Ashwagandha (Withania somnifera)

REPORTED IN CLINICAL TRIALS (300–600 mg/day standardised extract, 8–12 weeks):• Gastrointestinal: nausea, loose stools, abdominal discomfort — mild, transient. Incidence approximately 5–10% in trials. Predominantly associated with fasting administration. Resolves on dose reduction or food co-administration.• Sedation or drowsiness: reported in a minority of patients, particularly at higher doses or bedtime dosing. Consistent with Nidrajanana (sleep-promoting) karma.• Thyroid hormone elevation (T3 and T4): documented as a pharmacological effect in 1 RCT in subclinical hypothyroid patients (Sharma et al., 2018). In patients with hyperthyroidismOveractive thyroid — the thyroid gland produces too much hormone, causing rapid heart rate, weight loss, and anxiety. or Graves' disease, or those on levothyroxineSynthetic thyroid hormone (T4) — the standard treatment for hypothyroidism. Many herbs and foods can alter its absorption or metabolism., this effect is clinically dangerous rather than beneficial.SERIOUS ADVERSE EVENTS — HEPATOTOXICITY SIGNAL: Multiple published case reports (2020–2023) have documented drug-induced liver injury (DILIDrug-Induced Liver Injury — liver damage caused by a medication, supplement, or herbal product.) temporally associated with Ashwagandha supplement use. Björnsson HK et al. (2020, Med Case Rep Rev 3(2)) reported the first well-documented cases. A subsequent case series (Björnsson ES et al., 2022, Liver Int 42(12):2716–2722) identified 5 cases of cholestatic or mixed hepatotoxicity in patients using Ashwagandha supplements. Liver biopsy in several cases showed cholestatic hepatitis pattern. All cases resolved after discontinuation; no fatalities reported. The specific withanolide responsible has not been identified. The hepatotoxicity rate is not established because the number of exposed individuals globally is not known — but the signal is real and clinically documented.

• Hyperthyroidism, Graves' disease, or thyroid cancer — Ashwagandha significantly increases T3 and T4 (confirmed human RCT); may worsen hyperthyroid state or cause thyroid storm• Concurrent levothyroxine (T4) therapy — documented thyroid hormone elevation requires dose review and TSH monitoring before and 4 weeks after initiating Ashwagandha• Autoimmune conditions (rheumatoid arthritisAn autoimmune disease where the immune system attacks joints, causing chronic inflammation, pain, and eventually joint damage., SLE, multiple sclerosis, psoriasis) — immunostimulatory activity demonstrated in vitro and animal models; may exacerbate autoimmune activity; no human safety data in autoimmune populations• Transplant recipients on immunosuppressive therapy — theoretical immunostimulatory antagonismWhen one substance reduces or blocks the effect of another — the opposite of synergy. of cyclosporineAn immunosuppressant drug used after organ transplants — metabolised by CYP3A4, making it vulnerable to many drug and herb interactions. or tacrolimusA potent immunosuppressant used in transplant patients — extremely narrow therapeutic window; small changes in drug levels can cause rejection or toxicity.• Pre-existing liver disease or elevated transaminases — hepatotoxicity signal requires baseline LFT assessment; avoid if ALT or ASTAspartate aminotransferase — another liver enzyme. Elevated with liver damage but also with muscle injury. >2× upper limit of normal• Pregnancy — animal studies show uterine contractile activity; no human safety data; contraindicated• Concurrent sedative or CNS depressant medications — additive sedation possible• Prostate cancer (hormone-sensitive) — testosterone-increasing effect; avoid without oncologist review