Abstract
Curcuma longa is a perennial herb that belongs to the Zingiberaceae family. To date, literature includes more than 11.000 scientific articles describing all its beneficial properties. In the last 3 decades various surveys by the U.S. Food and Drug Administration (FDA) concluded that curcumin, the most active ingredient of the drug, is a “generally safe” compound with strong anti-oxidant effects. Curcuma longa was introduced in the daily diet by ayurvedic teachers due to its beneficial effects on health. Nonetheless, recently several reports, from the various global surveillance systems on the safety of plant products, pointed out cases of hepatotoxicity linked to consumption of food supplements containing powdered extract and preparations of Curcuma longa. The latest trend is the use of Curcuma longa as a weight-loss product in combination with piperine, which is used to increase its very low systemic bioavailability. Indeed, only 20 mg piperine, one of the alkaloids found in black pepper (Piper nigrum), assumed at the same time with 2 g curcumin increased 20-fold serum curcumin bioavailability. This combination of natural products is now present in several weight loss supplements containing Curcuma longa. The enhanced drug bioavailability caused by piperine is due to its potent inhibition of drug metabolism, being able to inhibit human P-glycoprotein and CYP3A4, while it interferes with UDP-glucose dehydrogenase and glucuronidation activities in liver. While only few cases of hepatotoxicity, assessed using Roussel Uclaf Causality Assessment Method (RUCAM) method, from prolonged intake of piperine and curcumin have been reported, it would be reasonable to speculate that the suspected toxicity of Curcuma longa could be due to the concomitant presence of piperine itself. Hence, not only there is the need of more basic research to understand the etiopathology of curcumin-related hepatotoxicity and of the combination curcumin-piperine, but human trials will be necessary to settle this dispute.
Highlights
The aim of this short review is to trigger a more critical evaluation of scientific evidence existing in literature on potential hepatotoxicity of Curcuma longa
In the last decade a large number of reports have been published on the beneficial effects of curcumin (Barchitta et al, 2019) and it has been repeatedly claimed that this natural product is efficient and safe for the prevention and treatment of several diseases (Abd El-Hack et al, 2021)
The co-administration of curcumin with naturally occurring UDP-glucuronyl transferase (UGT) inhibitors, like piperine, improves curcumin bioavailability compared to curcumin alone (Shoba et al, 2007)
Summary
The aim of this short review is to trigger a more critical evaluation of scientific evidence existing in literature on potential hepatotoxicity of Curcuma longa. The Compendium of Sushruta, the foundational text of Ayurveda dating to 250 BCE (Joshi et al, 2017), recommends an ointment containing turmeric, Curcuma longa powdered, to relieve the effects of poisoned food. It is not surprising, that curcumin is currently sold as a dietary supplement and that numerous clinical trials are ongoing to evaluate curcumin activity. Food supplements containing Curcuma longa have been widely used by an increasing number of consumers and there is accumulating evidence that curcumin may not be so effective and safe. Piperine’s bioavailability enhancing property is partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border (Meghwal and Goswami, 2013)
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