A session of the annual summer meeting of the Toxicology Forum, which continues today, focused on dietary supplement AERs and included a Health Canada official, a liver disease expert, a product safety specialist and a pharmacy researcher. The experts agreed that the complexity of the issue is daunting, especially the issue of gathering hard data, both in terms of who is using the products and what exactly is in them.
“The literature is not terribly robust,” said Scott Jordan, PhD, of the Marketed Health Products Directorate of Health Canada. “We integrate all available information to make a decision, not just adverse event reports.”
In the case of pharmaceuticals, when looking at an adverse event report, investigators can pull lot numbers that can be traced to the very pharmacy in which the product was sold, said Richard Kingston, a post market surveillance expert who is a professor at the University of Minnesota. A patient’s medical records an input from their health care provider can give insight into his or her compliance with the prescription instructions as a starting point. And, of course, most pharmaceuticals are designed around a single active compound, simplifying the toxicologist’s task.
Similar data is lacking for the most part in the dietary supplement realm, Kingston said. Customers generally use the products without the advice of a health care professional. Most supplements contain at least several actives (in the case of full-spectrum botanical extracts, this could number in the hundreds) and, as such, there are no blood tests that could provide data on how much of a given product a patient may have taken. And there is little hard data on the total number of doses that are actually consumed in the marketplace.
"I look at adverse events as associations," Kingston said. "I don't use the term causality, especially in the dietary supplement realm."
"There is a lot of background noise in this market," he said.
Rare, but serious events
The experts generally agreed that supplements overall present low risk, with a couple of important exceptions, one being St. John’s Wort, an herb whose drug interactions are fairly well known. Still, case of hepatotoxicity can occur, said Dr. Victor Navarro, of the Center for Advanced Liver Disease and Transplantation at the the Einstein Healthcare Network in Philadelphia. It would be little consolation to a patient who loses a transplanted liver, for example, to learn that theirs is an exceptional case.
“As clinicians, we live in the numerator. These events are rare, but when they do happen, they are serious,” he said.
Navarro said that among dietary supplements, the chief problem product categories for liver injury are bodybuilding supplements and weight management products, which should come as no surprise to those familiar to the industry. Of 109 dietary supplement products associated with hepatotoxicity events in the Drug Induced Liver Injury Network database for 2012, 36 (or 33% of the total) fell into the bodybuilding category. Another 28 events (26%) were classified as weight management.
Indeed, the image of a young male patient who’s itchy and jaundiced is becoming familiar, Navarro said. “You can spot them coming,” he said.
Many of the products that Navarro tested at his lab were adulterated with non dietary ingredients, such as steroids. Navarro raised a point echoed by several audience participants. “We have done some studies in which undeclared steroids are commonplace. Is this even a dietary supplement at all?” he said.
To Jordan, that’s something of a moot point. As a guardian of the public health, Jordan said his agency must act if it sees an issue, whether or not an industry might feel unfairly tainted in the process.
“If we think something it is going to cause a problem, we have to make a decision,” he said. “If it’s a quality issue, it doesn’t really matter what the label says. We want to take the product off the market.”
Improving compliance
All of the speakers agreed that the reporting of adverse events needs to be improved. The current situation falls far short of a system that can really protect public health.
“We know there is substantial underreporting,” Jordan said. “We estimate only about 1% or less (of potential adverse events associated with supplements) are actually reported.”
Jordan says Health Canada is working on ways to improve the AER situation, including educating potential reporters such as naturopaths and other clinicians on what the agency is looking for in terms the data that should be contained in a report. The situation is somewhat easier in Canada, he noted, because the pre market licensure process there captures a lot of data on a product that can be quickly retrieved via the product’s license number.
Kingston said more education would help in the US, too. And, he said, a method of recognizing companies that are good AER citizens in a way that could provide them a market advantage could improve compliance.
But the speakers acknowledged that many of the black marks on the adverse events scene—as in so many other areas of dietary supplement quality—come from fly-by-night internet marketers.
“God bless the global marketplace,” Jordan said. “It’s wonderful and it’s horrible at the same time. You can’t monitor it in its totality. It’s almost impossible to police it.”