Withanolide A (Steroidal Lactone · Adaptogenic · Neuroprotective · Cognitive)
| Compound | Withanolide A |
| Chemical class | Terpenoid — Steroidal Lactone (Withanolide class, C28 skeleton) |
| CAS | 27686-84-6 |
| Primary source | Withania somnifera (ashwagandha root) |
| Key applications | Adaptogenic, neuroprotective, cognitive function, anti-inflammatory |
| Claim strength | Moderate |
| Typical form | Ashwagandha root extract standardised to total withanolides (5–10%) |
| Buy from Herbuno | Ashwagandha Root Extract Powder - Withania Somnifera | Asgandh → |
Name origin: From Withania (the plant genus) + -olide (lactone suffix). Withanolide A is the primary pharmacologically active withanolide in ashwagandha root, belonging to a class of steroidal lactones unique to the genus Withania. Over 300 withanolides have been identified, with withanolide A, withaferin A, and withanolide D as the primary bioactives. Traditional use: Ashwagandha (Asgandh in Hindi; Balya in Ayurveda — meaning "that which imparts the strength of a horse") is the most important adaptogen in the Ayurvedic tradition, used for over 3,000 years for vitality, cognitive function, reproductive health, and stress resilience. It is one of the most clinically studied adaptogens globally. Research trajectory: Withanolide A is identified as a primary neuroprotective active — it promotes axon and dendrite regeneration in human cortical neuron models (a documented mechanism shared by few botanical compounds). Multiple human RCTs for ashwagandha extract cover stress/anxiety, cognitive function, physical performance, and thyroid function. Commercial source: Ashwagandha root extract standardised to total withanolides (including withanolide A) is commercially available. See sourcing options below.
Evidence for Withanolide A Applications
Neuroprotection and axon/dendrite regeneration: Withanolide A specifically promotes axon outgrowth and dendrite extension in human cortical neurons at nanomolar concentrations — a unique mechanism among botanical compounds relevant to neurodegeneration (Alzheimer’s, Parkinson’s) and cognitive health formulations. Reduces amyloid-beta and tau pathology in AD animal models. Claim strength: Moderate (specific mechanism well-characterised; human data for extract).
Adaptogenic and stress reduction: Multiple human RCTs with ashwagandha root extract (standardised to withanolides) demonstrate significant reduction in perceived stress scores (PSS), cortisol levels, anxiety (GAD-7), and improvements in sleep quality over 8–12 weeks. Withanolide A is considered a primary contributor alongside other withanolides and withanosides to ashwagandha’s HPA-axis modulating adaptogenic activity. Claim strength: High (for ashwagandha extract); Moderate (withanolide A-specific).
Physical performance and testosterone: Human RCTs with ashwagandha extract show improvements in VO2max, muscle strength, recovery from exercise, and in some trials significant increases in serum testosterone and DHEAS. Relevant for sports performance, healthy ageing, and male health supplement positioning. Claim strength: Moderate.
Anti-inflammatory: Withanolide A inhibits NF-κB and reduces COX-2, TNF-α, and IL-6 in cell and animal models. The steroidal scaffold may contribute to anti-inflammatory activity via partial glucocorticoid receptor modulation. Claim strength: Moderate.
Ashwagandha Root Extract Powder - Withania Somnifera | Asgandh →
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Dosage & Formulator Specification
Ashwagandha extract clinical dose range from RCTs: 300–600 mg/day standardised root extract (5% withanolides), in one or two doses. KSM-66 (root-only, 5% withanolides) and Sensoril (whole plant, 10% withanolides including withasomniferols) are the most clinically studied branded extracts. Ashwagandha Root Extract Powder is commercially available — specify total withanolide content by HPLC on CoA. Withanolide A content is typically 0.5–2% of total withanolides in ashwagandha root extract; request individual withanolide profile for premium formulations.
Ashwagandha extract is well-tolerated in clinical trials up to 1,250 mg/day. At high doses, GI discomfort and rare cases of liver injury have been reported (post-market pharmacovigilance data). Standard advisory: take with food; start low and titrate. Contraindicated in thyroid disease (ashwagandha stimulates thyroid hormone synthesis — relevant for hyperthyroidism and thyroid medication interactions). Standard pregnancy advisory applies.
Frequently Asked Questions — Withanolide A
What is the difference between withanolide A and withaferin A?
Both are withanolide-class steroidal lactones from ashwagandha. Withanolide A is the primary neuroprotective active — promoting axon and dendrite regeneration. Withaferin A is the primary anticancer-researched withanolide — with stronger NF-κB covalent inhibition (at cysteine-179 of IKKβ) and antiproliferative activity in cancer cell lines. Commercial ashwagandha root extracts standardised to total withanolides co-deliver both; withaferin A is typically 0.1–0.5% of the withanolide fraction, withanolide A is typically higher. Root-only extracts (KSM-66 type) tend to have higher withanolide A relative to withaferin A compared to whole-plant extracts.
What is the difference between KSM-66, Sensoril, and standard ashwagandha extract?
KSM-66 is a branded root-only ethanol-water extract standardised to 5% withanolides — the most extensively RCT-studied format for stress, cognitive, and performance applications. Sensoril is a branded whole-plant (root + leaf) aqueous extract standardised to 10% total withanolides — with a higher withasomniferol fraction from leaves. Standard ashwagandha root extract (from Herbuno) is not a named branded ingredient but can be equivalent to KSM-66 specifications if HPLC-verified total withanolides are confirmed. For formulations referencing KSM-66 RCTs, use the branded ingredient or demonstrate equivalence.
Can ashwagandha extract affect thyroid function?
Yes — ashwagandha extract increases serum T3 and T4 levels, and reduces TSH, in human studies. This is clinically relevant for individuals with thyroid conditions: potentially beneficial for subclinical hypothyroidism, but potentially problematic for hyperthyroidism or individuals on thyroid hormone replacement. Include standard advisory language for thyroid disease and monitoring.
Is ashwagandha appropriate in a testosterone/male health supplement?
Yes. Multiple human RCTs show ashwagandha extract (300–600 mg/day) significantly increases serum testosterone (typically 10–22% above placebo) and DHEAS, alongside improvements in muscle strength and recovery in resistance-trained men. The mechanism likely involves HPA-axis modulation (reduced cortisol reducing testosterone suppression) rather than direct androgen synthesis stimulation. This is a well-supported formulation positioning with multiple independent RCTs.
Related compounds: Astragalosides, Ginsenosides, Andrographolide, Cycloastragenol
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
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