Cover Image


View/Hide Left Panel

complete the trial (25 percent of the subjects). This evidence is somewhat inconsistent with other information on chaparral use.

There are nine reported cases of definite hepatotoxicity temporally related to chaparral use as a single known agent; there are an additional six cases of possible hepatotoxicity. Five of the exhibited documented recovery after cessation of chaparral use and one exhibited abnormal liver function upon rechallenge. One patient required an orthotopic liver transplant, but had major confounding variables, such as hepatitis C and prior drug and ethanol abuse. In all the other cases, liver function tests became significantly abnormal with clinically evident jaundice that reversed upon discontinuation of chaparral use. In at least three cases of chaparral-associated hepatotoxicity, the patient had prior history of alcohol abuse or underlying liver disease and may represent a vulnerable population.

In determining causation, one looks for a dose-response relationship. The amount of chaparral ingested ranged from 0.3 to 6 g/day over periods ranging from 20 days to “many years.” There appeared to be no dose-response relationship, although evidence of toxicity was clearly reflected in abnormal liver function tests. The absence of pharmacokinetic data or even characterization of the formulations ingested made it difficult to determine actual dose in the various case reports.

Another important factor in determining causation is characterization of the product responsible for the adverse effect. In most of the reported cases, the product ingested by the subject was simply described as chaparral capsules or tablets. This description does not reveal whether the contents of the capsule or tablet were dried, ground plant material or dried extract. Ideally, if the contents were an extract, then the solvent should have been described as well as the ratio of solvent to plant material. This is all assuming that the plant material was properly identified and that the plant parts used were fine leaves/stems. In addition, no chemical profiles were available for the products, making it difficult to compare the different doses ingested by the subjects. Further, without examination of the quality of the product, contamination or adulteration cannot be ruled out.

In only one of the 15 case reports of chaparral-associated hepatotoxicity was it reported that a chaparral tea had been ingested. This is important because the chemical profile of the product will depend upon the preparation used. Chaparral tea contains very little NDGA or other lipophilic compounds as compared with other preparations such as a dried extract prepared with an organic solvent. If NDGA is the causal agent, the content of NDGA in various preparations becomes an important variable in determining causality.

Animal studies evaluating chaparral did not show hepatotoxicity. Animal studies evaluating NDGA did not exhibit hepatotoxicity, but instead exhibited renal proximal tubular damage and cyst formation. In other stud-

The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement