Withanolides
Withanolides are a group of naturally occurring steroid compounds with 28 carbon atoms. Research on the active compounds in ashwagandha (Withania somnifera) has largely focused on this group.
What it means in practice
Withanolides are a large family. They are commonly found in the Solanaceae plant family [2], and a 2011 review counted 360 new naturally occurring withanolides isolated and identified between August 1996 and March 2010 alone [1]. Named examples measured in ashwagandha research include withaferin A, withanolide A and withanoside IV [2].
The US National Center for Complementary and Integrative Health describes withanolides as one group among several bioactive compounds in ashwagandha [4].
Why it matters when reading nootropics research
Ashwagandha extracts can be sold and studied by withanolide percentage. One placebo-controlled trial tested KSM-66, an extract provided by its manufacturer Ixoreal Biomed, which was standardized to a withanolide content of at least 5% measured by high-performance liquid chromatography (HPLC) [3]. Extracts with different percentages, or measured by different methods, are not automatically equivalent.
A label percentage also says little about how much reaches the blood. Until recently it was unclear which withanolides, if any, appear in plasma after ashwagandha products are ingested [2]. A 2024 review found twenty plasma studies, sixteen in animals and four in humans [2]. Plasma levels varied significantly with the substance given, the withanolide dose and the route of administration, and in humans the reported peak concentrations (Cmax) of the withanolides measured ranged from 0.1 to 49.5 ng/mL [2].
When reading an ashwagandha trial, look for the extract name, its withanolide percentage and how that percentage was measured. For the graded evidence, see Ashwagandha.
References
- Chen LX, He H, Qiu F. Natural withanolides: an overview. Nat Prod Rep. 2011.
- Speers AB, Lozano-Ortiz A, Soumyanath A. Quantifying Withanolides in Plasma: Pharmacokinetic Studies and Analytical Methods. Nutrients. 2024.
- Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012.
- National Center for Complementary and Integrative Health (NIH). Ashwagandha: Usefulness and Safety. 2023-03.