The study, published online yesterday in the Journal of Medical Toxicology, aimed to delineate the epidemiology of dietary supplement exposures in the United States by looking at calls to poison control centers in the 2002 to 2012 time frame. The authors found overall that calls about dietary supplement exposures had increased. The study found the rate of calls regarding dietary supplement exposures increased 46.1% during 2000 to 2002, decreased by 8.8% during 2002 to 2005 and increased again by 49.3% from 2005 to 2012. The authors postulated that the decrease from 2002 to 2005 most likely was a result of the Food and Drug Administration’s ban on ephedra.
The authors noted that 70% of dietary supplement exposure calls occurred among children younger than six years old and the majority of these were unintentional. Most exposures (97.3%) occurred at home, and in more than 97% of the cases, the child swallowed the substance. The authors said that serious medical outcomes accounted for 4.5% of exposures.
In a press release that accompanied the publication, an alarmist note was sounded by the study’s lead author, Gary Smith, MD, director of the Center of Injury Research and Policy at Nationwide Children’s, a hospital in Columbus, OH.
“Many consumers believe dietary supplements are held to the same safety and efficacy standards as over-the-counter medications. However, dietary supplements are not considered drugs, thus they are not required to undergo clinical trials or obtain approval from the FDA prior to sale, unless the product is labeled as intended for therapeutic use,” Dr Smith said.
Methodology questioned
Experts in the reporting of dietary supplement adverse events took issue with the study’s methodology and the threatening tone of the press release.
“I would disagree with the authors that most people think that dietary supplements are regulated in the same way as drugs. I think most people know they ARE regulated, but they are not regulated in the same way as drugs,” said Dr Stephen Schmitz, MD co-founder of the consulting firm Supplement Safety Solutions.
Rick Kingston PharmD, who is a clinical professor of pharmacy at the University of Minnesota and is the president of regulatory and scientific affairs at SafetyCall International, has for years poured over the data that can be gleaned from adverse event reports, both in the pharmaceutical realm as well as among dietary supplements. A rising tide of reports really says more about the state of the market than it does about any warning bells about safety, he said.
“It shouldn’t be a big surprise that there have been increasing numbers of exposures especially with the tremendous growth of the supplement market in recent years. Calls to poison centers involving consumer products typically are heavily influenced by market penetration,” Kingston told NutraIngredients-USA.
The press release that accompanied the publication noted that a call about a dietary supplement exposure comes in to a poison control center somewhere in the country every 24 minutes. That sounds bad, but seems trifling when put into context. Recent data shows that 70% of Americans say they are supplement users, said Dr Hector Lopez, MD, the other co founder of Supplement Safety Solutions, which, like SafetyCall International, helps companies manage the adverse events reporting process. That can be extrapolated to mean that a majority of US homes have both drugs and supplements in their cupboards. Yet Lopez said when he did a quick calculation, he found that a call about a drug exposure comes in to a poison control center every 11 seconds.
“What I think was happening with the title and the headlines on this study was that it wasn’t made clear that this was just a snapshot and is really an incomplete report of the data,” Dr Lopez said. “The majority of these calls were just inquiries and didn’t involve adverse events at all.”
Kingston agreed, saying that the title of the study could have just as well honed in on the fact that few of the calls about exposures involved adverse events.
“Unfortunately what didn’t come through as strongly as it should have in the article is that the majority of reported exposures were non-toxic in nature,”he said.
Along with the study’s apparent slant, Kingston also took issue with how the calculation of serious adverse events was done. In his view, a proper reclassification of serious outcomes leaves many fewer than 1% of the 275,000 total calls in that category.
“Also surprising is the fact that they considered the medical outcome of ‘moderate effect’ to be a ‘serious’ outcome. The AAPCC (American Association of Poison Control Centers) definition specifically indicates that moderate outcomes do not include life-threatening effects and can include such symptoms as hives. If you take out the moderate outcome cases from their serious outcome classification, it leaves only 0.2% of cases in that outcome category as compared to 4.5%,”Kingston said.
Yohimbe, energy drinks singled out
The authors voiced special concern about energy products (many of which contain caffeine) and products that contained yohimbe, most often used as an ingredient in sexual function supplements. Erectile dysfunction aids, as a product category, have suffered from adulteration concerns, with knockoff versions of sildenafil, tadalafil and other prescription vasodilators being the adulterants of choice. In the case of energy products, lawmakers made headlines in 2013 when they called company officials from energy drink companies Rockstar, Monster and Red Bull to testify on Capitol Hill about the caffeine levels in the products and their perceived penchant for marketing the products to children. The trigger event for this hearing was the case of a 13-year-old girl in Maryland with an undiagnosed heart condition who died after drinking a couple large cans of a Monster product over a 24-hour period.
“Nearly 30% of yohimbe exposure calls resulted in moderate or major effects. Yohimbe can cause heart beat rhythm changes, kidney failure, seizures, heart attack, and death . . . Energy products, including drinks, advertised to increase energy and mental performance, can cause bad clinical effects as well,” they wrote.
There were 1,818 calls concerning yohimbe in the data the authors collected. Of those, one call was associated with a death, and 23 with a ‘major outcome.’ Using the methodology criticized by Kingston, to arrive at the ‘nearly 30%’ of serious outcomes figure, the authors added in 488 ‘moderate outcome’ calls. Jumbling these different categories together muddies the waters, and makes it difficult to see if there is a true signal coming through in the data, he said. For example, Kingston said, “79% did not result in a visit to a health care provider and another 13% self-referred themselves to a healthcare provider where treatment/evaluation for a pediatric accidental exposure may or may not have been necessary.
“As for the deaths, it would have been useful to see fatality abstracts of such reports. This is especially true for reported incidents involving substances such as ginseng or homeopathic agents where such abstracts do not appear to be available in poison center annual reports,”Kingston said.
Child proof caps worth considering
Both Lopez and Schmitz said that the authors’ recommendation that yohimbe products be marketed with a child proof cap is something that might be considered by the industry.
“As a parent I am responsible for making sure my child is not able to get a hold of my dietary supplement. Perhaps child proof containers should be on those products. That’s the whole point of our business, to try to get dietary supplement companies to step up and do a bit more than what is strictly required,” Schmitz said.
Source: Journal of Medical Toxicology
An Increase in Dietary Supplement Exposures Reported to US Poison Control Centers
Online publication 24 July 2017
Authors: Rao N, Spiller HA, Hodges NL et al.