Withanolides
Also known as: Ashwagandha withanolides, Withaferin A, Withanolide A, Withanolide B, Withanoside IV, Withanolides
Overview
Withanolides are a group of steroidal lactones found primarily in plants of the Solanaceae family, most notably in *Withania somnifera* (ashwagandha). These bioactive compounds are extracted from the plant and are recognized for their potential health benefits. They are commonly used for stress relief, improved sleep quality, and cognitive enhancement. Withanolides are characterized by their anti-inflammatory, antioxidant, and adaptogenic properties, making them a subject of growing research interest. They are available in various forms, including capsules and tablets, as part of ashwagandha extracts. While research is expanding, more rigorous clinical trials are needed to fully understand their efficacy and safety. The quality of available evidence is moderate, with many studies showing promising results but requiring further validation.
Benefits
Withanolides, primarily through ashwagandha extracts, have demonstrated potential benefits in reducing cortisol levels in stressed individuals. Studies indicate reductions ranging from approximately 16.5% to 32.63%. Some research suggests that withanolides may also contribute to increased testosterone and DHEA levels. Secondary benefits may include improved cognitive function and enhanced stress tolerance, although these effects require further investigation to confirm. These benefits are generally observed in healthy adults experiencing stress. The effect sizes vary across studies, but significant reductions in cortisol levels have been consistently noted within weeks of supplementation. The evidence suggests a potential role for withanolides in managing stress and hormonal balance, but more comprehensive research is warranted.
How it works
Withanolides interact with various biological pathways, including anti-inflammatory and antioxidant mechanisms. They may influence the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in the body's stress response. While specific molecular targets are not yet fully defined, withanolides are believed to modulate pathways related to stress and inflammation. The absorption and bioavailability of withanolides can vary, with some compounds exhibiting low oral bioavailability. Further research is needed to fully elucidate the precise mechanisms of action and optimize their bioavailability for maximum therapeutic effect.
Side effects
Withanolides are generally considered safe for short-term use, but long-term effects are not fully understood. Common side effects, occurring in more than 5% of users, include mild gastrointestinal disturbances. Uncommon side effects, affecting 1-5% of users, may include fatigue, fever, rash, diarrhea, edema, and abnormal liver function tests. Rare side effects are not well-documented. Withanolides may interact with sedatives or thyroid medications due to their adaptogenic properties. They are contraindicated in pregnancy and breastfeeding due to insufficient safety data. Caution is advised for individuals with autoimmune diseases or thyroid disorders. It is important to monitor for any adverse reactions and consult with a healthcare professional before starting supplementation.
Dosage
The minimum effective dose of ashwagandha extract, standardized to contain 5% to 35% withanolides, is typically 300 mg to 500 mg per day. Optimal dosage ranges from 300 mg to 1000 mg per day. The maximum safe dose is not well-established, but studies have used doses up to 1000 mg per day. It is best taken with meals to reduce gastrointestinal side effects. Capsules or tablets are common forms. Bioavailability may be influenced by the presence of food. No specific cofactors are required. It is advisable to start with a low dose and gradually increase as tolerated, while monitoring for any adverse effects.
FAQs
How should I take withanolides?
Take with meals to minimize gastrointestinal side effects. Start with a low dose and monitor for any adverse reactions.
Are withanolides safe?
Generally safe for short-term use, but long-term safety is less clear. Consult with a healthcare professional before use.
When can I expect to see results?
May reduce stress and improve sleep quality within weeks of consistent supplementation.
Can withanolides cure stress?
No, it is not a cure-all. Individual results may vary. It is best used as part of a comprehensive stress management plan.
What are the potential drug interactions?
Potential interactions with sedatives or thyroid medications. Consult with a healthcare provider if you are taking other medications.
Research Sources
- https://www.mdpi.com/2072-6643/16/22/3836 – This study investigates the health benefits of Ashwagandha. It provides a comprehensive review of its traditional uses, chemical composition, and pharmacological activities, highlighting its potential in managing various health conditions.
- https://pubmed.ncbi.nlm.nih.gov/39599622/ – This study examines the effects of Ashwagandha on cognitive and psychomotor functions. The research suggests that Ashwagandha may have a positive impact on cognitive performance and reaction time, indicating its potential as a cognitive enhancer.
- https://www.mdpi.com/2072-6643/15/24/5015 – This research explores the impact of Ashwagandha on sleep quality and insomnia. The findings suggest that Ashwagandha can improve sleep parameters and may be a beneficial natural remedy for individuals experiencing sleep disturbances.
- https://journals.sagepub.com/doi/10.1177/02698811231200023 – Chandrasekhar et al. (2012) conducted a randomized controlled trial (RCT) demonstrating that ashwagandha root extract reduced cortisol levels by 27.9% in stressed individuals. The study involved 61 participants over a 60-day period, highlighting the potential of ashwagandha in stress management.
- https://www.liebertpub.com/doi/full/10.1089/acm.2014.0177 – Salve et al. (2019) conducted an RCT showing reductions in cortisol levels by 16.5% and 32.63% with different dosages of ashwagandha extract. The study included 58 participants over 56 days, further supporting the stress-reducing effects of ashwagandha.
Supplements Containing Withanolides

Ashwagandha Liquid Phyto-Caps
Gaia Herbs Professional Solutions

Energy Formula With Pharma GABA & Sensoril
Natural Factors

Single Herbs Ashwagandha Root
Gaia Herbs Single Herbs

Ashwagandha Liquid Phyto-Caps
Gaia Herbs Professional Solutions

Standardized Extract Ashwagandha 500 mg
Mason Natural

Adrenal Daily Balance
Garden of Life MyKind Organics

Ashwagandha
Garden of Life MyKind Organics

Sereni-Pro
Bioclinic Naturals

Ashwagandha Root
Gaia Herbs

Ashwagandha Root
Gaia Herbs
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