During the last four years, Walmart disclosed to FDA roughly a handful of serious adverse events in connection with botanical supplements that are under investigation by New York Attorney General Eric Schneiderman, Natural Products INSIDER has learned.
Over the same four-year period, Target and Walgreens didn’t file with FDA any mandatory adverse event reports (AERs) linked to botanical supplements that New York authorities recently tested, according to data INSIDER obtained from FDA.
GNC filed just one mandatory AER that was related to a hospitalization and branded Ginkgo biloba product, the FDA data showed. The condition necessitated an intervention to prevent a permanent impairment, according to the data.
Scheiderman's office had requested information from all four retailers on AERs, which triggered our inquiry to the FDA.
Loren Israelsen, president of the United Natural Products Alliance (UNPA), said the FDA data “suggests a very good safety record" in light of the number of products that are sold by the retailers.
A spokeswoman for GNC said the 2012 AER does not relate to any product lot that is subject to the state Attorney General’s investigation. Neither the individual who filed the report nor the affected person followed up with GNC to allege a claim or file a lawsuit in connection with the referenced product, she said.
The reports, which were pulled from FDA’s post-market surveillance system and reflect national data, may provide a snapshot into whether certain supplements are potentially unsafe. The data, however, does not prove a specific product caused, or even contributed to, a death or serious illness, according to public health officials and others.
Supplement manufacturers and distributors must submit to FDA certain reports that may be associated with deaths, hospitalizations and other “serious adverse events" that a 2006 federal law defines. FDA medical officers review the so-called SAERs (serious adverse event reports) to determine if there is a causal relationship and whether the health agency needs to take action to protect the public.
The FDA data was pulled for Walgreens Finest Nutrition, GNC Herbal Plus, Walmart Spring Valley, and Target Up & Up supplement brands. These are the botanical supplement brands that Schneiderman's office tested and is investigating.
From 2011 through 2014, FDA data showed Walmart submitted to FDA just six mandatory AERs that are associated with its Spring Valley branded supplements. Two reports are associated with Spring Valley garlic supplements, two are linked to Walmart’s branded St. John’s wort supplements, and one report each was linked to ginseng and saw palmetto supplements, according to the data. In four cases, patients who reportedly consumed Walmart’s products were hospitalized, according to the data.
Walmart did not immediately provide a comment on the adverse reports. Brian Nick, a Walmart spokesman, said in an emailed statement, “The products in question have been tested using scientifically validated, widely used methods approved by governing bodies like the FDA-recognized United States Pharmacopeia [USP] and are fully compliant, safe and properly labeled."
The FDA data excludes reports that may be voluntarily submitted directly to the public health agency by consumers, physicians and others who are familiar with an adverse event associated with a product.
On Feb. 2, Schneiderman’s office advised the four retail giants that a number of their herbal supplements largely failed to contain the labeled ingredients such as St. John’s wort and were contaminated. Herbal experts and other supplement advocates have questioned the reliability of the DNA testing methodology and insisted Schneiderman's office reveal all the data from its findings.
In letters demanding the companies remove the supplements from the market, New York authorities requested information concerning the products, including all serious adverse event reports associated with their herbal dietary supplements in the United States.
Schneiderman’s office did not respond Thursday to a request for comment on FDA’s AER data.
‘No Conclusions can be Drawn’
The data “provides only a number and no supporting data to evaluate the underlying facts, and so, no conclusions can be drawn from this report as to whether a causal SAER in fact occurred," Israelsen said in an emailed statement.
Daniel Fabricant, FDA’s former top supplement official and the current CEO and executive director of the Natural Products Association (NPA), made similar observations. He said it’s not known, for instance, if other factors besides the supplement contributed to the reported illness, such as if whether the consumer was taking a prescription drug.
INSIDER could not immediately obtain detailed information on the AERs. That would require the submission of a request through the Freedom of Information Act, according to FDA.
Possible Safety Concerns
Pieter Cohen, an assistant professor at Harvard Medical School who has studied supplement safety, acknowledged the AERs don’t prove the products caused the adverse events. But he said it is conceivable the supplements could have resulted in a trip to the hospital.
For instance, Cohen said the botanical St. John’s wort is known to have adverse interactions with prescription medicines. In a Sept. 17, 2003 issue of the peer-reviewed medical journal JAMA, researchers cited case reports and formal clinical studies that indicate St. John's wort is associated with dangerous drug interactions.
In a March 2002 to February 2003 study of 12 healthy volunteers who were administered St. John's wort for 14 days, researchers concluded the results indicate long-term administration of the botanical "may result in diminished clinical effectiveness or increased dosage requirements" for certain medications, illustrating "potential problems associated with the widespread practice of using herbal products concomitantly with conventional medications." However, researchers did not find any unanticipated or serious adverse events associated with administration of the product.
Since 2000, the American Herbal Products Association (AHPA) has recommended labels on St. John's wort products that advise consumers not to take prescription drugs without a prescribing doctor's advice, said president Michael McGuffin. AHPA staff discovered through a marketplace review that a majority of St. John's products include similar labels to the one AHPA has recommended, and a number of label statements discuss potential drug interactions, McGuffin said.
“We are fooling ourselves if we think botanical supplements are always safe for every person in every situation," said Cohen, who has advocated for changes to the legal system governing supplements, in a phone interview. “Unfortunately the regulatory framework is we sell them as if they are 100 percent safe. The reality is we know some people will have adverse reactions even to ... properly prepared supplements."
Israelsen cited safeguards in the botanical regulatory system including AERs, warnings on labels when appropriate and notification to the FDA before new ingredients are introduced.
"No product for human consumption is 100% safe for all the people all of the time," he said in an emailed statement. "Consumers know this. The fact is dietary supplements enjoy a safe history of use, certainly as compared to drugs and some common foods."
Growing AERs in Industry
But FDA has received a growing number of supplement AERs in recent years. From 2008 through 2013, FDA received a total of 3,289 mandatory AERs connected to dietary supplements, or an average of 1,765 annually, according to figures FDA provided INSIDER last year. The numbers have increased from 687 in 2008 to 3,289 in 2013. (FDA did not immediately respond to a request for comment on the total numbers for 2014).
The data raises the question, but does not answer, whether there is an increasing number of dangerous natural products on the market. The growing numbers, supplements executives have argued, are actually a credit to the supplement industry because it demonstrates that it has become more compliant with a mandatory AER law: the Dietary Supplement and Nonprescription Drug Consumer Protection Act.
Public health officials have cited challenges in determining if an AER actually caused an illness. Consumers may provide incomplete medical information, complainants may not participate in a follow-up investigation, and pharmaceuticals, illegal drugs or other substances may adversely interact with a product.
Of the 6,037 supplement AERs FDA received from 2008 through 2011, the agency only established a "certain" relationship between the product and the reported health problem in 3 percent of the cases, according to the U.S. Government Accountability Office (GAO).
Editor’s Note: For information on adulteration in botanicals, attend Ingredient Marketplace, a SupplySide event held April 7 to 9. The event will feature the panel discussion “Adulteration & Your Role in Delivering Value to Consumers" on Wednesday, April 9 just before the show floor opens. This panel will help brands examine business practices and how to align them so they can truly offer valuable finished goods to shoppers. So far, speakers include American Botanical Council (ABC) founder Mark Blumenthal, Council for Responsible Nutrition (CRN) CEO Steve Mister, and Kleinfeld, Kaplan and Becker partner Dan Dwyer.