The major driving force for the growth of the dietary supplements market is the perception that 'they are safe because they are natural'. However, the recently reported cases of hepatotoxicity induced by natural substances (8
) indicate that natural substances may not be entirely safe.
There are about 400 species of aloe. Among them, particularly aloe vera
has been used in phytomedicine. There have been positive reports on aloe vera
as anti-inflammatory, anticancer, analgesic, anti-aging as well as liver protective. But, clinical effectiveness of aloe vera
was not sufficiently defined because there were no large and randomized studies (9
). In 1994, Korea's National Institute of Safety Research conducted an experiment on the efficacy and toxicity of aloe (10
). There was no difference of natural killer cell activity between the aloe vera
gel treated and control animals. To observe the toxicity of aloe gel, rats were given the high dose aloe orally. Any adverse effects were not detected in hematological test, serum biochemistry, and histopathological examination.
There are no specific tests or diagnostic criteria for herbinduced hepatic injury. Careful history taking, laboratory finding, and histopathology are used to diagnose it. The best way to determine causing agent is re-challenging. But it is not ethical and not applicable. Instead, the RUCAM scale is used (7
Since patients usually do not regard dietary supplements as 'real' medicine, they may fail to mention it when physicians query medication history. Physicians should keep in mind that dietary supplements can be the cause of hepatotoxicity when querying medication history, and should educate the lay public.
There are three types of acute liver injury by drug or herb (12
): hepatocellular, cholestatic, and mixed type. Our cases are characterized as hepatocellular; there is a predominant initial elevation of the ALT level. There are two proposed pathogeneses of drug induced liver disease (13
): direct toxicity and idiosyncratic mechanism. It is more likely that an idiosyncratic immunological mechanism (hypersensitivity) is responsible for the cases. A role for hypersensitivity is further supported by the presence of eosinophilic granulocytes in the periportal fields seen in the biopsy. Hypersensitivity to aloe has been described in humans (14
), and the patch test or allergic skin test showed positive results (15
Herb induced liver injury is an important problem in clinical setting, because it can be an etiology of undiagnosed acute hepatitis. However, there are few available data about the incidence and clinical manifestation of dietary supplements such as aloe. Our cases emphasize that physicians should consider various dietary supplements as causative agents for hepatotoxicity.