In the 20 years since Congress passed the 1994 Dietary Supplement Health and Education Act (DSHEA), FDA has rarely invoked its administrative rulemaking authority to ban natural products that have been associated with health hazards. Loren Israelsen, president of the United Natural Products Alliance (UNPA) can only recall one instance in which FDA removed supplements from the market under DSHEA based on a finding that the products posed “a significant or unreasonable risk of illness or injury." That was in 2004 after products containing ephedra were linked to adverse health outcomes, such as heart attack and stroke.
A consumer interest group—and others including Israelsen—contend FDA has the authority to take similar action in the wake of at least two recent deaths that have been blamed on powdered caffeine.
Petition to ban bulk caffeine
In December, the Center for Science in the Public Interest (CSPI) petitioned FDA to ban the retail distribution of pure, powdered or liquid caffeine as a dietary supplement. Lawmakers who met with the parents of a teenager who died after ingesting powdered caffeine have urged FDA to enact the ban.
“Given that very small amounts of powdered caffeine can cause severe adverse events including death, it is time for the FDA to use its authority to ban the sale and marketing of this dangerous product," six senators wrote in a Jan. 22 letter to FDA Commissioner Margaret Hamburg.
An FDA official, Thomas Kraus, advised Sen. Richard Blumenthal (D-Connecticut) in a March 16 letter that “the Agency is committed to addressing this important public health issue and continues to evaluate the complex legal, scientific, and policy issues associated with bulk powdered caffeine products."
While FDA has opened a docket on CSPI’s petition, and is normally given 180 days to act, the request could linger for years. Laura MacCleery, chief regulatory affairs attorney for CSPI, said some petitions that have been filed with FDA have been pending for decades. The consumer group isn’t likely to sue the agency in federal court for failure to take action until such a petition has been sitting at the agency for at least a few years. That’s because the courts have generally ruled lawsuits that immediately challenge FDA’s failure to act have been filed prematurely, MacCleery said.
“We are going to be pressing FDA [on the caffeine petition] in the meantime," she said in a phone interview.
CSPI requested FDA find pure caffeine as a dietary supplement poses “a significant or unreasonable risk of illness or injury under conditions of use suggested or recommended in the labeling," or in the absence of the aforementioned findings, “under conditions of ordinary use." The language comes out of DSHEA and comprises an amendment to the 1938 Federal Food, Drug & Cosmetic Act (FD&C), which defines adulterated or unsafe foods.
“Just as FDA removed ephedra from the market under authority granted by DSHEA, that option is open to FDA," said Israelsen, who sat on FDA's Expert Advisory Committee on Ephedra. “I don’t know what they will do. We feel FDA has authority."
Complications for regulators
Whether FDA would invest the legal and scientific capital to seek a ban on pure caffeine remains an open question. Vasilios (Bill) Frankos, Ph.D., a former FDA official and current Herbalife Ltd. executive, cited “enormous" manpower that FDA invested over a period of years to compile the administrative record in support of the ephedra ban—not to mention years of litigation challenging FDA in the courts. Frankos, then an FDA senior science advisor, was not involved with the ephedra ban, but he went on to become director of FDA’s Division of Dietary Supplement Programs before joining Herbalife in 2010.
“The burden to show a significant risk … is much higher than the normal standards that are used by FDA to allow the marketing of a dietary supplement, which is basically showing there is no harm and that product has what is called ‘a history of safe use,’" said Frankos, Herbalife’s senior vice president of global regulatory compliance and product safety, in a phone interview.
He predicted such a ban would face challenges in court.
Although seasoned lawyer Scott Bass of Sidley Austin LLP agreed FDA has the authority to make a finding that powdered caffeine presents an unreasonable risk of illness or injury, he said he learned through numerous sources that FDA believes it may be more difficult to ban the product because caffeine has been generally recognized as safe (GRAS) for certain food uses.
Frankos agreed that marketing powdered caffeine as a food could complicate attempts to ban it. Although FDA said as recently as last year that it was continuing to study safe levels of caffeine consumption in the wake of deaths potentially tied to caffeinated energy products, caffeine has been extensively researched and is reportedly the most widely used drug in the world.
“Unless the ingredient is labeled as a dietary supplement, you really can’t go after it using the significant risk provisions," Frankos said. “The way in which it’s being marketed may not be a supplement. It could be just a food ingredient going into common foods and beverages, and therefore you really can’t go after it unless it’s actually labeled in a way that could cause it to be considered harmful."
FDA could argue powdered caffeine sold in bulk bags was dangerous, even if it wasn’t labeled as a supplement. For instance, Bass pointed out the 77-year-old FD&C defines a food as adulterated if it “bears or contains any poisonous or deleterious substance which may render it injurious to health."
Frankos also said there may be ways for FDA to restrict the manner in which powdered caffeine is sold, such as ensuring only a safe amount is dispensed at one time by placing caps on powder samples. FDA has specifically raised concerns about powdered pure caffeine that is being marketed to consumers in bulk bags over the Internet.
Dangers of bulk caffeine
The problem with powdered caffeine is striking—there is a “very small" difference between an amount of powdered pure caffeine that is considered safe and one that is fatal, according to an FDA consumer warning discouraging consumption of the product. A single teaspoon of pure caffeine is roughly equivalent to the amount of caffeine in 25 cups of coffee, according to FDA.
Last week, three supplement trade groups including UNPA, Council for Responsible Nutrition (CRN) and American Herbal Products Association (AHPA) announced policies and guidelines that discourage the sales of powdered caffeine to consumers by their members in the wake of at least two fatalities that have been tied to the product.
Steve Mister, president and CEO of CRN, said consumers don’t typically have the measuring tools to calculate a safe quantity of powdered caffeine.
The widespread availability of caffeine powder may give consumers little reason to think it’s potentially deadly. The parents of Wade Sweatt, a 24-year-old Georgia resident whose death was linked to ingesting caffeine powder, said their son purchased it from Hard Rhino on Amazon.com. He was a newlywed and recent graduate of the University of Alabama at Birmingham, FDA official Michael Landa, now retired, wrote last year in a blog that emphasized the dangers of powdered pure caffeine.
“The very first time he ever used the product, he mistakenly took too much, and it killed him," the Sweatts said in a statement attached to CSPI’s citizen petition. “Why would such a dangerous product be allowed to be sold to individuals?"
Last month, a lawsuit was filed in Ohio state court against Amazon, Hard Rhino and affiliated companies in connection with the death of Logan Stiner, an 18-year-old who died on May 27, 2014, just three days before his high school graduation. The teenager was a student-athlete who planned to attend the University of Toledo, volunteered with the Special Olympics and was a member of the National Honor Society, according to the Logan Stiner Foundation.
The coroner cited Logan’s cause of death as “cardiac arrhythmia and seizure due to acute caffeine toxicity due to excessive caffeine ingestion," according to the lawsuit.
Amazon, its counsel and Hard Rhino did not respond to requests for comment.
In December, FDA officials met with the parents of Stiner and Sweatt. Landa, who was then director of FDA’s Center for Food Safety and Applied Nutrition (CFSAN), encouraged consumers to avoid using powdered pure caffeine.
“The people most drawn to it are our children, teenagers and young adults, especially students who want to work longer to study, athletes who want to improve their performance, and others who want to lose weight," he wrote.
In an emailed statement on CSPI’s petition to ban powdered caffeine, FDA spokeswoman Siobhan DeLancey said the agency is still evaluating its “position and [has] not yet made a determination regarding our options, but we are very pleased and supportive of the statements that CRN and others have made regarding their membership."
Brian Balser, an Ohio lawyer representing Stiner’s estate, argued in the 52-page lawsuit that the “Defendants have successfully avoided meaningful regulation of its product by the U.S. Food and Drug Administration … by classifying their product as a ‘dietary supplement.’" (Natural Products Insider reached out to Balser for written comments or a phone interview with the Stiner family, but he declined to comment).
It was more than a decade ago after ephedra-containing supplements were potentially linked to scores of illnesses and fatalities—including the death of Baltimore Orioles rookie Steve Bechler—that FDA banned the products through an administrative rulemaking proceeding.
In issuing the final rule banning ephedra on Feb. 6, 2004, FDA said it found ephedra products “present an unreasonable risk of illness or injury." Before reaching its conclusion, the agency revealed its effort was a huge undertaking.
FDA evaluated ephedra's pharmacology, peer-reviewed scientific literature on ephedra's safety and effectiveness, adverse event reports (AERs) and a report by an independent scientific institute. The agency also reviewed tens of thousands of pages of comments in connection with its request for information on ephedra-related health risks.
Soon after FDA made its decision, the litigation commenced. As The Washington Post reported, a federal judge in April 2005 struck down the ban, ruling in favor of Nutraceutical International Corp., which argued ephedra had been safely consumed for hundreds of years. More than a year later, a federal appeals court upheld FDA’s ban.
The case is illustrative of the dangers of overreliance on unsubstantiated reports that potentially link a product to a death or illness. Of the hundreds of serious AERs linked to ephedra that the expert panel reviewed, a “huge percent of those were disqualified for further consideration," said Israelsen, who served on the panel as industry liaison. “The facts weren’t there. The facts were inconsistent."
Israelsen, who has been involved in commercial and regulatory issues facing the dietary supplement industry since 1980, said there was probably only around a dozen instances where one could “make a fairly clear association between the consumption of ephedra and the injury."
Other FDA tools
In more recent times, FDA has invoked the “unreasonable risk of illness or injury" language. Daniel Fabricant, Ph.D., former supplement director at FDA, said the agency did so in a 2013 letter that was sent to USPlabs in the wake of a hepatitis outbreak. In that letter, FDA gave USPlabs 48 hours to voluntarily recall OxyElite Pro, and the company complied with the request, added Fabricant, who presently serves as executive director and CEO of the Natural Products Association (NPA).
Fabricant said FDA had issued the letter to USPlabs based on its mandatory recall authority granted to it under the now 4-year-old Food Safety Modernization Act (FSMA). The federal Centers for Disease Control and Prevention (CDC) indicated the fat-burning supplements may have adversely affected nearly 100 people in more than a dozen states.
But the USPlabs case also underscored the painstaking back-and-forth that can go on between industry and government, even when regulators suspect that a product is responsible for illness and/or death. In an interview last December with the Dallas Morning News, USPlabs’ outside counsel Peter Barton Hutt said USPlabs “strongly believes" the precise cause of the Hawaii outbreak has not yet been identified.
It’s also theoretically possible, though, unlikely that FDA would move to restrict powdered caffeine sold in bulk bags based on a separate provision of DSHEA. The Secretary of the U.S. Department of Health and Human Services (HHS) has authority to find that a supplement is adulterated if the Secretary declares that a product poses “an imminent hazard to public health or safety." Regulatory experts said that provision has never been invoked.
Bass, who heads Sidley Austin’s global Life Sciences team and whose supplement clients have included such heavyweights as Bayer Corp. and Herbalife, said former FDA commissioner David Kessler declined to invoke the provision in the ephedra cases.
“He was so angry about DSHEA, he said ‘my hands are tied,’" Bass said. “I remember saying to him that is a good publicity move, but you are really disserving the industry."
Kessler, a Harvard Medical School-educated doctor who also obtained a law degree from University of Chicago, left FDA in early 1997, seven years before ephedra was banned from the market. But as far back as 1996 under Kessler’s leadership, FDA warned consumers against buying dietary supplements containing ephedra.
"These are recreational street drugs masquerading as dietary supplements," Kessler said in an interview with the Los Angeles Times. "This new class of street drugs has emerged and we needed to focus attention on them. These are drugs and should be regulated as such."
In 2004 testimony on dietary supplement safety before a Senate government subcommittee, a representative of Consumers Union quoted Kessler as saying, “Congress put the FDA in the position of being able to act only after the fact and after substantial harm has already occurred."
Judiciary and voluntary recalls
With the exception of the HHS provision and absent a rulemaking procedure such as occurred in the ephedra debacle, FDA must go to court with the aid of the U.S. Justice Department to enforce a provision under DSHEA, Bass said.
Even an administrative rulemaking that banned a product is likely to face challenges in federal court, as Frankos pointed out.
Mister declared FDA’s rare use of its authority under DSHEA to ban products from the market doesn’t mean the agency doesn’t have the ability or tools to protect the public health “because FDA is able to go in, cajole and persuade the company with the recall."
He cited as an example the voluntary recall of Hydroxycut products from the market after they were linked to health problems such as jaundice, liver damage and seizures.
Parents who blame powdered caffeine for taking the lives of their children are probably less concerned with the logistics—just that the product is removed from the market.
"Before May 27, 2014, we had never heard of 'caffeine powder,'" said Katie Stiner, Logan’s mom, in a statement issued last year by CSPI. "Now we think about it every day. We decided that we must do everything we can to get this product off the market and away from other children."