improved executive function, attention, and information processing speed.^7Q

Arthritis

A review of clinical studies found that ashwagandha may be useful in managing the symptoms of arthritis. Most of the clinical trials in the analysis used ashwagandha between 8 to 12 weeks, and at a dose of 6 grams (in powder form or extracts in tablets) or 500-1000 mg (in capsule form).^7R

Safety in Pregnancy and Breastfeeding

Historical use considered safe, but no modern research has been done on pregnancy and lactation.

General Safety

No safety concerns based on traditional dose.

Dosage

Dosage depends on whether ashwagandha is in a formula or by itself, but it is typically between 50 mg and 2 g a day of whole root.

Some manufacturers standardized to withanolide content, e.g., 1.5% withanolide content, but this varies from trial to trial, as an industry standard has yet to be established.

References

5A https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085552/

7A https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750292/

7B https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578737/

7C https://pubmed.ncbi.nlm.nih.gov/32282308/

7D https://pubmed.ncbi.nlm.nih.gov/27515872/

7E https://pubmed.ncbi.nlm.nih.gov/31046033/

7F https://www.psychiatrist.com/jcp/withania-somnifera-extract-for-schizophrenia-symptoms/

7G https://pubmed.ncbi.nlm.nih.gov/34553463/ 

7H https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438434/

7I https://pubmed.ncbi.nlm.nih.gov/29770466/

7J https://pubmed.ncbi.nlm.nih.gov/28829155/

7K https://pubmed.ncbi.nlm.nih.gov/33600918/

7L https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234080/

7M https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266766/

7N https://pubmed.ncbi.nlm.nih.gov/32818573/

7O https://pubmed.ncbi.nlm.nih.gov/35984871/

7P https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11207027/

7Q https://pubmed.ncbi.nlm.nih.gov/28471731/

7R https://pubmed.ncbi.nlm.nih.gov/34144529/