Withanolides are thought to be the primary bioactive compounds in ashwagandha. As a result, many ashwagandha supplements are standardized to contain a certain withanolide concentration in order to increase the degree of effects.
In this article, we’ll go over the benefits of withanolides, their mechanism of action, dosing guidelines, and other considerations.
Table of Contents
Withanolides Overview:
Withanolides are a group of naturally occurring steroidal lactones found in a number of species in the Solanaceae genera, most notably ashwagandha (Withania somnifera). For the purpose of this article, we will be looking mainly at the withanolides in ashwagandha.
Among the withanolides, withaferin A is the most well-studied, although there are several others with potential health effects, including:
- Withanolide D
- Withanolide A
- Withanolide sulfoxide
- Vicosalactone B
- Sominone
- And more
The withanolides act on various systems in the body and seem to exert a variety of anti-inflammatory, antioxidant, immunomodulatory, and adaptogenic effects.
Withanolides Benefits:
Research has discovered many potential health benefits of withanolides when studied in isolation and when standardized within ashwagandha extracts.
The main benefits of withanolides are:
- Stress & Anxiety Management
- Anti-Inflammatory Effects
- Immune Support
- Neuroprotection
- Anti-Carcinogenic Activity
- Muscle & Exercise Support
Note: Most of the studies listed below are not clinical trials. This is because isolated withanolides are typically studied using in vitro or in vivo methods, whereas clinical trials use the herb itself, standardized for withanolides. So, while the clinical trials are of course the most important overall, the pre-clinical trials give a better view into the isolated actions of withanolides themselves.
1. Stress & Anxiety Management
Research shows that withanolides seem to modulate the hypothalamic-pituitary-adrenal (HPA) axis, which helps the body return to balance when dealing with stressors.
In a study done on rats exposed to stress, withanolide isolated from ashwagandha decreased corticosterone levels, and also reduced various enzymes that are markers of stress in the body.
In another study done on rats, withaferin A showed anti-anxiety properties similar to diazepam (an anti-anxiety drug). Withaferin A also appeared to increase nitric oxide levels in the brain, which researchers believe may also promote anti-anxiety effects.
Another animal study found that isolated glycowithanolides led to similar anti-anxiety effects as lorazepam and comparable anti-depressive effects as imipramine (an antidepressant drug).
There are numerous clinical trials showing the benefits too, although these are used with ashwagandha extracts and not withanolide isolation. For example, one clinical trial on stressed individuals showed that 500mg of ashwagandha standardized to 2.5% withanolides led to significant reductions in stress, anxiety, and cortisol compared to the placebo.
Given the benefits seen from withanolides, it is likely that they play a key role in reducing cortisol and other stress hormones, while providing support for general stress and anxiety management.
Summary:
Lab studies have shown that withanolides may possess anti-anxiety properties and reduce stress markers in the body.
2. Anti-Inflammatory Effects
Numerous studies also highlight the potential anti-inflammatory and antioxidant effects of withanolides.
Research shows that withaferin A and other withanolides may decrease the development of various inflammatory-related diseases.
One study showed that withaferin A exhibited potent inhibitory effects on enzymes involved in inflammatory pathways, suggesting strong anti-inflammatory effects. The researchers noted this also has potential for reducing inflammatory-related issues, such as poor immune function.
In an in vitro study, withanolide extracts exhibited anti-inflammatory and protective effects on osteoarthritic cartilage cells, suggesting potential utility in arthritis and pain management.
Another in vitro study showed that various withanolides inhibited cyclooxygenase (COX)-1 and COX-2, which are enzymatic markers of inflammation. Additionally, several of these withanolides inhibit lipid peroxidation, suggesting further anti-inflammatory effects.
Summary:
In vitro studies show that withanolides may work to promote anti-inflammatory and antioxidant effects.
3. Immune Support
Withanolides also seem to support immunity. This is in part related to anti-inflammatory effects, although there may be other immunomodulatory mechanisms at play.
In one study, withanolides showed antiviral effects against Covid-19. They influenced several immune-related processes, including the control of certain proteins involved in viral severity.
A study done on mice showed that withanolide A was the most effective constituent in ashwagandha for activating T-helper cells, increasing cytokine production, and activating other important immune responses.
Another study looked into the effects of withanolide A on stress-induced immunity reductions in mice. The researchers found that withanolide A provided significant immune recovery effects, including an increase in T cells and cytokine production. Withanolide A also helped to restore glutathione levels and offered several other anti-stress activities, which resulted in improved immunity.
Interestingly, another study done on arthritic rats showed that withanolides from ashwagandha showed immunosuppressive activities, including T cell proliferation, humoral immunity, and cell-mediated immunity.
Essentially, withanolides seem to modulate the immune system depending on what is needed at that time, which is reflective of their general adaptogenic effects in the body as a whole.
Summary:
Studies indicate that withanolides may aid in immune system modulation, making this effective for immune support.
4. Neuroprotection Support
Withanolides may also have neuroprotective effects (protective effects in the brain and nervous system).
In a rat study, two different withanolide compounds showed anti-stres