Dietary Supplements Containing Ephedra: Health Risks and FDA's Oversight
Published: 2003-07-23T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: Dietary supplements containing ephedra have been associated with serious health-related adverse events, including heart attacks, strokes, seizures, and deaths. The Food and Drug Administration (FDA) regulates dietary supplements under the Dietary Supplement Health and Education Act of 1994 (DSHEA). Reports of adverse events have been received by FDA and others, including Metabolife International, the manufacturer of a dietary supplement containing ephedra, Metabolife 356. Because of concerns surrounding the safety of dietary supplements containing ephedra, GAO was asked to discuss and update some of the findings from its prior work on ephedra, including its examination of Metabolife International's records of health-related calls from consumers of Metabolife 356. Specifically, GAO examined (1) FDA's analysis of the adverse event reports it received for dietary supplements containing ephedra, (2) how the adverse events reported in the health-related call records collected by Metabolife International illustrate the health risks of dietary supplements containing ephedra, and (3) FDA's actions in the oversight of dietary supplements containing ephedra.
section_title: What GAO Found
paragraphs: FDA has used the adverse event reports it has received to conclude that dietary supplements containing ephedra pose a significant public health hazard. Since February 1993, FDA has received 2,277 reports of adverse events associated with dietary supplements containing ephedra, 15 times more reports than it has received for the next most commonly reported herbal dietary supplement. The types of adverse events that GAO identified in the health-related call records from Metabolife International were consistent with the types of adverse events reported to FDA and with the documented physiological effects of ephedra. Although call records contained limited information for most of the reports, GAO identified 14,684 call records that had reports of at least one adverse event among consumers of Metabolife 356. GAO's count of 92 serious events--heart attacks, strokes, seizures, and deaths--was similar to that of other reviews of the call records, including counts by Metabolife International and its consultants. Many of the serious events were reported among relatively young consumers--more than one-third concerned consumers who reported an age under 30. In addition, for call records containing information on the amount of product consumed or length of product use, GAO found that most of the reported serious adverse events occurred among consumers who followed the usage guidelines on the Metabolife 356 label. As part of its oversight of dietary supplements, FDA has taken some actions specifically focused on dietary supplements containing ephedra. FDA has issued warnings that focus on improper labeling, issued warnings to consumers, and issued a proposed rule in 1997 that, among other things, would require a health warning on the label of dietary supplements containing ephedra and prohibit a dietary supplement from containing both ephedra and a stimulant. FDA subsequently banned the sale of certain classes of over-the-counter drugs containing ephedrine and related alkaloids--the active ingredient in ephedra--in combination with an analgesic or stimulant. As the 1997 proposed rule has not been finalized, there is no rule prohibiting the marketing of dietary supplements with similar ingredients, and many dietary supplements with ephedra, such as Metabolife 356, also include caffeine or other stimulants. To receive comments on new evidence, FDA recently reopened the comment period for the proposed rule, and FDA reported to GAO that the agency is in the process of reviewing comments it has received and has not reached a decision regarding further action.

section_title: Letter
paragraphs: I am pleased to be here today as the Subcommittee considers concerns  about the safety of dietary supplements containing ephedra. More than  half of U.S. adults are overweight or obese, and more than one-third are  trying to lose weight. Many Americans have turned to dietary supplements  to help them lose weight. The most widely used weight loss supplement  ingredient is ephedra, which is also referred to as ma huang. The dietary  supplement industry has estimated that as many as 3 billion servings of  dietary supplements containing ephedra are consumed each year in the  United States. Medical experts have expressed concerns about the safety  of dietary supplements containing ephedra. Reports of adverse health  events associated with such supplements, including reports of heart  attack, stroke, seizure, and death, have been received by the Food and  Drug Administration (FDA) and others, including Metabolife International,  the manufacturer of a dietary supplement containing ephedra, Metabolife  356.
The Dietary Supplement Health and Education Act of 1994 (DSHEA)  created a framework for FDA’s regulation of dietary supplements as part  of its oversight of food safety. Since dietary supplements are generally  marketed without prior FDA review of their safety, FDA relies on  voluntary reports of adverse events from consumers, health professionals,  manufacturers, and others in its effort to oversee the safety of marketed  dietary supplements.
Because of concerns surrounding the safety of dietary supplements  containing ephedra, you asked us to discuss some of the findings from our  prior work on ephedra. My remarks today will focus on (1) FDA’s analysis  of adverse event reports it has received about dietary supplements  containing ephedra, (2) how the adverse events reported in the call  records received by Metabolife International illustrate the health risks of  dietary supplements containing ephedra, and (3) FDA’s actions in the  oversight of dietary supplements containing ephedra.
This testimony is based primarily on our earlier reports on dietary  supplements, including our March 2003 review of health-related call  records received by Metabolife International. For this testimony, we also  conducted additional analyses of the data in the Metabolife International  call records, obtained updated information from FDA about its oversight  efforts and adverse event reports that it has received concerning ephedra,  and reviewed FDA analyses of the safety of dietary supplements  containing ephedra. We conducted our work from June 2003 through July  2003 in accordance with generally accepted government auditing  standards.
In summary, FDA has determined that dietary supplements containing  ephedra pose a significant public health hazard based on the 2,277 adverse  events reports it has received. The number of adverse event reports FDA  has received for dietary supplements containing ephedra is 15 times  greater than the number it has received for the next most commonly  reported herbal dietary supplement. While it is difficult to establish with  certainty that a particular adverse event has been caused by the use of  ephedra, based on the pattern of adverse event reports it has received and  the scientific literature it has reviewed, FDA has concluded that ephedra  poses a risk of cardiovascular and nervous system effects among  consumers who are young to middle-aged.
The types of adverse events that we identified in the health-related call  records from Metabolife International were consistent with the types of  adverse events reported to FDA and with the documented physiological  effects of ephedra. Although the call records contained limited  information for most of the reports, we identified 14,684 call records that  contained reports of at least one adverse event among consumers of  Metabolife 356. Our count of 92 serious events—heart attacks, strokes,  seizures, and deaths—was similar to that of other reviews of the call  records, including counts by Metabolife International and its consultants.  Many of the serious events were reported among relatively young  consumers—more than one-third concerned consumers who reported an  age under 30. In addition, for the call records containing information on  the amount of product consumed or length of product use, we found that  most of the reported serious adverse events occurred among consumers  who followed the usage guidelines on the Metabolife 356 label—the  consumers reported that they did not take more of the product or take it  for a longer period than the company recommended.
As part of its oversight of dietary supplements, FDA has taken some  actions specifically focused on dietary supplements containing ephedra.  FDA has issued warnings to manufacturers that focus on improper   product labeling, issued warnings to consumers, and issued a proposed  rule in 1997 that, among other things, would require a health warning on  the label of dietary supplements containing ephedra and prohibit a dietary  supplement from containing both ephedrine alkaloids—the active  ingredient in ephedra—and a stimulant. FDA subsequently banned the sale  of certain classes of over-the-counter drugs containing ephedrine and  related alkaloids in combination with an analgesic or stimulant. As the  1997 proposed rule has not been finalized, there is no rule prohibiting the  marketing of dietary supplements with similar ingredients, and many  dietary supplements with ephedra, such as Metabolife 356, also include  caffeine or other stimulants. To receive comments on new evidence, FDA  recently reopened the comment period for the proposed rule, and FDA  reported to us that the agency is in the process of reviewing comments it  has received and has not reached a decision regarding further action.
subsections: section_title: Background
paragraphs: Ephedra, the most widely used ingredient in dietary supplements for  weight loss, is a powerful stimulant that can affect the nervous and  cardiovascular systems. Adverse events among consumers of dietary  supplements containing ephedra have been described in scientific  literature and in detailed adverse event reports. Because of concerns  about the risks of ephedra, medical organizations, states, and athletic  associations have sought to reduce the use of dietary supplements  containing ephedra.
subsections: section_title: FDA Oversight of Dietary Supplements under DSHEA
paragraphs: Under DSHEA, FDA regulates dietary supplements, including vitamins,  minerals, herbs and other botanicals, amino acids, certain other dietary  substances, and derivatives of these items. DSHEA requires that dietary  supplement labels include a complete list of ingredients and the amount of  each ingredient in the product. Dietary supplements may not contain  synthetic active ingredients that are sold in over-the-counter drugs and  prescription medications and cannot be promoted as a treatment,  prevention, or cure for a specific disease or condition.
Under DSHEA, manufacturers are responsible for ensuring the safety of  dietary supplements they sell. Dietary supplements do not need approval  from FDA before they are marketed; thus FDA generally addresses safety  concerns only after dietary supplements are marketed. DSHEA does not  require manufacturers to register with FDA, identify the products they  manufacture, or provide reports of adverse events to FDA. Mechanisms  that FDA uses to oversee dietary supplements and other products it  regulates differ (see app. I for more details).
Since manufacturers of dietary supplements are not required to provide  reports of adverse events to FDA, the agency relies on voluntary  postmarket reporting of adverse events to better understand the safety of  dietary supplements. Some individual adverse event reports are especially  valuable to FDA because they include enough information to help FDA  determine if the adverse event was likely caused by the supplement. These  reports include information about the receipt of medical care, health care  professionals’ attribution of adverse events to the consumption of dietary  supplements, the consumer’s appropriate use of the products, the  consumer’s use of other products, underlying health conditions and other  alternative explanations for the adverse event, and the consistency of  symptoms with the documented effects of the dietary supplement.
FDA, through the Department of Justice, can take enforcement action in  court against dietary supplements that are adulterated to remove them  from the market. A dietary supplement is considered adulterated under a  number of circumstances, including when it    presents a “significant or unreasonable risk of illness or injury” under the  conditions of use recommended or suggested in its labeling, or under  ordinary conditions of use if there are no suggestions or recommendations  in the labeling, or    bears or contains any “poisonous or deleterious substance” which may  render it injurious to health under the conditions of use recommended or  suggested in its labeling.
Instead of going to court, FDA may choose to take administrative action to  prohibit the sale of dietary supplements it considers to be adulterated.  FDA can promulgate a regulation declaring a particular dietary  supplement to be adulterated. FDA has not taken this action with any  dietary supplement. FDA can also issue an advisory letter explaining why  it considers the dietary supplement to be adulterated. The advisory letter  provides guidance to the industry regarding FDA’s opinion and notifies the  public that FDA may take legal action against firms or individuals that do  not follow the letter’s advice. FDA has done this for two dietary  supplement ingredients, comfrey and aristolochic acid.
In addition, although it has never been done, the Secretary of Health and  Human Services (HHS) may declare that a dietary supplement is  adulterated because it poses an “imminent hazard” to public health or  safety. In doing so, the Secretary must initiate an administrative hearing to  affirm or withdraw the declaration.
section_title: Health Concerns about Ephedra
paragraphs: Ephedra has been associated with numerous adverse health effects. As we  previously reported, case reports and scientific literature have suggested  that ephedrine alkaloids can increase blood pressure in those with normal  blood pressure, predispose certain individuals to rapid heart rate, and  cause stroke, among other things. We also reported descriptions of  adverse events associated with ephedrine alkaloids that affected the  central nervous system, such as seizures, mania, and paranoid psychoses.
FDA has received reports of adverse events associated with dietary  supplements containing ephedra, including heart attack, stroke, seizure,  psychosis, and death, that are consistent with the scientific literature. In  February 2003, the RAND Corporation released a review of the scientific  evidence on the safety and efficacy of dietary supplements containing  ephedra and concluded that a sufficient number of cases of these same  types of events had occurred in young adults to warrant further scientific  study of the causal relationship between ephedra and these serious  adverse events. RAND also found that use of ephedra or ephedrine plus  caffeine is associated with a number of other adverse effects, including an  increased risk of nausea, vomiting, heart palpitations, and psychiatric  symptoms such as anxiety and change in mood.
Because of these health concerns, many organizations and jurisdictions  have taken actions aimed at reducing the use of dietary supplements  containing ephedra. The American Medical Association and the American  Heart Association have urged FDA to ban the sale of dietary supplements  containing ephedra. In January 2002, Health Canada issued a Health  Advisory for Canadians not to use certain products containing ephedra,  especially those that also contain caffeine and other stimulants. In 2003,  Illinois banned the sale of products containing ephedra and other states  have similar bans under consideration. In addition, some states have  banned the sale of such products to minors or required label warnings.  Several sports organizations, including the NCAA, the National Football  League, the U.S. Olympic Committee, and the International Olympic  Committee, have banned the use of ephedra by their athletes.
In 2003, General Nutrition Centers, the nation’s largest specialty retailer of  nutritional supplements, discontinued the sale of products containing  ephedra, as have three other major retail outlets. Some manufacturers  have stopped producing dietary supplements containing ephedra. Other  manufacturers continue to offer dietary supplements containing ephedra  while also offering similar products that are ephedra-free.
section_title: Adverse Event Reports Have Led FDA to Conclude That Dietary Supplements Containing Ephedra Pose a Significant Public Health Hazard
paragraphs: Using the adverse event reports it has received and evidence from the  scientific literature, FDA has concluded that dietary supplements  containing ephedra pose a “significant public health hazard.” FDA and  others have received thousands of reports of adverse events among users  of dietary supplements containing ephedra, more than for any other  dietary supplement ingredient. Metabolife International also received  thousands of reports of adverse events.
subsections: section_title: More Adverse Events Have Been Reported for Products Containing Ephedra Than for Any Other Dietary Supplement
paragraphs: FDA has received more reports of adverse events for dietary supplements  containing ephedra than for any other dietary supplement ingredient. In  addition, poison control centers and one manufacturer, Metabolife  International, have received thousands of reports of adverse events  associated with dietary supplements containing ephedra. From February  22, 1993, through July 14, 2003, FDA received 2,277 reports of adverse  events associated with dietary supplements containing ephedra, which  was 15 times more reports than it received for the next most commonly  reported herbal dietary supplement, St. John’s wort.
Other organizations also have received a large number of adverse event  reports for dietary supplements containing ephedra. The American  Association of Poison Control Centers received 1,428 reports of adverse  events associated with dietary supplements containing ephedra, either  alone or in combination with other botanical dietary supplement  ingredients, in 2002, nearly two-thirds as many as FDA received over a 10- year period. The centers noted that there were more reports of adverse  events for ephedra-containing dietary supplements than for others.  Further, as we reported in March 2003, Metabolife International had 14,684  health-related call records that contained reports of adverse events  associated with its product, Metabolife 356, from May 1997 through July  2002. Neither the American Association of Poison Control Centers nor  Metabolife International is required to report these adverse events to FDA.
section_title: FDA Has Determined That the Adverse Event Reports and Scientific Literature Indicate That Dietary Supplements Containing Ephedra Pose a Significant Public Health Hazard
paragraphs: From the adverse event reports it has received and the scientific literature  it has reviewed, FDA concluded in March 2000 that dietary supplements  containing ephedra pose a significant public health hazard that primarily  involves consumers who are young to middle-aged and can result in  adverse cardiovascular and nervous system effects. It further concluded  that many of the adverse events were serious, resulting in morbidity and  mortality that would not be expected in a young population and that could  further compromise the health of more vulnerable older adults or those  with underlying conditions.
A study commissioned by FDA estimated that the agency receives reports  for less than 1 percent of adverse events associated with dietary  supplements. Although causality cannot be determined based on the  individual adverse event reports FDA receives, the agency uses these  reports to identify possible risks to consumers from dietary supplements.  As we have previously reported, there are well-known weaknesses in the  current system of voluntary reporting of adverse events, such as different  interpretations in determining an adverse event, underreporting,  difficulties estimating population exposure, and poor report quality.  Despite these limitations, FDA maintains that even isolated reports can be  definitive in associating products with an adverse effect if the report  contains sufficient evidence, such as supporting medical documents, a  temporal relationship between the product and effect, and evidence of  dechallenge and rechallenge.
section_title: Metabolife International Call Records Contain Reports of Adverse Events That Are Consistent with the Types of Adverse Events Reported to FDA
paragraphs: The types of adverse events that we identified in the Metabolife  International call records are consistent with the types of adverse events  reported to FDA and with the documented physiological effects of  ephedra. As we recently reported, most of the Metabolife International call  records contained limited information about the event and the consumer.  Nonetheless, the call records contribute to existing knowledge about  adverse events that have been associated with ephedra use. In our review,  we identified 14,684 call records that contained reports of at least one  adverse event among consumers of Metabolife 356. Within these call  records, we found 92 reports of serious adverse events—heart attacks,  strokes, seizures, and deaths—a count that was similar to that of other  reviews of the call records. In addition, the call records contain reports of  serious adverse events in consumers who were young and among those  who used the product within the recommended guidelines. These findings  are consistent with reports FDA has received regarding dietary  supplements containing ephedra.
subsections: section_title: Consumer Information in the Metabolife International Call Records Was Limited
paragraphs: In our review of health-related call records for users of Metabolife 356,  we found that the information in the call records was limited. Call records  were sometimes difficult to read and interpret, and consumer information  was not consistently recorded. In some cases, the evidence for a report of  an adverse event was limited to a single word on a call record. In other  cases, information was entered into a form developed by Metabolife  International with multiple boxes for consumer- and event-related  information. Most call records did not document complete information  about the consumer’s age, sex, weight, and height. Because the company  did not systematically follow up on calls reporting adverse events, and the  adverse events were not reported to FDA, it is not possible to gather more  complete information or medical records.
section_title: Metabolife International Call Records Contained Reports of Thousands of Adverse Events, Some of Which Were Serious, among Consumers of Metabolife 356
paragraphs: As we reported in March 2003, we identified 14,684 call records that  contained at least one report of an adverse event among consumers of  Metabolife 356. The types of reported adverse events were consistent  with the cardiovascular and central nervous system effects that have been  associated with ephedra products in the literature, adverse event reports  received by FDA, other case reports, and RAND’s review. Within the call  records, we identified 92 reports of heart attack, stroke, seizure, and death  (see table 1). Our count of reports of these serious adverse events was  similar to that of other reviews of the Metabolife International call records,  including counts by Metabolife International and its consultants.
We also found 1,079 reports of other types of adverse events that FDA  identified as serious or potentially serious. These included chest pain,  significant elevations in blood pressure, systemic rash, and urinary  infection. In addition to these 1,079 reports, we found records that  contained reports of a broad range of other types of adverse events,  including changes in heart rate such as palpitations and increased heart  rate; blood in stool; blood in urine; bruising; hair loss; and menstrual  irregularity.
subsections: section_title: Reports of Serious Adverse Events Involved Consumers Who Were Relatively Young
paragraphs: Within the subset of call records that contained information on age, the  distribution of ages suggests that a relatively young population was  experiencing the reported serious adverse events. Among the call records  that contained a report of a serious event, 44 percent included information  on age. For these call records, more than one-third concerned consumers  who reported an age under 30—the average reported age was 38 (ranging  from 17 to 65). As noted above, FDA has also received reports of serious  adverse events occurring in a population of young adults. Because we do  not know the age profile of all Metabolife 356 consumers, we cannot  determine if the age distribution among those reporting serious adverse  events in the Metabolife International call records reflects that age profile.
section_title: Serious Adverse Events Were Reported among Consumers Who Used Metabolife 356 within Recommended Guidelines
paragraphs: Within the subset of Metabolife International call records that contained  information on how the product was used by the consumer, most of the  reported serious adverse events occurred among consumers who reported  using the product within the guidelines on the Metabolife 356 label—that  is, who reported that they did not take more of the product or take it for a  longer period than recommended. Information about product use,  however, was incomplete—40 and 55 percent of the call records that  reported a serious event contained information about the amount of  Metabolife 356 used and the duration of use, respectively. Among the call  records that reported a serious adverse event and also contained  information about product use, 97 percent of consumers reported using an  amount of product within the recommended guidelines. Similarly, 71  percent of those consumers reported using the product for a length of time  that was within the recommended guidelines. This pattern is consistent  with findings from FDA’s review of adverse events associated with  ephedra products.
section_title: FDA Has Taken Some Actions to Oversee Dietary Supplements Containing Ephedra
paragraphs: As part of its oversight of dietary supplements, FDA has taken some  actions specifically focused on dietary supplements containing ephedra.  FDA has issued warnings that focus on improper product labeling, issued  warnings to consumers, and issued a proposed rule in 1997 that, among  other things, would require a health warning on the label of dietary  supplements containing ephedra and prohibit a dietary supplement from  containing both ephedra and a stimulant. However, parts of this rule  remain under consideration 6 years after it was first proposed.
As we previously reported, FDA has focused its enforcement actions  regarding dietary supplements on improper labeling. For example, in  February 2003, FDA issued warning letters to 26 firms that sell dietary  supplements containing ephedra. All of these letters advised marketers  that label claims for enhancement of physical performance were  unsubstantiated and the products were therefore misbranded.
FDA and HHS have also directly warned consumers about the safety of  dietary supplements containing ephedra. In February 1995, FDA issued a  press release warning consumers about a specific dietary supplement  product that contained both ephedra and caffeine, because it had  determined that the product represented a threat to public health. Further,  in February 2003, the Secretary of HHS issued a statement to caution  people against using dietary supplements containing ephedra and  indicated that FDA continues to have serious concerns about the risks of  these dietary supplements.
FDA has also taken actions in its oversight of dietary supplements in  general. Specifically, FDA has conducted facility inspections and  proposed good manufacturing practice (GMP) regulations that focus on  product quality in general, not the safety of an individual ingredient.
FDA first issued a proposed rule to regulate dietary supplements  containing ephedrine alkaloids in 1997. The proposed rule would    define the amount of ephedrine alkaloids in a serving of dietary  supplement at and above which the product would be deemed adulterated  (8 milligrams),    establish labeling requirements regarding maximum frequency of use and  daily serving limits,  require that labels on these supplements contain a statement warning that  the product should not be used for more than 7 days,    prohibit the use of ephedrine alkaloids with ingredients that have a known  stimulant effect (e.g., caffeine),    prohibit labeling claims that promote long-term intake of the supplements  to achieve the purported purpose,  require a warning statement in conjunction with claims that encourage  short-term excessive intake to enhance the purported effect, and  require that specific warning statements appear on product labels.
Our 1999 report on the proposed rule was critical of the science FDA used  to support the serving size and duration of use limits in the proposed  rule. However, we did not conclude that dietary supplements containing  ephedra were safe, and we commented that the adverse events reported to  FDA were serious enough to warrant FDA’s further investigation of  ephedra safety. Primarily, we were concerned that FDA used only 13  adverse event reports to establish serving limits and had weak support for  proposed limits on duration of use. Partly as a result of our review, FDA  withdrew the sections of the proposed rule on serving size and duration of  use limits.
In the interim, FDA has taken action to regulate certain drugs that contain  ephedrine, the active ingredient in ephedra. In September 2001, FDA  issued a final rule stating that certain over-the-counter drugs containing  ephedrine and related alkaloids in combination with an analgesic or  stimulant could not be marketed as over-the-counter drugs. There  currently is no similar rule prohibiting the marketing of dietary  supplements containing ephedra in combination with analgesics or  stimulants, such as caffeine. As a result, dietary supplements may contain  ingredients that are prohibited in drugs. In fact, many dietary supplements  with ephedra, such as Metabolife 356, also include caffeine. The proposed  rule contains a provision that would prohibit dietary supplements from  containing both ephedra and other stimulants.
In March 2003, almost 6 years after the initial proposal, FDA reopened the  comment period for the remaining provisions of this proposed rule for 30  days. FDA sought comments on three areas:    New evidence on health risks associated with ephedra.
Whether the currently available evidence and medical literature  demonstrate that dietary supplements containing ephedra pose a  “significant or unreasonable risk of illness or injury” under the conditions  of use recommended or suggested in their labeling, or under ordinary  conditions of use if there are no suggestions in the labeling.
A new warning label for ephedra products that warns about reports of  serious adverse events after the use of ephedra, including heart attack,  seizure, stroke, and death; cautions that the risk can increase with the  dose, with strenuous exercise, and with other stimulants such as caffeine;  specifies certain groups (such as women who are pregnant or breast  feeding and persons under 18) who should not use these products; and  lists other diseases, such as heart disease and high blood pressure, that  should rule out the use of ephedrine alkaloids.
On July 14, 2003, FDA reported to us that the agency is in the process of  reviewing the comments and has not reached a decision regarding further  action. While FDA has not attempted to ban the marketing of dietary  supplements containing ephedra, the agency has sought, in these  comments, additional information that would help it determine whether or  not such action would be warranted.
section_title: Concluding Observations
paragraphs: Because the regulatory framework for dietary supplements is primarily a  postmarketing program and FDA does not review the safety of dietary  supplements before they are marketed, adverse event reports are  important sources of information about the health risks of dietary  supplements containing ephedra. It is often difficult to demonstrate  conclusively that a single reported adverse event was caused by ephedra,  but some individual reports, particularly when they are complemented by  follow-up investigation of the case, can be especially informative.  Although the information in the Metabolife International call records we  examined was limited, the types of adverse events we observed were  consistent with the known risks of ephedra, including serious events such  as five reports of death. Based on the pattern of adverse event reports FDA  has received and the consistency of those reports with the known effects  of ephedra from the scientific literature, the agency concluded 3 years ago  that dietary supplements containing ephedra pose a “significant public  health hazard.” FDA is currently reviewing information that will help the  agency determine what further actions are warranted.
Mr. Chairman, this completes my prepared statement. I would be happy to  respond to any questions you or other Members of the Subcommittee may  have at this time.
section_title: Contact and Acknowledgments
paragraphs: For more information regarding this testimony, please call Marcia Crosse  at (202) 512-7119. Key contributors include Martin T. Gahart, Carolyn Feis  Korman, Chad Davenport, Roseanne Price, and Julian Klazkin.
section_title: Appendix I: Mechanisms for FDA Oversight of Different Types of Products
paragraphs: Mandatory  manufacturer  reporting of  adverse events  Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, Pub.L.  No. 107-188, 116 Stat. 594, manufacturers and distributors are required to registered with FDA no  later than December 13, 2003.
Monograph drugs are typically over-the-counter drugs that must adhere to specific safety standards  set for each ingredient and do not undergo clinical testing.
New Drug Applications must be submitted to FDA for all prescription drugs and some over-the- counter drugs prior to marketing. This application must include data that demonstrate the safety and  efficacy of the product.
This is a work of the U.S. government and is not subject to copyright protection in the  United States. It may be reproduced and distributed in its entirety without further  permission from GAO. However, because this work may contain copyrighted images or  other material, permission from the copyright holder may be necessary if you wish to  reproduce this material separately.