Ashwagandha

Claimed to reduce stress and cortisol, reduce anxiety, improve sleep, raise testosterone, increase strength and VO2max and improve cognition. The pooled trial effects are enormous by psychiatric standards — anxiety SMD −1.55 (95% CI −2.37 to −0.74) and stress SMD −1.75 (−2.29 to −1.22), larger than most licensed anxiolytics — which is a red flag rather than a selling point. Heterogeneity was I² 93.8% and 83.1%, meaning the pooled trials are measuring substantively different things, or are differently biased, or both. The authors themselves rated the certainty of evidence LOW for both outcomes and concluded higher-quality studies are needed to establish efficacy. Funding of the individual included trials was not reported and could not be verified, which matters because the field is dominated by trials of proprietary branded extracts.

There is a confirmed hepatotoxicity signal, and it does not live in the trial literature. A case series from Iceland and the US Drug-Induced Liver Injury Network describes five patients, all of whom developed jaundice after a latency of 2–12 weeks, with a cholestatic or mixed injury pattern and prolonged pruritus and hyperbilirubinaemia lasting 5–20 weeks; chemical analysis confirmed ashwagandha in the available supplements with no other toxic compounds found. Hepatotoxicity has not been reported within clinical trials, and the anxiety meta-analysis did not analyse safety outcomes at all.

Safety knowledge is limited and Europe is moving against it: Denmark banned it in food and supplements in 2023 on the basis of a risk assessment that could not set any safe intake level, thyroid-function effects have been flagged independently by Germany, the Netherlands and the United Kingdom, and reproductive and sex-hormone concerns are on the record including traditional use as an abortifacient. Trials are short, small and report harms poorly.