The death occurred in 2007, but the FDA did not learn of it until March, 2009, a delay that is not unusual given that supplement manufacturers are subject only to voluntary, not mandatory, reporting of adverse events. And, unlike drug manufacturers who must follow strict disclosure regulations regarding active ingredients, supplement manufacturers are not required to disclose precise ingredients to the FDA, but can hide behind the "proprietary blend" rubric. This makes it especially difficult for the agency to identify the toxic substances causing the adverse events. The FDA was unable to identify the precise substance believed to be at work here, but the pattern of injury suggests that adverse events may occur regardless of dosage or the length of use of the product.
The surprise here is not that untested diet supplements can cause hepatotoxicity, even at recommended doses, or that there is no free lunch in the world of weight loss supplements. The surprise is that Hydroxycut is still in business. Remember its tattered history of using ephedra in its products, using deceptive before and after photographs, and falsely claiming that it had scientific data of its product's effectiveness (when, in fact, study participants were dropping out due to adverse events and the company replaced them with new study participants). The surprise is that our current regulatory scheme has allowed the company to remain in business at all.
SOURCES:
FDA: News Release--5/1/09
Missouri AG: News Release--3/27/03; News Release--5/4/04
Medical Literature: Hydroxycut hepatotoxicity: A case series and review of liver toxicity from herbal weight loss supplements, World J Gastroenterol 2008 December 7; 14(45): 6999-7004; Hepatotoxicity associated with weight loss supplements: A case for better post-marketing surveillance; World J Gastroenterol 2009 April 14; 15(14): 1786-1787.
New York Times: Studies of Dietary Supplements Come Under Growing Scrutiny, 6/23/03
The FDA has warned that some of the supplements contained drugs far in excess of the maximum recommended dosage of the drug. The risks posed by these products include high blood pressure, seizures, tachycardia, palpitations, heart attack, or stroke.
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This opinion completes a trio of Court decisions on the preemption doctrine. The first, Riegel v. Medtronic, Inc. v. Good, established that state products liability suits were preempted by federal medical device regulations unless there were other FDA violations. The second, Altria Group, Inc. v. Good, established that state claims based on unfair trade practices could be asserted against cigarette manufacturers even though cigarette labeling is regulated by the FTC.
Today's decision in Wyeth v. Levine is an essential one because the FDA is not able to ascertain before marketing all the risks of a drug or errors in labeling. When there is negligence by the manufacturers, the safeguard of the courts is needed to protect consumers fully. If the FDA were the only safeguard in the system, and there were no checks-and-balances provided by the courts, consumers would unquestionably be at greater risk. There is no doubt that the Court's decision today was the correct one.
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The GAO ticked off the items we know already: that the FDA should request more power from Congress to regulate the diet supplement industry, that the FDA can't require that a company remove tainted supplements from the marketplace, that the public does not know there has been no testing of the products for safety and efficacy, and that manufacturers should register with the FDA and disclose the specific supplements and ingredients to the agency. We certainly know that "consumers remain vulnerable to risks posed by potentially unsafe products."
Key Events in the Regulation of Dietary Supplements
1990
The Nutrition Labeling and Education Act of 1990 amended the Federal Food, Drug, and Cosmetic Act to require most foods, including dietary supplements, to bear nutrition labeling.
1994
DSHEA amended the Federal Food, Drug, and Cosmetic Act to create a new regulatory category, safety standard, labeling requirements, and other rules for dietary supplements. Under DSHEA, dietary supplements are generally presumed to be safe.
2002
The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 amended the Federal Food, Drug, and Cosmetic Act to require all food companies, including dietary supplement companies, to register with FDA no later than December 12, 2003, to provide information on the name and address of the facility and, to some extent, the types of products they manufacture or sell.
2004
FDA was successful in banning ephedra after thousands of adverse events, including a number of deaths, and a lengthy legal process.
2006
The Dietary Supplement and Nonprescription Drug Consumer Protection Act amended the Federal Food, Drug, and Cosmetic Act to require dietary supplement companies that receive a serious adverse event report to submit information about the event to FDA.
2007
FDA finalized its Current Good Manufacturing Practice regulations to establish quality control standards for dietary supplements. The final rule became effective on August 24, 2007, but companies have 10, 22, or 34 months from the effective date of the rule to comply, depending on company size.
2007
Serious adverse event reporting requirements for dietary supplement companies became effective on December 22.
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The litigation was filed in 2007, and accused Mannatech of using an illegal marketing scheme to defraud consumers Mannatech markets supplements called "glyconutrients" that supposedly provide the body with "essential sugars" that promote "better communication" between cells and support the immune system. Leading scientists are critical of the company's theory of "glycobiology," and one was prompted to characterize the product as literally, a sugar pill (well known in science as a placebo with no active ingredients).
Still pending is the litigation against three other defendants named in the litigation, H. Reginald McDaniel, a Mansfield physician who has been long associated with the company, and two charitable organizations tied to the company, MannaRelief Ministries and Fisher Institute for Medical Research. The litigation accused them of violating the Texas Deceptive Trade Practices Act and the Texas Food, Drug and Cosmetic Act.
We often look to the FDA to regulate this industry, and forget the excellent work done by state agencies. Remember, it was the Texas FDA that began the work against the dangerous marketing of ephedra, which the FDA later took over. In the past, state agencies in California, New York and Florida have also taken strong positions against dangerous or deceptively marketed supplements. The fundamental problem, however, is that we cannot rely on state-by-state regulation; the problem requires a federal solution. Only a few states are large enough to fund their state FDA adequately or support litigation efforts like those of the Texas AG. (And then there is Utah, where the diet supplement industry is treated like a state-sponsored drug cartel.) While we must encourage the efforts of states like Texas, the states should not be left to clean up the industry themselves. The fact that Texas had to bring the litigation at all speaks volumes about the larceny DSHEA permits and the harm that has come from the FDA's inaction. The FDA should be handling these problems with a consistent and unrelenting regulatory effort, and Congress should amend DSHEA to permit the FDA to do its job.
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Benchmark: Litigation has released its 2009 rankings, as well. Reprising its 2008 listing by the organization, Atkinson, Conway & Gagnon was again listed as one of five law firms in Alaska selected for its premier "highly recommended" listing.
Both organizations utilize peer review surveys of practicing lawyers as an independent and objective means of determining which law firms are regarded by their peers as performing exceptional legal work.
]]>Imagine for a moment that it has been discovered that Pfizer had "spiked" its new blockbuster drug with a different, undisclosed drug, (or for that matter a diet supplement!). The FDA and the industry would be embroiled in immediate inquiries, and heads would roll. On the other hand, the FDA has known for decades about the illegal "spiking" of diet supplements with pharmaceuticals and has simply let the matter fester.
Be that as it may, the FDA has now released warnings as to a number of supplements, and has indicated that it will be seeking recalls of some of them. The supplements were found to contain sibutramine (a controlled substance), rimonabant (a drug not approved for marketing in the United States), phenytoin (an anti-seizure medication), phenolphthalein (a solution used in chemical experiments and a suspected cancer causing agent) or bumetanide (a diuretic). These substances all have pharmaceutical properties that include the laundry list of adverse effects one would expect. We have previously written about the deadly consequences of this type of adulteration here, and here, and we commend the agency for its efforts. Regardless whether the FDA is getting it or just getting around to it, this heightened scrutiny is long overdue.
Sources:
New York Times, February 9, 2009
]]>A co-defendant, Sergio Oliveira, a sales associate, was sentenced to 20 months in prison and fined $20,000. The judge had previously sentenced two other Hi-Tech officials, Stephen D. Smith and Tomasz Holda, to 27 months and 16 1/2 months respectively.
Hi-Tech’s supplements include Stamina-Rx, which it claims to be a "maximum sexual stimulant," Lipodrene, supposedly capable of "advanced appetite control and metabolic stimulation," and Metanabol, marketed as a "revolutionary catalyst for increasing lean mass and strength."
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A new report by the FDA asks the simple question whether the FDA is up to the challenge of regulating engineered nanoparticles in diet supplements. Without reading the report, we know the answer to be "no." The FDA is not set up to litigate, it has not been given a true mandate to regulate this industry, it is underfunded, and its scientists are squelched. But let's see what they say. "It is not clear that the supplement industry is conducting the rigorous testing needed either to understand the effects of nanoscale ingredients in its products or to back up product claims." We had to pay for a study to get to this conclusion? The industry doesn't do "rigorous testing". It doesn't on anything it sells, because it isn't legally required to do so. Instead, the industry does "rigorous marketing".
As for whether the agency is "up to the challenge," the report concludes: "The short answer is no." Three reasons are given: 1.) the agency doesn't have the capacity to identify nano-based supplements; 2.) the agency has little regulatory authority over such supplements; and 3.) the agency lacks the scientific expertise and resources to effectively regulate these supplements. The report recommends what has been obvious for decades now--increase the agency's regulatory authority, and increase its resources.
The report provides a summary of the regulatory history that brings us to the current DMZ of DSHEA, and it even tackles summarizing the regulatory efforts aimed at corralling ephedra. It provides a disturbing summary of the increased budget and mandate of the agency in inverse proportions to the number of agency employees expected to accomplish the agency's goals.
Ultimately, the report recommends that rational steps be taken, such as product registration, safety standards, market review, pre-market testing, adverse events reporting, and increased resources.
The report's appendix contains a list of over 40 supplements using nanoparticles, but it does not articulate the safety risks the consumer faces. These risks include not only the direct risk to consumers, but also to those manufacturing the products, and the risk to the water supply, the environment, and animals.
One has to appreciate the efforts of the agency to articulate this nano-concern, but the report merely states the obvious as to the flagrant regulatory gaps that have been with us for decades now. The agency has to step up to the plate, as does Congress. The Obama administration's stated goals suggest a new direction for the agency, and a return to science and consumer-based regulatory purposes. This will require that America step back from the gluttony of unbridled capitalism and the ritualistic zeal of woo. Perhaps we can, but I wouldn't bet on it.
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]]>The scientists further detailed their efforts to take their concerns to agency leaders, such as Commissioner Andrew Von Eschenbach, and the assistant commissioner for accountability and integrity, attorney Bill McConagha, but no changes have occurred. Worse yet, the problematic managers were not held accountable, but were promoted and rewarded.
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To date, the FDA has received 2,250 reports of tendon disorders and 775 reports of tendon ruptures. The problems have arisen in the Achilles' tendon, as well as shoulder, hand, and other tendons. These numbers are only a small percentage of the adverse events that have likely occurred because adverse events are routinely underreported. The risk is higher in patients older than 60, and in those taking corticosteriods.
One concern about the increase in this complication is the increased use of this class of antibiotic, one some refer to as "Vitamin L". It is apparently widely prescribed because it addresses a wide spectrum of bacteria, but the marketing of the drug characteristically underinforms doctors about this type of complication.
This type of adverse event adds to the reasons to question a doctor's prescription of antibiotics, such as toxcity, cost, and creating antibiotic resistant bacteria. If the benefits truly outweigh the risks, the patient should be informed about these potential complications:
Tendon Disorders: Watch for pain, swelling or inflammation.
Heart Problems: Watch for heart rhythm problems.
Dangerous Diarrhea: Watch for persistent or watery diarrhea, sometimes long after use.
Nerve Problems: Watch for numbness, weakness, burning, and tingling.
Others: Seizures, hallucinations, depression, light sensitivity, damage to liver, kidney or bone marrow, and changes in blood sugar.
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The case arose in Maine and asserted that the company had fraudulently misrepresented that its "light" cigarettes were safer. Essentially, today's ruling refuses to immunize fraudulent statements by corporations and has reaffirmed the presumption in the law against preemption of state laws: "When addressing questions of express or implied preemption, we begin our analysis with the assumption that the historic police powers of the States are not to be superseded by the Federal Act unless that was the clear and manifest purpose of Congress." "Thus," it continues, "when the text of a pre-emption clause is susceptible of more than one plausible reading, courts ordinarily accept the reading that disfavors preemption."
Sources:
Atria Group v. Good (pdf of opinion)
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