Herbal diet supplement found to have amphetamines that were not disclosed..Sheesh!..this came from Mayo Clinic Proceedings..
Amphetamine Lacing of an Internet-Marketed Neutraceutical
MINH H. NGUYEN, MD; TOM ORMISTON, MD; SANJAY KURANI, MD; DENISE K. WOO, MD
From the Department of Internal Medicine, Santa Clara Valley Medical Center, San Jose, Calif (M.H.N., T.O., S.K.); and Department of Health Research and Policy, Stanford University, Palo Alto, Calif (D.K.W.).
Individual reprints of this article are not available. Address correspondence to Minh H. Nguyen, MD, Department of Internal Medicine, Santa Clara Valley Medical Center, 751 S Bascom Ave, San Jose, CA 95128 (e-mail: Minh.Nguyen1@hhs.co.santa-clara.ca.us).
Abstract
A 25-year-old woman presented with abdominal pain after taking an imported herbal weight-loss product. A urinary toxicology screen was positive for amphetamine, which the patient denied taking. On further investigation, the neutraceutical was found to contain an amphetamine derivative banned by the US Food and Drug Administration (FDA). Although the patient had discontinued use of the supplement before hospitalization and her symptoms steadily improved with appropriate treatment, a report was made to the FDA. Similar reports from cities across the United States prompted the FDA to confiscate shipments of the product before it could be distributed further nationally while they investigate claims against the product.
Mayo Clin Proc. 2006;81(12):1627-1629
DSHEA=Dietary Supplement Health and Education Act of 1994; FDA=Food and Drug Administration
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People often use herbal supplements because they believe that they are naturally derived and hence safer than many other consumable products.1 Advertisements for supplements sometimes push the boundaries of the Dietary Supplement Health and Education Act of 1994 (DSHEA) by claiming usually unsubstantiated medical effects. Given the large number of neutraceutical products available, the minimal evaluation of their pharmacology, and limited US Food and Drug Administration (FDA) oversight of substances marketed as neutraceuticals, it is not surprising that adverse effects can occur, either from unknown properties of the neutraceutical components or possibly lacing of the mixtures with unlabeled ingredients. We describe a patient who was exposed to amphetamine when taking what she believed was an herbal supplement for weight loss.
REPORT OF A CASE
A 25-year-old woman presented to the emergency department with persistent, increasingly severe abdominal pain of 2 weeks’ duration and a 1-day history of nausea and vomiting. Her medications included high-dose ibuprofen, which had been discontinued 5 days before presentation, and a Brazilian weight-loss supplement, Emagrece Sim (purchased on the Internet from www.emagrece-sim.com), which she had discontinued 2 weeks previously. The patient reported that she had had palpitations and felt mildly tremulous after taking the supplement. Friends who were also taking the supplement had experienced similar uncomfortable excitability. She denied having chest pain or shortness of breath. The abdominal pain was described as dull and midepigastric with a sharper quality at various times. The patient had been evaluated twice by physicians as an outpatient during the previous 2 weeks, and gastroesophageal reflux disease had been diagnosed. Initial treatment with ranitidine was switched to pantoprazole at her second office visit. Neither treatment provided improvement. On presentation to the emergency department, the patient’s vital signs were stable; her heart rate was mildly elevated above baseline at 88 beats/min. She appeared to be in mild discomfort. Physical examination findings were notable only for an obese abdomen with diffuse, mild tenderness and hypoactive bowel sounds.
On admission to the hospital, results of routine blood analysis for electrolytes, complete blood cell count, amylase, lipase, and liver function were within normal limits. Abdominal x-rays and noncontrast computed tomography revealed no pathology. Esophagogastroduodenoscopy showed a normal esophagus and stomach. A urinary toxicology examination was positive for amphetamine. On further questioning, the patient admitted that she had tried cocaine several years previously and had used marijuana within the past several months, but she denied amphetamine use. She suspected that the amphetamine detected in her urine was associated with a new Brazilian diet supplement she had been taking. She and some of her friends had individually lost up to 2.25 kg in 1 month. She stated that she had stopped taking the supplement 2 weeks previously only because the cost of $270 for a 1-month supply was not affordable on her limited income.
Some bright yellow and orange diet capsules (Figure 1) were brought to the hospital by one of the patient’s friends for further analysis. The contents of the diet capsule, which on visual inspection appeared to contain herbal ingredients, were mixed with sterile water. Gas chromatographic and mass spectrometric analysis of the supernatant in the local hospital’s toxicology laboratory confirmed the presence of 5-cyanoethyl-amphetamine, an amphetamine derivative used outside of the United States for weight loss but deemed illegal by the FDA.
The product’s Web site (www.emagrece-sim.com) listed kava kava, Gingko biloba, and other herbal ingredients, but no mention was made of an amphetamine component. The Web site indicated that the special blend for the neutraceutical was created in Brazil but shipped to Miami for distribution in the United States. On further interview, the patient revealed that the product had been purchased legally from the Internet and delivered to the homes of at least 6 of her friends by the US Postal Service.
FIGURE 1. The contents of the diet capsule appear to contain herbal ingredients.
The patient was treated with metoclopramide (10 mg orally every 8 hours), pantoprazole (40 mg/d orally), and acetaminophen (650 mg orally every 6 hours as needed for pain). She was discharged from the hospital 3 days later when her symptoms had subsided. She was instructed to not resume use of the supplement. Although the patient agreed, she stated that several of her friends were using the supplement to lose weight. None of them had experienced abdominal pain, and she did not believe that all of them would stop using the supplement. At her follow-up appointment 1 week after hospital dismissal, the patient was pain free, and the metoclopramide was discontinued. Her friends continued to use the amphetamine-containing neutraceutical despite warnings, mostly because of its effectiveness for weight loss.
A report was placed on MedWatch at the FDA Web site (www.fda.gov/medwatch), and a follow-up telephone call was placed to the local FDA office. Our analysis of the diet supplement and a report of the harmful effects experienced by our patient were provided to the local FDA agent, who initiated an investigation. Because a sample bottle of the supplement was not available, the agent was directed to www.emagrece-sim.com, the Web site from which the patient had bought her supply. The agent was able to make multiple purchases of the product for further testing. The FDA agent requested an interview with the patient, and after obtaining her permission, a meeting was arranged through our hospital’s social services department.
The patient remained pain free and healthy at 3-month follow-up. By that time, her friends were unable to obtain refills of the neutraceutical because the FDA had interrupted their supply. Later follow-up with the local FDA agent revealed that reports regarding this supplement had arisen in other locales and that the case was still open. Our most recent inquiry to the FDA indicated that although 3 shipments (a total 2666 bottles) of the supplement had entered the US market, the fourth and largest shipment of 1638 bottles was confiscated and is being warehoused while the FDA continues to investigate claims against the product (E. Anderson, oral communication, January 20, 2006).
DISCUSSION
In the United States, amphetamines and their derivatives have often been used for weight loss, both legally and illegally, and mild gastroparetic abdominal pain has been described with their use.2 Mild tachycardia and palpitations, as seen in our patient, also are characteristic of amphetamine use, but our patient did not have the hypertension, pupillary dilation, chest pain, and shortness of breath that can be associated with amphetamine abuse. Although our patient did not have all the classic signs and symptoms of amphetamine toxicity, failure of traditional treatments for dyspepsia necessitated further investigation of her constellation of seemingly unconnected complaints.
Because other people in the community were using the supplement, public health concern warranted analysis of the diet capsules. Although extensive testing of the product could have been done at a government laboratory, testing at our local hospital provided both timely and important information that allowed initiation of an investigation into the product and appropriate treatment of the patient. Since the amphetamine derivative we identified in the supplement was not available in the United States, the patient’s report of a foreign origin was validated, and we reported the incident to the FDA.
The FDA monitors adverse effects of licensed medications and supplements through MedWatch, the adverse reaction reporting service.3 However, surveys show that only 10% of adverse reactions to herbal supplements are actually reported.4 With poor compliance in reporting, the FDA’s job of regulating supplements is additionally difficult. Fortunately, most cases reported through local hospital reporting systems are usually routed to the FDA as well.
As designated in the DSHEA, the FDA regulates herbal supplements produced in the United States and oversees them for safety.5 With the expansion of the Internet, patients are increasingly exposed to the international nutritional supplement market in which the products are not subject to the basic quality controls required by the DSHEA.6 Although the FDA has a mandate to ensure dietary supplement safety,7 the safety of imported supplements cannot be ensured. Even Web sites that have abundant and clear English slogans (eg, the one accessed by our patient) often ship medications that have few English instructions or lists of ingredients. The accuracy of the ingredient lists of the products is often unverifiable. The manufacturer of the supplement taken by our patient had been investigated in the past, and 8 of its other products have been banned by the FDA.8 However, without regulations in place to verify the content of future products marketed by the manufacturer, Emagrece Sim could be sold through the Internet and delivered via postal service without testing.
With approximately 12% of Americans using herbal supplements,9 neutraceuticals are a major growing public health concern. The first step in diagnosing illness related to the use of supplements is awareness of the prevalence of herbal supplement use and asking patients about such use. Shortly after this case was discovered in San Jose, Calif, additional reports of the presence of amphetamine in Emagrece Sim appeared in the local lay press from cities throughout the United States, from Los Angeles to Philadelphia to Miami, and a national story appeared on CNN (Cable News Network).8 In these other cases, reports were made after positive drug screen results were obtained during employment physical examinations. Of note, no adverse reactions such as abdominal pain, chest pain, shortness of breath, or other amphetamine-related effects were noted in these cases.
Despite these reports, the FDA still had problems regulating this supplement. In our case, the abdominal pain caused by the supplement allowed the FDA to move more quickly in stopping the importation of the product. On a recent Web search, the original Web site from which our patient obtained the supplement remained online and continued offering shipment of the product directly to consumers within the United States. Other Web sites that advertised the product fully acknowledged the news reports but still offered shipping within the United States. Bottles similar to the confiscated shipments are sold on www.herbathin.com (accessed on September 1, 2006), with the promise of similar “powers of the older version.” The Web site www.braziliandiet.com (accessed on September 1, 2006) contends that previous shipments were “contaminated” but continues to market the characteristic “Brazilian diet yellow” and “Brazilian diet orange” pills, although in a different container. Fortunately, the numerous reports from across the United States have halted further shipments of the product into this country.
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