TGA Safety Advisory – Withania somnifera

The TGA has published a safety advisory regarding emerging reports of gastrointestinal symptoms associated with the ingredient Withania somnifera (also known as Ashwagandha). The TGA also provide that in very rare cases Withania somnifera, may contribute to liver injury.   

A number of gastrointestinal reactions (including significant nausea, vomiting and diarrhoea) were noted by the TGA, who provided that reactions resolved after discontinuation of the product, but 16 cases were still severe enough to require hospitalisation. While some of these cases involved other ingredients known to cause gastrointestinal side effects, the TGA state severe reactions requiring hospitalisation are not expected from these ingredients. However, the TGA note that it is still possible they may have contributed in some cases.   

The safety advisory notes that the TGA has received 12 reports of liver problems experienced by consumers taking products containing Withania somnifera up to 5 February 2024, in addition to some international reports. Seven of these reports were stated to have had enough information to suggest a liver injury that may have been caused by Withania somnifera. In 4 of these cases there were no other ingredients likely to have contributed to the liver injury. The other 3 cases involved additional products or ingredients that may have contributed to liver injury. Most patients recovered after they stopped using Withania somnifera, although some required medical treatment. Four cases required hospitalisation. 

Due to CMA’s suggestions/requests, the TGA have included information about the risk of buying overseas products from online retailers that are not regulated by TGA for quality and safety, including wasting their money or risking their health, and advised how consumers can identify Australian-regulated products with strict manufacturing standards by their AUST L or AUST R number. The TGA have also identified that some of the liver damage involved such products purchased from overseas online retailers. 

Member Considerations  

The root of Withania somnifera, typically used in herbal medicines, contains various chemically bioactive components and has been used in Ayurvedic medicine for centuries for a range of health benefits. Withania root was adopted by traditional Western herbal medicine and has gained wide popularity for supporting resilience during stress. Recent scientific studies provide support for this use.1 

Assessing the risks and benefits of Withania somnifera is complicated by the variety of extracts used in listed medicines, made with different solvents and extraction methods and standardisation against different marker constituents. Members are encouraged to contact CMA if they have particular insights into any of the adverse reactions reported and the type of plant parts or extracts they were associated with. 

Medicines containing Withania root have been permitted for use in Australia for over 30 years, and there are around 370 products containing Withania on the Australian Register of Therapeutic Goods. Over 30 clinical trials internationally have considered its safety and efficacy. In 2020 a major review was published of twenty randomised controlled trials examining the safety and efficacy of Withania with over a thousand participants.2 In fifteen of these trials no treatment related adverse events were reported. A small number of people in the other trials reported mild, mainly transient symptoms. The most common, experienced by less than 5% of people included stomach discomfort and loose stools, with no serious adverse events.2 

While several reports of liver injury (other than the new TGA reports) associated with supplementation with Withania somnifera have been published recently, a proportion of the individuals concerned had serious pre-existing liver conditions.3 Other reports provide no medical history.4 

In 2023, a review examined biological markers of health status measured before participants took Withania supplements and again at the end of the study. Three studies monitored the liver enzymes which are key biochemical indicators of Herb Induced Liver Injury (ALP, ALT and AST). The levels of these enzymes remained within healthy range.5 Finally, a 2021 a systematic review of 12 studies, trialling a range of doses of Withania including extracts standardised to 5% and 10% withanolides and 35% withanolide glycosides, in healthy people found no serious health concerns.6  

CMA is developing a public media release and will keep members informed via alerts or our newsletter of any further important developments. 

CMA encourages members to contact CMA in confidence to advise of any emerging information that they are aware of on this, or other issues related to herbal ingredients via technical@cmaustralia.org.au.  

Sponsor Regulatory Response 

CMA informed members between March and April 2023, via the CMA Supplement Newsletter, of the TGA Advisory Committee on Complementary Medicine (ACCM) November 2022 meeting statement, which provided that the committee was asked to consider the potential for Withania somnifera to cause herb-induced liver injury. This is likely as a result of emerging national and international safety signals, which members may be aware of as part of their regular monitoring activities.  

CMA encourages members to be aware of the pharmacovigilance and reporting responsibilities of medicine sponsors and to review the mandatory pharmacovigilance requirements and best practice pharmacovigilance obligations. The TGA accept a risk-based approach which is generally is expected to include more regular monitoring of ingredients associated with adverse events. 

The TGA advise sponsors within the alert of Withania somnifera products to take appropriate risk mitigation action, if the available evidence alters the risk-benefit profile for their products. 

CMA notes that this Safety advisory may foreshadow a TGA proposal to include a liver warning statement on complementary medicines containing Withania at the next annual Permissible Ingredients Determination Consultation in August- September this year. 

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