Is ashwagandha a steroid?

This plant has been used for thousands of years as a medicinal herb in traditional Ayurvedic medicine (Ayurveda). Withanolides, which are the principal bioactive compounds of ashwagandha, are naturally occurring steroids.

link.springer.com - Adrenal hypofunction associated with ashwagandha (Withania somnifera ...

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Summary

We present a case whose adrenal function was suppressed during the period when the patient was taking ashwagandha, which was reversed to normal function after discontinuation of this herbal product. As far as we are aware, this is the first observation of temporal changes in adrenal function, as assessed by SST, during and after stopping supplementation with ashwagandha. This case highlights the ability of ashwagandha to suppress adrenal function in a relatively short duration (ten weeks), but could be reversed after two weeks of discontinuation.

Clinical implications

There is a lack of scientific evidence of the effectiveness and safety of ashwagandha for treating any disease, and according to expert review from www.drugs.com website, trials supporting its clinical use in humans are limited [2]. Animal studies suggest it has effects on the immune, endocrine and central nervous systems, and inflammatory conditions. There are a handful of randomised controlled trials (RCT) from India [9, 10]. A recent RCT of sixty healthy Indian adults showed supplementation with 240 mg of ashwagandha extract once daily for 60 days led to a reduction in the Hamilton anxiety rating scale (P = 0.040) and morning cortisol levels (P < 0.001) compared with placebo [10]. The major flaws with such study were that there was no valid medical reason for lowering anxiety or cortisol levels of volunteers who were described as healthy adults. Cortisol reduction should indeed be interpreted as an adverse effect of ashwagandha rather than benefit. The subnormal adrenal response to tetracosactide (assessed by SST) observed in our patient could potentially lead to serious health consequences due to the inability of the patient to mount a response to an acute stress, such as a major illness or infection. As far as we are aware, there is no existing literature on dynamic endocrine tests of adrenal function (such as SST) during and after taking this supplement. A number of potential toxic actions associated with ashwagandha have been comprehensively reviewed and described by experts, including clinicians and pharmacists, on the www.drugs.com website [2]. Studies with Wistar rats showed that repeated injections of ashwagandha extract, at a dose of 100 mg/kg body weight for 30 days, led to reduction in the weights of adrenals, thymus and spleen [11], whilst hepatotoxicity effects of ashwagandha have recently been reported in humans [12, 13]. Dosing in humans is variable, ranging from 120 mg to 2 g a day. Contraindications and interactions and its use in pregnancy and lactation have not been well documented, but adverse effects are scarcely or inappropriately reported in human studies. For example, in two recent RCTs, one reported “no adverse events” [9] whilst the other inadequately monitored treatment safety by full blood counts and lipids [10]. Since there is no existing published literature on adrenal function amongst people taking ashwagandha, it is not possible to determine if this herbal product affects the adrenal function differently in people of different age, sex, body composition or ethnic background.

Mechanisms

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Plants have evolved to produce a number of toxic substances as defence mechanisms against predation from microorganisms (bacteria and fungi), insects and animals [14,15,16,17]. A large number of plants, including ashwagandha, used in herbal medicines possess this toxic property. The withanolides from ashwagandha contain a highly oxygenated C28 ergostane-type steroidal nucleus with C22-hydroxy-C26-oic acid δ-lactone in a nine-carbon side chain, and oxidised to form a six-membered lactone ring [18,19,20]. It is possible that the steroidal compounds from ashwagandha, such as withanolides and alkaloids, may have a direct effect on adrenal function. Adrenal steroidogenesis is complex, involving a pathway of precursor hormones that require specific enzymatic steps [21], the genes that encode the enzymes involved in the control of steroid biosynthesis may be interrupted by withanolides and alkaloids, giving rise to adrenal hypofunction. A recent study has shown that withanone, a bioactive constituent of withanolides found in ashwagandha extract, may cause deoxyribonucleic acid (DNA) damage by forming adducts to DNA. Withanone also forms adducts with amines, which are reversibly detoxified by glutathione (GSH) but may cause DNA damage when the GSH system is overwhelmed by excessive levels of withanone [22]. Studies have also found that alkaloids from a number of herbal medicines react with DNA, causing cellular toxicity or genotoxicity (damage to the genome), leading to structural alterations of the genetic material through induction of DNA binding and cross-linking, as well as chromosomal abnormalities [23]. The effects of steroidal compounds from ashwagandha may extend to higher neuroendocrine centres controlled by the hypothalamus and pituitary. The hypothalamic-pituitary axis is known to be vulnerable to stress from restricted dietary practice and excessive exercise [24] and a number of drugs including exogenous steroids and opioids [25]. It is plausible that the steroidal withanolides and alkaloids from ashwagandha could suppress the hypothalamic–pituitary–adrenal (HPA) axis, in a similar way that exogenous corticosteroids (used to treat chronic inflammatory conditions) do to the HPA axis, leading to hypoadrenalism [25, 26].

Patient perspective

The patient expressed that she would take greater caution before considering taking any dietary supplements in the future. She would do thorough research on independent sources and consult with healthcare professionals.

link.springer.com - Adrenal hypofunction associated with ashwagandha (Withania somnifera ...

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