The information was presented by Dr Victor Navarro, the chair of hepatology at the Einstein Healthcare Network in Philadelphia, at the gathering which is called The Liver Meeting and which concludes today in Washington, DC. Navarro presented the results of a study conducted using data culled from the Drug Induced Liver Injury Network (DILIN).
Supplement-related liver injury increasing, researchers conclude
Researchers looked at 845 cases involving patients who, according to the information in the database, either probably, very likely or definitely experienced liver injury as a result of the suspected agent in each case.
Two hundred sixty-two herbal dietary supplements (HDS) were used by 136 patients with HDS-induced liver injury (HILI). After excluding seven patients who used a combination of HDS, the evaluated cohort included 44 patients who used HDS for bodybuilding, 85 who used HDS products marketed for other purposes, and 709 who experienced drug-induced liver injury (DILI).
None of the bodybuilding group needed a liver transplant, compared with 13% of the general supplement group and 3% of prescription drug users. The bodybuilding product users were hospitalized more frequently, but none of them died, whereas 4% of other HDS users and 7% of prescription drug users died.
The researchers concluded that liver injury as a results of herbal supplement use increased from 7% of cases between 2004 and 2005 to 20% between 2010 and 2012.
Including bodybuilding products in the data set is sure to raise eyebrows among those familiar with herbal supplements. Many of these products use herbal names on their labels, but whether the ingredients actually come from botanical sources is another question, as is the issue of whether they contain undeclared active pharmaceutical ingredients.
Manufacturers not contacted
Leaving that point aside, the question does raise the issue of what exactly is an herbal supplement, anyway? Who defined the substances included in the reports that form the database?
“I’ve always had a question about this and I’ve made that clear in presentations,” Rick Kingston, PharmD, president of regulatory and scientific affairs at SafetyCall International told NutraIngredients-USA.
“They are using a causation model that really doesn’t include an entity that has the most at stake and that is the manufacturer. They try to identify what they think is a dietary supplement and I don’t think they are doing as good a job as they could if they talked to the manufacturers,” said Kingston, who is also a professor of pharmacy at the University of Minnesota.
Kingston illustrated his point with a real life example in which researchers associated with the data base linked a liver injury case with ingredients in a supplement using information culled from a website. But, as they had not contacted the manufacturer, they didn’t realized they were using information from a product that had not been on the market for at least 10 years.
“They do a causation analysis and that analysis is based on the ingredients that they believe are in that dietary supplement,” Kingston said. “They did a very eloquent write up of the ingredients they thought were in the product.”
Database could be useful tool
Kingston emphasized he is not trying to denigrate the value of the work connected to the DILIN. He believes, though, that opening up the lines of communication between manufacturers, regulators and healthcare professionals could vastly improve the quality of the data as it relates to dietary supplements. As it stands, lumping all of the events under the umbrella of “herbal dietary supplements” is not precise enough to draw usable conclusions, especially as those products may be poorly characterized in many reports. Many products contain multiple ingredients, any one of which might be the culprit in a liver injury event.
“Just to simply say that dietary supplements cause liver injury is really not very informative for anybody,” he said.
Improving the way DILIN data is gathered and collated could make it a more powerful tool for identifying cases of real concern, Kingston said.
“All the stakeholders here want to see good information. If we think back on what happened with ephedra, there are some circumstances where we might want to look at a combination product. It wasn’t until ephedra was mixed with other stimulants like caffeine that you started to see problems,” he said.