Regulatory roulette

Abstract

Part 2 of a 3-part series regarding the debate over how herbal supplements are researched, regulated, and investigated. At its heart, the debate over herbal supplements often comes down to this: should a sprawling category of products that includes everything from weight loss pills to crushed herb teas be regulated as foods or medicines? In 1994, the US Dietary Supplement Health and Education Act classifi ed herbal products as the former, freeing them from the US Food and Drug Administration's (FDA) more stringent oversight of drugs. As foods, they would not have to demonstrate efficacy, only a reasonable expectation of safety when used as recommended or suggested. The industry mushroomed. Sales skyrocketed. And fierce debates over whether the US public has been well served by the regulatory detente have fl ared ever since. In a 2014 speech, Senator Orrin Hatch (R-Utah), 1 of the law's chief architects, called it a “remarkable achievement.” In a 2016 perspective piece, Donald Marcus, MD, professor emeritus of medicine and immunology at Baylor College of Medicine in Houston, Texas, instead called it “arguably the worst health care legislative act of the twentieth century.”1 Most other opinions have fallen between these 2, although multiple supporters and detractors interviewed by CytoSource largely agreed on 1 point: the federal government's current regulatory strategy is not working. “It's a mess,” says Anna-Marija Helt, PhD, a clinical herbalist in Durango, Colorado, with a background in cancer research. Ms. Helt likes the community herbalist model and bristles at the notion of licensing restrictions regarding who can join her profession. She also objects to what she views as scare tactics used by opponents to characterize all herbal supplements. “But at the same time, yes, I understand that it is kind of the Wild West,” she says. “People are allowed to buy whatever supplements they want, and there are a lot of garbage supplements out there.” Other products, she acknowledges, can have legitimately bad interactions. “How do you regulate access to that? It's a tricky question.” In fact, the lack of regulations and safeguards such as practitioner insurance can make her profession riskier. “It makes you really careful about what you do,” she says. Ms. Helt avoids herbs with known toxicity and makes her own tinctures and teas from plants she has grown herself or gathered or bought from reputable suppliers. “There are certain parts of the world I will not buy herbs from because they are notoriously adulterated,” she says. There is good reason for caution. In a 2014 opinion piece, Pieter Cohen, MD, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, argued that the Dietary Supplement Health and Education Act law fl ips the burden of proof so that “anything labeled as a dietary supplement is assumed to be safe until proven otherwise.”2 When his own peer-reviewed research suggested that some dietary products marketed as natural weight loss supplements actually contained an illegal and potentially dangerous amphetaminelike synthetic compound, Dr. Cohen was sued–unsuccessfully–by the supplement's manufacturer for libel and slander. Dr. Cohen declined to be interviewed by CytoSource, but a special report by STAT in January 2017 revealed that 6 of the supplement brands implicated by his research remain on the market, despite an ordered recall by the FDA.3 “We have a great deal of respect for Dr. Cohen and his research,” says Steve Mister, president and Chief Executive Officer of the Council for Respon-sible Nutrition, a trade association and lobbying group based in Washington, DC. Mr. Mister questions some of the policy conclusions stemming from that research, but he says the association supports Dr. Cohen's “watchdog” efforts to identify products that should not be sold as supplements. Mr. Mister contends that the 1994 law and later additions have given the FDA “ample opportunities to intercede and prevent dangerous products from getting to market.” The problem, he says, is insufficient enforcement. “It's sort of like setting the speed limit at 55 and then you never have a cop on the road and people know it,” he says. “Drivers will speed.” The industry association, Mr. Mister says, has regularly lobbied both Congress and the FDA to make more resources available and to use its existing enforcement tools. “The notion of giving companies a warning letter and 6 months later, the product is still in the marketplace? That's not good for my members who are making good product, and it's certainly not good for consumers,” he says. Perhaps nowhere is the regulatory morass more apparent than in the patchwork and contradictory approach to kratom, an evergreen tree with a long history in Southeast Asia as a traditional medicine for pain and mood disorders. In the United States, the herb has grown in popularity as an opioid substitute. In 2016, a brief report from the US Centers for Disease Control and Prevention labeled the herb an “emerging public health threat” based on a 10-fold spike in kratom-related calls to poison control centers from 2010 to 2015.4 Oliver Grundmann, PhD, clinical associate professor of medicinal chemistry at the University of Florida in Gainesville, points out that the study and others like it have not been able to definitively answer whether the reported deaths are attributable to kratom alone. “In all cases, there were other substances that were used,” he says. “It may have been alcohol, it might have been opioids, it might have been antidepressants.” Nevertheless, the Centers for Disease Control and Prevention's report caught the attention of the FDA and the Drug Enforcement Agency (DEA). “As soon as you mention ‘opioid’ to the DEA, the alarm bells ring, and they think of yet another substance that adds to the already existing opioid crisis,” Dr. Grundmann says. Beyond combing through the available literature to gauge the risks of individual supplements, Dr. Leonard says she often must assess whether a supplement manufacturer's list of ingredients can be trusted. The DEA initiated plans to ban kratom and its 2 main alkaloid compounds before an outcry from patients and other advocates prompted the agency to halt the ban, at least until the FDA could gather more data. However, as of February 2017, the herb had been banned in 6 states and Florida's Sarasota County, with several other bills to ban the supplement pending. Preliminary research has suggested that kratom's alkaloids may interact with the brain's opioid receptors, perhaps through a different pathway than morphine or oxycodone. However, given the herb's uncertain regulatory future, Dr. Grundmann says the scientific community has been reluctant to apply for research funding to study it. Dr. Grundmann says that the uneven regulatory framework also means that anyone can offer advice on benefits and risks without any consistent evaluation of the information's reliability. “What remains at this point is the consumers informing themselves, basically,” he says. “That puts a lot of the burden on average folks.” It also places a burden on physicians. Institutions such as the Mayo Clinic, Cleveland Clinic, and Consumer Reports have periodically weighed in on the effi- cacy, safety, and drug interactions of herbs. None have been immune from criticism, either for being insufficient or overly critical in their analysis. Mandy Leonard, PharmD, a pharmacy system director and drug information specialist at the Cleveland Clinic, says she uses sources such as the Natural Medicines Comprehensive Database (compiled by Therapeutic Research Center in Stockton, Calif) and the National Institutes of Health Office of Dietary Supplements. The National Institutes of Health office, in turn, relies in large part on fact sheets prepared by the controversial National Center for Complementary and Integrative Health, which has been criticized as being overly friendly to alternative therapies. For acai, first on the center's list of 52 common herbs, its Web site asserts, “There's no definitive scientific evidence based on studies in people to support the use of acai for any health-related purpose.” The US Federal Trade Commission even lodged legal complaints and issued scam alerts in 2011 over fake news sites promoting phony claims that acai-containing supplements could yield dramatic weight loss. The commission issued another consumer alert in 2014, warning of “free” introductory offers that were anything but free. Three years later, these actions have done little to deter marketers. A recent Google search revealed dozens of acaicontaining teas, tinctures, pills, powders, capsules, and chews sold as weight loss supplements, many of which promise results in just days or weeks. In her talks with patients and their caregivers, Dr. Leonard says she has adopted a “buyer beware” approach and underscored the importance of telling providers what patients are taking. That information, however, only goes so far. Beyond combing through the available literature to gauge the risks of individual supplements, Dr. Leonard says she often must assess whether a supplement manufacturer's list of ingredients can be trusted. Her task has been all but impossible when companies have refused to divulge their “propriety blend” of supplements. “Well, then I've got to tell the patient not to do it,” she says, “because I have no idea what's in it.”