Can usnic acid cause hepatotoxicity?/nThe question concerns a woman who presented with symptoms of

Fråga: Can usnic acid cause hepatotoxicity? The question concerns a woman who presented with symptoms of acute hepatitis, with a tenfold increase of transaminases and icterus, after having taken the weight loss agent usnic acid (Termoxical). Virus serology was negative, and no other causes of liver damage was apparent.

Sammanfattning: Several case reports have described hepatotoxicity of various degree in persons taking usnic acid for weight loss.

Svar: Termoxical is sold over the internet as a herbal remedy for weight loss. Each tablet contains 10 mg of usnic acid, which is taken up to ten times a day (1).

One case report, describing a young, previously healthy woman, who developed fulminant liver failure after taking pure usnic acid, has been published. She presented with liver values over ten times higher than reference values and scleral icterus. Hepatitis serologies, HIV and nuclear and smooth muscle antibodies were all negative. After four days she underwent liver transplantion. At a routine physical examination two months prior to this event she had normal laboratory tests. Later it was revealed that she had started treatment with usnic acid one month prior to the liver failure (2).

Reports of hepatotoxicity after LipoKinetix ingestion have also been published (3,4,5). LipoKinetix is a herbal remedy for weight loss containing 100 mg sodium usniate (the salt form of usnic acid), 25 mg norephedrine, 100 ug diiodothyronine, 3 mg yohimbine and 100 mg caffeine. In one case series, seven cases of hepatotoxicity in connection to LipoKinex treatment are described. Symptoms characteristic of acute hepatitis appeared 1-3 months after introducing LipoKinetix. All recovered after discontinuing LipoKinetix, and liver values normalised within four months (in the five patients tested). No one was taking any prescription- or over the counter drugs. However, four persons were taking other supplements concomitantly (3). In another case series, hepatotoxicity with massive elevations of transaminases and bilirubin in two young women taking LipoKinetix is reported. The symptoms appeared two and six weeks after treatment began. One patient had to undergo liver transplantation, the other recovered after eight weeks. The patients did not take any other drugs or supplements (4). In a study, all patient cases referred to a liver transplantation service for fulminant hepatic failure during one and a half year were investigated. Ten out of a total of twenty cases had used a herbal remedy thought to be hepatotoxic. Two out of these had taken LipoKinetix. One patient had used LipoKinetix for months, and the other for one year, before the event. One of the patients died (5).

Studies of mouse hepatocytes have shown a hepatotoxic potential of usnic acid (6,7). The results from a study of cultured mouse hepatocytes suggest that usnic acid directly inhibits mitochondrial function and induces oxidative stress, which leads to cell death (6).

We recommend this case be reported to the Swedish National Food Administration.