In the paper, written by officials in California public health agencies, the authors combed through data from FDA’s Center for Drug Evaluation and Research for details about the offending products. In what will come as no surprise to industry watchers, almost all of these products fell into three problematical categories: sexual enhancement, weight loss, and muscle building.
Almost half (353 products, or 45.5% of the total), were marketed for sexual enhancement. These were found by the authors to have been spiked with sildenafil (Viagra), tadalafil (Cialis) or analogues thereof.
Almost as many (317, 40.9%) were marketed for weight loss. These were found to be spiked with sibutramine, an ingredient that was once marketed under the brand name Merida as an appetite suppressant drug. It was removed from the market in the United States in 2010 because of concerns about cardiovascular risks. It has been banned in many other countries as well.
The authors found that 92 products, or 11.9% of the total were marketed for muscle building. These were found to be spiked mostly with various illegal anabolic steroids.
Upward trend for two of three categories
As far as trends are concerned, the authors found that actions taken against steroid-tainted muscle building products had all but ceased after 2011. For the other two categories, there was a steady increase in offending product from the first five-year period covered by the study to the second.
Most of the tainted products had one undisclosed ingredient. But more than 20% had two or more.
The paper also correlates these raw numbers with data combed from warning letters sent to companies. The authors found a small but troubling trend of repeat offenders.
“There were 28 products named in 2 or 3 warnings more than 6 months apart. Of these products, 19 (67.9%) were reported to contain new unapproved ingredients in the second or third warning, consistent with the assumption that the FDA found the product to be adulterated more than once,” they wrote.
“These products have the potential to cause severe adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other drugs within the same dietary supplement. As the dietary supplement industry continues to grow in the United States, it is essential to further address this significant public health issue,” they concluded.
Prominent critic adds commentary
Prominent industry critic Dr Pieter Cohen, MD, Harvard Medical School, was invited to submit a commentary to the same journal that was published along with the paper. Dr Cohen sounded many of the same themes he has before, citing the relative paucity of recalls of these products as evidence of regulatory inertia on the part of FDA. Less than half of the products found in the study had been recalled, he said.
Dr Cohen did mention that FDA successfully moved to get the problematical stimulant ingredient DMAA off the market. But for other similar ingredients, such as BMPEA, the agency was less proactive. And in a more recent case, the stimulant 1,4-dimethylamylamine (also known as octodrine), which was identified as an adulterant in a paper by Dr Cohen and other authors, the agency has yet to act.
“More than FDA action will be required to ensure that all adulterated supplements are effectively and swiftly removed from the market. Congress would need to reform the Dietary Supplement Health and Education Act of 1994. One practical change would be to require firms to register supplements with the FDA prior to sale and Congress could provide the FDA with more effective enforcement tools such as immediately revoking a product’s registration if a supplement is found to be adulterated with pharmaceutical drugs,” Dr Cohen concluded.
Illegal drugs, not supplements
While not minimizing the threat these products pose to consumers, industry stakeholders observed, as they have on similar occasions in the past, that these are really illegal drugs and not dietary supplements. They merely masquerade as such, and this is distinction that FDA itself has started to make in recent years when addressing these problematical categories.
“I think the whole industry regards this as a major issue. I think it deserves attention because these are drugs known to have serious adverse events. You don’t want an unsuspecting consumer to be taking what they believe to be an herbal product if there is an active pharmaceutical ingredient in there,” said Stefan Gafner, PhD, chief science officer of the American Botanical Council.
Daniel Fabricant, PhD, president and executive director of the Natural Products Association, said attacking the current regulatory regime, which is governed by the Dietary Supplement Health and Education Act (DSHEA) for the actions of marketers who in many cases clearly intend to skirt the rules, has become a tired refrain.
“Enough is enough when trying to blame DSHEA for people doing illegal things,” he said. “These are illegal drugs.”
“FDA has the full force of law to stop this trade and we want to see FDA do everything they can. NPA is committed to working with the FDA to prevent supplements masquerading as drugs from reaching consumers and ensuring people who break the law are punished. NPA strongly supports the prosecution of criminal activity and has robust internal measures and quality assurance programs to report bad actors to authorities,” he added.
Dr Cohen emphasized that in his view, the ability for products to come on the market with no registration or initial review makes these kind of issues more likely. Stakeholders in the dietary supplement industry are starting to come around to the idea that some kind of registry might be considered. A debate on the subject is scheduled as part of the agenda for the upcoming annual meeting of the Council for Responsible Nutrition.
Loren Israelsen, president of the United Natural Products Alliance, said what was once taboo is now becoming a more above board discussion.
“The problem they are studying and describing are well known. Among the problem categories, sexual enhancement has always been No. 1, weight loss No. 2 and muscle building No.3.”
“I think we would all like to see an end to this nagging problem. If we went toward product registration, and if there was an agreement among industry, academia and regulators that that would help to solve the problem, I think the industry would be open to that,” he said.
A voluntary effort is already under way along these lines. In April 2017 the CRN inaugurated its Supplement OWL database, in which companies can enter detailed information about their supplements, including the name of the product, the name of the company and a list of ingredients.
“I think the OWL is a potential part of the solution, if we had overarching participation from members of the trade organizations and elsewhere,” said Duffy MacKay, ND, executive vice president of scientific and regulatory affairs for CRN. With comprehensive coverage, suspect products would stand out by their absence.
What's the true risk?
But MacKay took issue with Dr Cohen’s assertion that these offending products signaled a dire public health concern. After all, 776 tainted products is a drop in the bucket compared to the 50,000 or more products that are on the market, a number which would be even bigger when one factors in SKUs that have come and gone in the 10-year period covered by the study.
“These products are really obvious and easy to avoid. They have outrageous names and are sold through questionable retail outlets. I think we can pretty easily protect consumers from every buying any of these,” he said.
Source: JAMA Network Open
October 12, 2018. doi:10.1001/jamanetworkopen.2018.3337
“Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings”
Authors: Tucker J, Fisher T, Upjohn L, Mazzera D, Kumar M
Source: JAMA Network Open
October 12, 2018. doi:10.1001/jamanetworkopen.2018.3329
Invited Commentary: “The FDA and Adulterated Supplements—Dereliction of Duty”
Author: Cohen PA