Can Guduchi (Tinospora cordifolia), a well-known ayurvedic hepato-protectant cause liver damage?

Ayurveda is a centuries old traditional medicine practiced in India even today. There are certain safe medicinal plants with well-established medicinal properties both in clinical practice as well as in modern scientific publications. Guduchi or Tinospora cordifolia (Willd.) Miers (Menispermaceae), is one such medicinal plant that has well known anti-inflammatory, immune-modulatory and other safe therapeutic applications including hepato-protection, because of which it was recommended by the Ministry of AYUSH, Government of India to be used in COVID-19 care. Therefore, Aabha Nagral's article "Herbal Immune Booster-Induced Liver Injury in the COVID-19 Pandemic-a Case Series," published in 2021, was unanticipated. The article recounted histologically documented clinical cases of six patients who developed drug-induced autoimmune-like hepatitis after reported consumption of Guduchi or Guduchi containing formulations during the COVID-19 pandemic. Since the Ayurveda practitioners vouch by the safety of T. cordifolia (TC), it was felt that the story needed to be further scrutinized. This article reviews the botanical entities, the substitutes and adulterants of species used as Guduchi, their pharmacological and toxicological properties. While the authentic botanical entity of Guduchi is TC, Tinospora sinensis and Tinospora crispa are also commonly traded in the Indian subcontinent as Guduchi or Giloy. Among these species, T. crispa is known to induce heapto-toxicity. In Nagral's article, there were variations in the reported six cases in terms of patient history and TC/TC product consumption. More importantly, the botanical authenticity of the consumed products was not investigated. A review of published literature indicates that it is unlikely that the authentic TC could have induced autoimmune-like hepatitis of the patients. It is probable that a wrong species was self-administered by the patients. It is worth following up with the cases (patients), to investigate details of the products, so that other consumers do not suffer. Nagral's article however does highlight the serious issue of adulteration in herbal markets and the need for establishing a robust pharmacovigilant system in India.

Inherent Dangers of Using Non-US Food and Drug Administration-Approved Substances of Abuse.

Use of US Food and Drug Administration-approved substances of abuse has innate risks due to pharmacologic and pharmacokinetic properties of the medications, but the risk when using nonapproved drug products is much greater. Unbeknownst to the user, the dose of active ingredients in substances of abuse can vary substantially between different products because of manufacturing practices or improper storage. Even naturally occurring substances of abuse can have extensive dosage variability because of effects of the growing season and conditions, or differences in harvesting, storage, or manufacture of the finished products. Many illicit substances are adulterated, to make up for intentional underdosing or to enhance the effect of the intended active ingredient. These adulterants can be dangerous and produce direct cardiovascular, neurologic, hematologic, or dermatologic reactions or obscure adverse effects. Finally, an illicit substance can be contaminated or substituted for another one during its manufacture, leading to differences in adverse events, adverse event severity, or the drug interaction profile. Substances can be contaminated with microbes that induce infections or heavy metals that can damage organs or cause cancer. This milieu of undisclosed substances can also induce drug interactions. For reasons that are discussed, individuals who use substances of abuse are at increased risk of morbidity or mortality if they develop coronavirus disease 2019. Health professionals who treat patients with acute, urgent events associated with substances of abuse, or those treating the chronic manifestations of addiction, need to appreciate the complex and variable composition of substances of abuse and their potential health effects.

Levamisole-adulterated cocaine poses a concern during the COVID-19 pandemic.

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