Opening Remarks

• The Honorable John McCain
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  Opening Remarks

  The Honorable John McCain

  I thank the witnesses for appearing before the Committee today, especially those who made special arrangements to be here. • The purpose of this hearing is to examine whether the current regulation of dietary supplements adequately informs and protects American consumers from the potential adverse health risks associated with the use of certain supplements. Dietary supplements, as the witnesses can attest, are readily available – from the malls to the Internet – to consumers of all ages, and often are promoted with questionable marketing practices. • I joined many of my colleagues in 1994 in supporting the Dietary Supplements Health and Education Act (DSHEA or the Act). The intent of the Act was to alleviate certain unnecessary pre-market approval regulations on vitamins, minerals, and herbs, which were considered safe supplements to the human diet. At that time, the objective was to strike a balance between providing consumers with better access to supplements that could be used to improve their health on the one hand, and maintaining minimum health and safety protections for such consumers on the other. • While it is true that DSHEA has succeeded in freeing many safe and useful supplements from unnecessary regulation, it is equally true that the Act appears to have provided a safe haven for substances that many experts believe pose potentially serious health risks. • Of particular concern to many is the heavy use of supplements among teenagers. A 2001 national survey of 785 teens by Blue Cross Blue Shield estimated that one million American kids between 12 to 17 years old – roughly four percent of that age group – take at least one performance-enhancing sports supplement. • Members of school sports teams appear particularly vulnerable to the lure of performance-enhancing dietary supplements. For example, a 2001 study of 1,102 high school athletes in Westchester County, New York, found that 44 percent of the seniors, nearly all boys, had tried creatine. This is not surprising given that supplement manufacturers appear to target adolescent users through the use of enticing teen-friendly product names that incorporate terms like “Extreme” and “Gen-X.” • While the long-term health consequences from the use of certain supplement are unknown, health experts warn that dietary supplements such as steroid precursors interfere with normal growth and bone development, cause hormonal imbalances, liver and kidney damage, and an increased risk of certain types of cancer. In fact, there is increasing concern in the medical community that today’s use of certain supplements could create a health crisis in the future. • The Committee will hear testimony today about whether American consumers are relying to their detriment on the notion that, simply because supplements are so easily available and not illegal, they must be safe. • I thank the witnesses again for being here and I look forward to your testimony. # # #

Testimony

• Mr. John M. Taylor
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  Testimony

  Mr. John M. Taylor

  Click here for a Microsoft Word version of Mr. Taylor's remarks.

Witness Panel 2

• Mr. Greg Davis
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  Witness Panel 2

  Mr. Greg Davis

  No testimony submitted.

• Mr. Charles Bell
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  Witness Panel 2

  Mr. Charles Bell

  Good morning, Chairman McCain, Ranking Member Hollings, and other members of the Committee. Thank you for providing me the opportunity to come before you today. I am Charles Bell, Programs Director for Consumers Union . Consumers Union is the nonprofit publisher of Consumer Reports magazine. Our mission at Consumers Union is to test products, inform the public, and protect consumers. Today I offer this testimony on dietary supplements as part of our consumer protection function. The 1994 Dietary Supplement Health and Education Act of 1994 (DSHEA) opened the floodgates to thousands of untested herbal products and handcuffed the Food and Drug Administration from performing any meaningful oversight over what has since developed into a multibillion-dollar industry. The law allows anyone to launch a product with a health claim without clearance from any government agency. There’s no assurance of either safety or efficacy. And what’s on the label is sometimes not in the pill. The contrast with regulatory standards for pharmaceutical drugs is striking. A proposed new drug can only be approved if it is deemed to be safe in multiple human studies, and companies are required to notify the FDA if consumers suffer serious side effects. While many dietary supplements are generally safe, and many have important health benefits for consumers, there is a significant and growing number of highly questionable products that would probably not be allowed on the market if they were subject to pre-market safety testing. In 1995, Consumer Reports magazine published a list of five supplements that according to the FDA can cause serious harm to consumers – chaparral, ephedra, comfrey, lobelia, and yohimbe. Eight years later, all five of these supplements are still being marketed and sold. In the aftermath of DSHEA, unsafe dietary supplement products can remain on the market for many years, in the same stream of commerce as products approved by the FDA as safe and effective for their intended use. Further, new dietary supplement products can be introduced overnight that contain novel, untested ingredients and/or novel combinations of new and/or existing supplement ingredients. Health providers and public health authorities typically receive little pre-market or post-market information about how such products may affect human health, and interact with medicines that patients are already taking. Even where serious problems are documented, such as in the case of supplements like ephedra, which is discussed in detail below, it is difficult for the FDA to take prompt action to protect consumers. EPHEDRA: A CASE STUDY OF AN UNCONTROLLED HAZARD TO PUBLIC HEALTH Over the last several years, increasing public attention has focused in particular on the sale and marketing of herbal supplements containing ephedra or ma huang. The ephedra controversy is an important case study, in part because it has been responsible for the largest number of reported adverse events. The U.S. Food and Drug Administration (FDA) has compelling data showing that ephedra poses serious and unreasonable health risks to consumers. Other studies, including our own analysis of the literature to date, reveal that risks from the use of ephedra far outweigh any benefits. For example, a comprehensive report appearing in the March 26, 2003 issue of The Journal of the American Medical Association, linked the use of ephedra with risks of heart, psychiatric, and gastrointestinal problems, while finding insufficient evidence to support its use to enhance athletic performance, or to promote long-term weight loss. We believe that an outright ban of this particularly hazardous herbal supplement for both children and adults is badly needed to protect consumers from serious potential adverse health effects, including heart attacks, seizures and strokes. THE FDA AND OTHER HEALTH AUTHORITIES HAVE RECEIVED MANY REPORTS OF THE HARMFUL EFFECTS OF EPHEDRA Dietary supplement products containing ephedra provide dubious health benefits while posing serious health risks to consumers. From January 1993 through October 2000, the FDA received 1,398 reports of adverse events linked to herbal supplements containing ephedra, including 81 deaths, 32 heart attacks, 62 reports of cardiac arrhythmia, 91 reports of hypertension, 69 strokes and 70 seizures. Complaints about herbal supplements containing ephedra constituted 42% of all dietary supplement complaints, and 59% of all reported deaths. Those complaints likely represent only the tip of the iceberg, because the vast majority of adverse reactions to dietary supplements or medications are never reported to the FDA, or indeed, to any health professional or agency. The American Association of Poison Control Centers has reported a steadily increasing number of serious adverse events related to supplements containing ephedra over the last five years. Recent data released by the AAPCC indicates that in the year 2001 alone there were: · 812 reported events relating to exposure to dietary supplements containing ephedra as a sole ingredient, including 3 deaths, 103 adverse reactions, 10 "major effects" (defined as exhibiting signs or symptoms that were life-threatening or resulted in significant residual disability) and 139 "moderate effects" (defined as exhibiting symptoms or signs that were more pronounced, more prolonged or more systemic in nature than minor symptoms -- and where usually some form of treatment is indicated). Of the 812 exposures, 440 persons (54%) were treated in a health care facility. 48% of reported exposures occurred in individuals over 19 years of age. · 7,115 reported events linked to exposures to multi-botanical supplements containing ephedra as an ingredient, including 3 deaths, 1,075 adverse reactions, 87 "major effects" and 1,325 "moderate effects." Of the 7,115 exposures, 3,849 persons (54%) were treated in a health care facility. 43% of reported exposures occurred in individuals over 19 years of age. In addition to the above, according to information released by Public Citizen Health Research Group, from 1997 through part of 2001, as many as 33 members of the U.S. military died in ephedra-related deaths. Those who died were between their early 20s and early 40s and were reportedly in good health. As a result, the Army and Air Force military exchanges have removed such products from military commissary shelves worldwide. THERE IS COMPELLING EVIDENCE THAT EPHEDRA POSES SERIOUS RISKS TO CONSUMERS Two recent independent studies from well-respected academic centers, reported in peer-reviewed journals, scrutinized adverse events reports filed with the FDA between 1995 and 1999. In the reports, researchers found dozens of cases of abnormal heartbeats, strokes and heart attacks that were likely related to ephedra use. Samenuk and others at the New England Medical Center in Boston analyzed almost 1,000 cases of possible ephedra toxicity submitted to the FDA. They reported in a recent issue of Mayo Clinic Proceedings that untoward events were clearly related to immediate prior use of the drug in 37 people, and that 36 of these 37 victims had taken the product according to the manufacturer’s directions. Sixteen suffered a stroke; 10 had a heart attack; and 11 died. The study concluded that "ma Huang use is temporally related to stroke, myocardial infarction, and sudden death; (2) underlying heart or vascular disease is not a prerequisite for ma Huang–related adverse events; and (3) the cardiovascular toxic effects associated with ma Huang were not limited to massive doses." In the December 21, 2000 issue of The New England Journal of Medicine, Haller and Benowitz from the University of California in San Francisco analyzed 140 cases of alleged ephedra toxicity that were reported to the FDA from 1997 to 1999. Abnormal heart rhythms, increases in blood pressure, stroke, sudden death, and heart attack led the list. Of those reactions, 62 percent were thought to be “definitely or probably” or “possibly” due to ephedra. Eight of the 10 deaths were attributed to ephedra, including that of a 15-year-old girl. The few clinical studies that have been done to date are short-term and have used small numbers of subjects. Adverse reactions included elevated blood pressure, palpitations, chest pain, and extreme irritability. Dropout rates were high in the ephedra—using volunteers. In the March 26, 2003 issue of the Journal of the American Medical Association, Shekelle and colleagues published an evidence-based review of the efficacy and safety of ephedra and ephedrine. (This review was carried out under the auspices of the RAND Institute at the request of the FDA.) According to a summary of Shekelle’s analysis of safety data from 50 clinical trials: Evidence from controlled trials was sufficient to conclude that the use of ephedrine and/or the use of ephedra-containing dietary supplements or ephedrine plus caffeine is associated with two to three times the risk of nausea, vomiting, psychiatric symptoms such as anxiety and change in mood, autonomic hyperactivity, and palpitations. An additional evaluation of adverse event reports by Shekelle et al revealed 5 deaths, 4 myocardial infarctions, 11 cerebrovascular accidents, 4 seizures and 8 psychiatric cases as “sentinel events” associated with prior consumption of ephedra or ephedrine. According to an editorial article that appeared in the same issue of The Journal of the American Medical Association (JAMA): The results of this analysis cast doubt on any claims that use of dietary supplements containing ephedra or ephedrine can help achieve long-term weight loss or weight maintenance or enhance athletic performance. The findings also strongly suggest increased risk of serious adverse effects associated with these products. Moreover, reviewing the accumulated reports of toxicity linked to these compounds, it is hard not to be impressed by the number of serious cardiovascular complications in young adults. ADVERSE REACTIONS WITH OTHER MEDICATIONS IS A MAJOR SAFETY CONCERN Dietary supplements containing ephedra may interact in hard to predict ways with other prescription and over-the-counter medications that consumers are taking. For this reason, Consumers Union recommends that all consumers should consult their physicians before taking dietary supplements. For example, combinations of ephedra products and over-the-counter cold remedies are a major issue, according to Dr. Richard Cytryn of the New Jersey Chapter of the American College of Cardiology: Perhaps someone who has a cold does not want to interrupt a personal weight loss plan or a vigorous exercise program. He or she uses the herbal supplement and buys a sympathomemetic medication to alleviate cold symptoms. These people are actually unaware that they are taking a double dose of the drug, thereby compounding their vulnerability to its side effects. This can have potentially deadly results… Used indiscriminately, or in combination with contraindicated OTC medications, certain other herbs and even with caffeine, ephedra supplements can lead to severe physiological responses. ADULT CONSUMERS ARE AT RISK, IN ADDITION TO CHILDREN While much of the discussion of the ephedra problem focuses on persons under 18, the hazards of ephedra are by no means limited to minors. Consumers Union’s chief medical adviser Dr. Marvin Lipman, a physician and emeritus professor of medicine at New York Medical College, is particularly concerned about the potential risks to adults who may have known or unknown conditions such as cardiovascular disease, diabetes and hypertension, or who may combine their intake of ephedra with caffeine, other herbal supplements and/or other medications. Further, adult consumers may turn to herbal supplements containing ephedra after many years of physical inactivity, without consulting physicians. As noted above, the AAPCC data indicates that roughly half of all adverse event reports received by poison control centers involve adult consumers. MANUFACTURERS HAVE SUPPRESSED INFORMATION REGARDING EPHEDRA-RELATED ADVERSE EVENTS Strong evidence has now emerged that manufacturers of dietary supplements containing ephedra have been concealing substantial numbers of consumer complaints regarding their products: On August 15, 2002, the Justice Department disclosed that it was investigating whether Metabolife (a major manufacturer and distributor of ephedra products), had made false statements to the FDA regarding the existence of consumer complaints about its products. On the same day, Metabolife announced that it would turn over 13,000 consumer health complaints or "adverse event reports" to the FDA. After analyzing the Metabolife adverse events reports, the special investigations division of the House Committee on Government Reform concluded that 2,000 of the 13,000 reports were "significant" effects, including three deaths, 20 heart attacks, 24 strokes, 40 seizures, 465 episodes of chest pains and 966 reports of heart rhythm disturbances. Two years ago, depositions in a lawsuit in San Francisco against E'ola (a Utah-based multilevel-marketing firm) regarding a death allegedly linked to ephedra revealed that the company had received 3,500 customer complaints about one of its ephedra weight-loss products. According to the San Francisco Chronicle, none of the complaints were ever disclosed to the FDA. While it isn't clear how many other manufacturers and sellers of ephedra products may be suppressing information regarding potential health effects, those examples do not inspire confidence that serious health impacts arising from the use of herbal supplements will be promptly reported to responsible health authorities under a voluntary reporting system. This also underscores the dangers of allowing herbal medicines in the marketplace without premarket safety testing and a rigorous post-marketing surveillance system. HEALTH ORGANIZATIONS, SPORTS ORGANIZATIONS, AND STATE GOVERNMENTS ARE CALLING FOR ACTION TO ADDRESS THE HAZARDS OF EPHEDRA Despite the large number of deaths and serious adverse events linked to ephedra use, and repeated requests from consumer and public health organizations, the FDA has failed to ban dietary supplements containing ephedra. We believe this is because the FDA has been hampered in its regulatory efforts by the restrictions placed on the Agency's regulatory authority under DSHEA. A broad range of health and sporting organizations have spoken out regarding ephedra’s hazards: · The American Medical Association has called for the FDA to remove products containing ephedra from the marketplace. · The American Heart Association issued a statement in early April stating that supplements containing ephedra “do more harm than good and should be removed from the market.” · The 2003 spring training death of 23 year-old Baltimore Orioles pitcher Steve Bechler prompted Major League Baseball to ban ephedra use by minor league baseball, and open talks with the MLB Players Association regarding these issues. · The National Football League, the National Collegiate Athletic Association and the International Olympic Committee have also banned Ephedra supplements. The deaths of three other prominent athletes, all football players -- Korey Stringer of the Minnesota Viking, Rashidi Wheeler of Northwestern University, and DeVaughn Williams of Florida State University -- have also been linked to herbal supplements containing ephedra. The NFL has joined with the Blue Cross Blue Shield Association and other sporting organizations to press for stronger federal regulation of anabolic steroids and ephedra products. · The American Council on Exercise, America’s Authority on Fitness and “workout watchdog” issued a statement in April 2003 urging Americans to avoid use of supplements containing ephedra and to consult their physicians before taking any dietary supplement. Concerned about the delay in federal action to ban ephedra, state and local governments are enacting legislation to address the ephedra problem directly. However, most government officials we have talked to have clearly stated that they do not have sufficient resources to address public health problems caused by ephedra, and that they would prefer for the FDA to address the hazards posed by ephedra and other supplements. · At least ten U.S. states, and several local governments have imposed various restrictions on ephedra sales, such as requiring a prescription, outlawing sales to minors, or limiting the maximum dose. · In 2002, California passed legislation prohibiting the sale of products containing ephedra to minors. The bill also required clear and conspicuous labels that warn consumers of specific potential health risks such as heart attack, stroke and death; indicate that sales to persons under 18 are prohibited; and provide the toll free number for FDA Medwatch to report adverse events. · In March 2003, Suffolk County, New York became the first county in the nation to ban the sale of herbal supplements containing ephedra to adults and kids. The Suffolk County bill was strongly supported by Karen and Tom Schlendorf of Northport, Long Island, whose son Peter died in 1998 after taking supplements containing ephedra while on spring break in Florida; and Doug Hanson, of Huntington, Long Island, whose wife passed away while working out in a gym after taking ephedra supplements in 1998. · In May 2003, the state of Illinois banned the sale of dietary supplements containing ephedra. Persons who sell supplements containing ephedra in Illinois can now be charged with a Class A misdemeanor, punishable by imprisonment for less than one year and/or a fine of not more than $5,000 for a first offense. · In July 2003, Westchester County, New York banned the sale of ephedra to adults, amending a recently passed law that prohibited sales to persons under 18. · In August 2003, New York state banned the sale of dietary supplements containing ephedra. · This month, California enacted legislation banning the sale, manufacture, and distribution of ephedra, which takes effect on January 1, 2004. EPHEDRA STIMULANTS ARE STILL WIDELY AVAILABLE Over the last two years, several major national retail chains, including CVS, GNC, Eckerd and 7-Eleven have announced that they will no longer stock dietary supplement products containing ephedra. Several major manufacturers, including TwinLab, Nature’s Bounty, and Cytodyne, have also announced that they will no longer make and distribute supplements containing ephedra. Consumer Reports and Consumer Reports on Health have published various articles regarding ephedra and other herbal supplements, and we continuing to investigate these issues. Our ongoing research suggests that: · Herbal supplements containing ephedra are still widely available at lower-profile retail sites such as independent pharmacies, gas stations and truck stops, and convenience and health food stores. · Ephedra is present not just in weight-loss supplements, the best known use, but also in supplements marketed as energy boosters or alternatives to street drugs such as ectasy and speed. · Ephedra akaloids are turning up in supplements under names that consumers may not recognize: epitonin, Ma Huang, sida cordifolia and sinica. · Labels listing ingredients are often in small print, and hard to decipher. Labels do not necessarily provide appropriate warning of potential hazards, or indicate how many milligrams of each substance are present. · Many ephedra supplements contain caffeine and/or other herbal compounds that contain caffeine, such as guarana, kola nut, paulina cupana, and mate, as well as green and black tea. Some products appear to far exceed the recommended daily intake for caffeine of 300 milligrams. · Consumers can’t necessarily rely on pharmacy or retail employees for accurate information about whether products contain ephedra or not. “EPHEDRA-FREE” PRODUCTS ARE NOT NECESSARILY SAFE It is important to realize that if and when ephedra is banned at the national level, we may see a variety of other dangerous, untested, unregulated herbal medicines drive right through the huge DSHEA loophole. There are certainly other herbal medicines that cause dangerous interactions that are also on the market today. While they have achieved less visibility, they are nevertheless of great concern to many medical professionals, researchers and patients. We have a serious concern that a variety of serious adverse events involving supplements that are less frequently taken will be overlooked, unless FDA and FTC are given adequate resources to investigate and take prompt enforcement actions. To take just one example, herbal supplement companies are rushing to market with a variety of compounds to create “ephedra-free” herbal supplements. But as Dr. Paul Coates of the National Institutes of Health’s Office of Dietary Supplements has warned, “The fact that a dietary supplement is ephedra-free is not a indication of its safety.” DSHEA LOOPHOLES PERMIT SALE AND MARKETING OF UNTESTED STEROID EQUIVALENTS Dangerous loopholes in DSHEA and the Controlled Substances Act that permit manufacturers to aggressively market and sell untested, unregulated steroid equivalents to the public, including persons under 18. A national survey conducted for the Blue Cross Blue Shield Association in 1999 found that 6 percent of youths ages 15 to 16 and 8 percent of 17- and 18-year-olds had taken a sports supplement. Yet as we noted in Consumer Reports magazine in June 2001, sports-medicine researchers have only tested products like androstenedione and creatine in adults. There has been no systematic testing of these drugs in minors, and for ethical reasons, such tests probably will not be conducted. Because of serious safety concerns, numerous sporting and medical organizations, including the AMA and the American Academy of Pediatrics, believe that steroid precursors should be classified as Controlled Substances. POST-MARKETING SURVEILLANCE OF DIETARY SUPPLEMENTS IS “AN INADEQUATE SAFETY VALVE” In April 2001, the Office of Inspector General at the Department of Health and Human Services concluded that FDA’s adverse event reporting system was “an inadequate safety valve” because of inadequate authority and organizational capacity to collect and take action on adverse event reports. The report noted that in contrast to requirements for monograph drugs and new drug application (NDA) drugs, manufacturers of dietary supplements are not required to register their companies or their products with the FDA. As a result, the FDA does not have a list of supplement products and ingredients when it receives an adverse event report. The Inspector General found that FDA was unable to determine the ingredients for 32 percent of products mentioned in adverse event reports (AERs). It also lacked product labels for 77 percent of the products mentioned in the AERs, and product samples for 69 percent of products that it requested. For products referenced in the AERs, FDA was unable to determine the manufacturer for 32 percent of the products, and the city and state for 71 percent of manufacturers. RECOMMENDATIONS 1) The FDA should ban the sale of ephedra and untested steroid equivalents for both minors and adults. If the FDA believes additional legal authority is needed to act on these matters, we strongly urge the Congress to provide that authority. At a minimum, we would support the provisions in the "Dietary Supplement Safety Act of 2003" (S. 722) that would require stimulants to be approved as new drugs, would declare foods containing unapproved stimulants to be adulterated, and prohibits the introduction into interstate commerce of a supplement containing a stimulant unless it is approved by the Secretary. These provisions would also be extremely helpful for addressing the hazards posed by herbal heart stimulants such as ephedra and steroid precursors. 2) Pre-market safety testing should be required for dietary supplements, particularly for stimulants deemed to be of special concern by FDA and other health authorities. Many consumers are surprised to learn the government does not currently evaluate the safety of dietary supplements before they are sold. This situation poses a serious risk to public health, and amounts to a vast, uncontrolled clinical trial on an unsuspecting public. Even Joseph Levitt, Esq., Director of the FDA’s Center for Food Safety and Applied Nutrition, testified in Congress in March 2001 that the current “regulation of dietary supplements is, for the most part, a post-marketing program.” We support the provisions in S. 722 that would authorize the Secretary of the Department of Health and Human Services (DHHS) to require the manufacturers of dietary supplements, or any ingredient in a dietary supplement to submit data demonstrating that the dietary supplement is safe. The Secretary would then be authorized to review the data and issue a determination that either the ingredient is safe and that continued marketing is approved, or that continued marketing is disapproved because either it is unsafe, or it has not been shown to be safe. 3) Dietary supplement manufacturers should be required to report adverse events to the FDA. The current voluntary reporting system provides insufficient information for public health authorities to take prompt action regarding harmful products that put consumers at serious risk. We strongly support provisions in S. 722 that would require manufacturers, packers and distributors of dietary supplement products to collect, review, and report serious adverse events suffered by consumers using their products to the Secretary of the Department of Health and Human Services (DHHS), within 15 days of receiving notice of the event. In addition, the bill would require dietary supplement manufacturers to report on all adverse events to DHHS annually. 4) Post-marketing surveillance for dietary supplements should be improved. We believe that the FDA must be given additional resources and a resounding mandate from the Congress to strengthen post-marketing surveillance of dietary supplements. As a first step, we support the provisions if S. 722 that would authorize the Secretary of DHHS to require manufacturers of dietary supplements to conduct postmarket surveillance if the Secretary determines that consumer use of a manufactured dietary supplement may result in serious adverse events. Once again, I thank Chairman McCain, and Ranking Member Hollings and the Committee for the opportunity to testify, and I look forward your questions.

• Mr. David Seckman
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  Witness Panel 2

  Mr. David Seckman

  Chairman McCain and Honorable Members of the Committee on Commerce, Science and Transportation, thank you for the opportunity to address the Committee with respect to the dietary supplement industry. I am David Seckman, executive director and CEO of the National Nutritional Foods Association (NNFA). NNFA was founded in 1936 and is the oldest and largest trade association in the natural products industry. We represent the interests of more than 5,000 retailers, manufacturers, suppliers and distributors of health foods, dietary supplements and related items. The Committee has asked that I address a number of issues regarding dietary supplements, including how these products are sold and the effectiveness of the law that governs them. Let me start with the law, as it underlies all that we will discuss here today. The Dietary Supplement Health and Education Act was unanimously passed in 1994 to balance the American consumer’s growing interest in health maintenance with the preservation of public safety. This legislation improved consumer access to dietary supplements and information about these products. It also increased consumer protection against unsafe products and false and misleading claims. In addition, it required supplement manufacturers to submit evidence of the safety of their products and the scientific basis for claims. DSHEA is often mischaracterized as lessening the Food and Drug Administration’s ability to regulate supplements. In fact, the enactment of DSHEA provided the FDA, the primary agency that regulates supplements, with increased enforcement powers by establishing new labeling and potency standards. Briefly, under DSHEA, the FDA has the power to: · Seize dietary supplements that pose an "unreasonable or significant risk of illness or injury" [Section 402 (f)]. · Stop the sale of an entire class of dietary supplements if they pose an imminent public health hazard [Section 402 (f)]. · Require dietary supplements to meet strict manufacturing guidelines (Good Manufacturing Practices), including potency, cleanliness, and stability [Section 402 (g)]. · Stop a new dietary ingredient from being marketed if the FDA does not receive enough safety data in advance [Section 413]. · Refer for criminal action any company that sells a dietary supplement that is toxic or unsanitary [Section 402 (a)]. · Obtain an injunction against the sale of a dietary supplement that has false or unsubstantiated claims [Section 403 (a), (r6)]. In evaluating the effectiveness of any law, there are two critical steps that must follow its enactment: implementation and enforcement. Laws only work if their provisions are put into practice and the failure to abide by them is monitored and punished. In regard to DSHEA specifically, and for a number of reasons, this law has never been fully implemented or adequately enforced. Before I discuss lack of implementation and enforcement of DSHEA, let me say that the FDA, under the leadership of Commissioner McClellan, has made progress in implementation of the law and has become more active in its enforcement. But there is still much more to be done. Let me give you a few examples. Good Manufacturing Practices A regulation for good manufacturing practices for dietary supplements, which was provided for by DSHEA, was only introduced this year, more than nine years after the law was enacted. Under the rule, manufacturers would be required to evaluate the identity, purity, quality, strength, and composition of their dietary ingredients and dietary supplements. The industry was not an impediment to the introduction of this regulation. In fact, the leading trade associations and their members encouraged and welcomed its release. In a substantive demonstration of industry support for a good manufacturing practices framework for dietary supplements, my organization created its own certification program five years ago. Now that FDA has proposed a regulation, we encourage its swift finalization, implementation and enforcement. Performance Enhancing Products There has been much concern voiced recently about the use of performance enhancing products in sports, particularly by high school athletes. Specifically targeted have been pro-hormone products such as androstenedione, or “andro.” Although the FDA has been asked for several years by both industry and lawmakers to determine whether these products are actually dietary supplements as defined by DSHEA, the agency has not responded. While I believe that the FDA has the authority under DSHEA to effectively deal with this issue, the controversy continues. With that in mind, the industry last week voiced its support for a new bill, S. 1780, the “Anabolic Steroid Control Act of 2003,” that will place andro and products like it under the Controlled Substances Act. Although this legislation, if enacted, will put to rest the argument about whether or not andro is a dietary supplement, it is unfortunate that we needed to resort to a complex and protracted legislative solution when a regulatory one would have been much swifter and more appropriate. Ephedra More than any other, ephedra is the product that has been pointed to as evidence of DSHEA’s lack of effectiveness. But what ephedra is really emblematic of is not DSHEA’s shortcomings, but the tentativeness and reluctance of the FDA in enforcing the law. No matter your opinion on the safety or effectiveness of ephedra, what should be indisputable is that DSHEA clearly provides the FDA with the power to take unsafe products off the market. And whether that action is validation of ephedra as a safe and useful dietary supplement or its removal from the marketplace, we fully support the FDA’s empowerment to act. Truth in Advertising The FDA is not alone in regulating dietary supplements. The Federal Trade Commission also has regulatory authority over what supplement manufacturers can say about their products in advertising or on the Internet. For example, in recent years the FTC has invested substantial time and resources in cracking down on online supplement advertisers who disobey the law. While the industry applauds and supports these efforts, I would like to point out that supplements sold over the Internet account for only one percent of total dietary supplement sales. Attention paid to a small fraction of Internet supplement marketers who break the law is disproportionate to the actual problem. Nevertheless, the industry has been vocal in its support of the FTC’s Internet sweeps and encourages their continuation. Safety If there were not a presupposition that dietary supplements are inherently unsafe, we would not be here this morning. Therefore, I believe we need to put supplement safety in perspective. Intense media coverage of the relatively rare cases of certain dietary supplements causing injury has resulted in misconception about their safety. The truth is that dietary supplements are far safer than most common foods and drugs that consumers use without a second thought. For instance, a common OTC pain reliever is responsible for more than 17,000 deaths annually.1 Prescription drugs, for all the testing they go through and copious usage directions that are issued with them, are estimated to be one of the top five leading causes of death in the U.S. at more than 106,000 annually.2 And, more than 5,000 Americans die each year from food borne illnesses.3 You may hear statistics this morning from other sources regarding dietary supplements, but let me tell you what the FDA says. According to the agency, it received 1,214 reports of adverse events regarding dietary supplements in 2001.4 (An adverse event is described as being an undesirable experience associated with the use of a product, but not necessarily caused by using the product). There are those who claim this number would be much higher were a different reporting system in place. The FDA has just begun implementing an extensively revamped reporting system for dietary supplements that should yield more accurate data about potential problems with these products and others. This new system should be given a chance to work. The industry supports efforts that will provide a constructive and impartial representation of dietary supplement safety. I believe, however, that reports of adverse reactions to dietary supplements will continue to remain relatively low. In support of this assertion, I would refer to another well regarded source, the American Association of Poison Control Centers. In this group’s most recent report of poison control centers throughout the United States, adverse reactions to drugs are more than 800 percent higher than those for dietary supplements.5 If consumers are expected to make informed decisions about the safety of dietary supplements – or anything else – they deserve to know all the facts. And the facts are that, in addition to providing undisputed health benefits to millions of Americans, dietary supplements are far safer to consume than drugs and most foods. Although it is not the focus of this hearing, we should also not lose sight of the important benefits dietary supplements have on human health. When Congress passed DSHEA it acknowledged that there may be a connection between dietary supplement use, reduced health-care expenses, and disease prevention. In fact, current research is bearing out this very supposition. As examples, the American Medical Association recently reversed its position on the value of taking a daily multivitamin, suggesting that every adult would benefit from a daily multivitamin.6 Not only has research demonstrated the health benefits of dietary supplements, it has also shown that they can reduce health-care costs by the billions of dollars. For example, a study published earlier this month reported that if seniors took a multivitamin daily it could reduce health care costs by $1.6 billion annually.7 Another study in a major medical journal reported that increased intakes of vitamin E, folic acid and zinc could save $20 billion annually in hospital costs by reducing heart disease, birth defects and premature death.8 These are not isolated examples. In summary, DSHEA provided more label information, increased FDA enforcement authority to preserve consumer safety and mandated higher product standards. The result is an increased ability by consumers to make informed personal health choices. But to be effective, like any law, it needs to be implemented and enforced. The bottom line is that there is no issue with dietary supplements, be it safety, efficacy or quality, which cannot be addressed under the current regulatory and legal framework. Finally, I will leave the committee with three recommendations to improve the effectiveness of DSHEA. The first is to give the FDA the resources it needs to fully implement the law. Passage of a new bill introduced in the Senate by Sens. Tom Harkin and Orrin Hatch, S. 1538, would do just that. This bill, “The DSHEA Full Implementation and Enforcement Act,” would provide the FDA with the funding it needs to ensure that DSHEA is carried out as Congress intended. It would also increase funding for the National Institutes of Health’s Office of Dietary Supplements, which was created by DSHEA to expand research and provide consumer information on dietary supplements. The second is for the FDA to quickly finalize and begin enforcement of good manufacturing practices for dietary supplements. Although I believe the vast majority of dietary supplement manufacturers have implemented production procedures that meet or exceed what is currently required by law, a federal GMP regulation would bring all others into line, as well. My final recommendation is this: Stop seeking legislative solutions to regulatory problems when it comes to DSHEA. Changing DSHEA to give the FDA increased authority when it has not fully applied its current powers will simply perpetuate the current situation. * * * * * References 1. Wolfe M. M., Lichtenstein D. R., Singh G.,“Medical Progress: Gastrointestinal Toxicity of Nonsteroidal Anti-inflammatory Drugs,” New England Journal of Medicine 340:1888-1899 (1999). 2. Lazarou, Jason, Pomeranz, Bruce H., Corey, Paul N., “Incidence of Adverse Drug Reactions in Hospitalized Patients: A Meta-analysis of Prospective Studies,” Journal of the American Medical Association 279:1200-1205 (1998). 3. Paul S. Mead, et al, “Food-Related Illness and Death in the United States,” Morbidity and Mortality Weekly Report (Sept.-Oct. 1999). Electronic version available at http://www.cdc.gov/ncidod/eid/vol5no5/mead.htm#Figure%201. 4. U.S. Food and Drug Administration, “FDA Proposes Manufacturing and Labeling Standards for all Dietary Supplements,” backgrounder, March 7, 2003. Electronic version available at http://www.fda.gov/bbs/topics/NEWS/dietarysupp/background.htm. 5. Toby L. Litovitz, at al, “2001 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System,” American Journal of Emergency Medicine, 20, no. 5 (2002). Electronic version available at www.aapcc.org/Annual%20Reports/01report/2001%20TESS%20Full%20Report.pdf. 6. “Vitamins for Chronic Disease Prevention in Adults.” Kathleen M. Fairfield, M.D., Dr.PH.; Robert H. Fletcher, M.D., M.Sc.; Journal of the American Medical Association (June 19, 2002, Vol. 287 No. 3: 3116-3126) 7. “A Study of the Cost Effects of Daily Multivitamins for Older Adults.” DaVanzo JE, Dobson A, Consunji M, Gilani J, McMahon JP, Preston B, Sen N, presented by The Lewin Group October 2, 2003. 8. “Potential Health Economic Benefits of Vitamin Supplementation.” A. Bendich; R. Mallick; S. Leader. Western Journal of Medicine (1997, Vol. 166: 306-312)

• Mr. Terry Madden

  Chief Executive Officer

  U.S. Anti-Doping Agency

• Dr. Arthur Grollman
  Read statement

  Witness Panel 2

  Dr. Arthur Grollman

  In 2001, Americans spent $17.76 billion on dietary supplements, $4.18 billion of which were spent on herbs and other botanical remedies.1 These herbal products have greatly increased in popularity over the past decade, most likely stimulated by the high prices of prescription drugs, restricted access to physicians resulting from managed care procedures, media reports of adverse effects of prescription drugs and, most importantly, enactment in 1994 of the Dietary Supplement and Health Education Act (DSHEA). By broadly defining herbs and other botanicals as “dietary supplements,” which they most assuredly are not, DSHEA significantly changed the rules for evaluating and enforcing claims for effectiveness and safety of these products.2 This inappropriate product classification has resulted in a serious and growing public health problem. The perception that herbal remedies are inherently safe is based primarily on tradition rather than on systematic studies designed to detect adverse effects. Nevertheless, evidence of their toxicity is accumulating3-10. This is not surprising because it is well-established that botanicals are, in fact, “crude drugs of vegetable origin”11 and contain complex mixtures of chemicals, many of which are potentially toxic. In the past year alone, the FDA was compelled to issue warnings of nephrotoxicity (kidney damage), hepatotoxicity (liver damage) and carcinogenicity (cancer development) associated with herbal products containing kava, comfrey and aristolochic acid, all herbal remedies used widely in the US and Europe.5 In addition to their own toxicities9,10, botanical products are associated with other factors that affect their safety; several of these are discussed below. LACK OF STANDARDIZATION The safe and effective use of any medicinal compound requires that each product sold has the same composition and biological activity. Unfortunately, botanical preparations rarely meet these criteria because of problems in identifying the plants, the variability in genetic make-up of the plants, variations in growing conditions, harvesting, and processing of extracts and, above all, the inability to identify active pharmacologic agents within the large number of chemicals present in plants. A few companies have developed methods to standardize herbal preparations, but these techniques do not assure pharmacologic activity or stability. Moreover, chemical analyses of supposedly standardized herbal preparations reveal that many such products do not contain the amount of compound stated on the label.12,13 “Their potency may vary and their purity is suspect,” warns the Medical Letter.3 ADULTERATION OF BOTANICAL PREPARATIONS Many herbal products have been found to contain prescription or over-the-counter drugs and dangerous heavy metals.14-17 In 1998, the California Department of Health reported that 32% of Asian herbal medicines sold in that state contained undeclared pharmaceuticals or heavy metals.15 The drugs most frequently found were ephedrine, chlorpheniramine, methyltestosterone and phenacetin; 10-15% contained lead, mercury and arsenic. Subsequently, more than 500 Chinese herbal medicines were screened for the presence of heavy metals and/or any of 134 selected drugs.16 Approximately 10% were found to contain undeclared drugs and/or toxic levels of metals. The FDA and other investigators17 have also reported the presence of prescription drugs, including glyburide, sildenafil, colchicine, adrenal steroids, alprazolam, phenylbutazone and fenfluramine in products claimed to contain only natural ingredients. One "supplement," PC-SPES, is a patented herbal preparation marketed to enhance “prostate health,” but commonly used to treat prostate cancer. Reports of its effectiveness have appeared in major medical journals.18,19 After chemical analysis of PC-SPES revealed the presence of diethylstilbesterol (an estrogen), indomethacin (an extremely potent nonsteroidal anti-inflammatory drug), and/or warfarin (an anti-clotting drug),18 this product was removed from the market. Recently, the Japanese Ministry of Health, Labor and Welfare reported that the use of certain imported Chinese dietary supplements was associated with liver failure and/or extremely high thyroid function.20 These products proved to be adulterated with drugs and 622 patients became ill, with 148 requiring hospitalization; three deaths occurred.21 The offending products were recalled and the Ministry will henceforth require manufacturers to chemically analyze all imported dietary supplements. All of these cases should be considered as warnings to us about the state of purity of products on our store shelves. It is DSHEA that allows them to be placed there and to stay there. HERB-DRUG INTERACTIONS Interactions between herbal products and prescription or over-the-counter (OTC) drugs constitutes one of the greatest risks posed by the use of botanical remedies. Botanical medicines can act through a variety of mechanisms to alter the actions and metabolism of prescription and OTC drugs.22 St. John’s wort, for example, increases the level of specific enzymes (i.e., the cytochrome P-450 isozyme CYP3A4 and intestinal P-glycoprotein), which leads to a decrease in the blood level of many drugs, including cyclosporine (needed to prevent transplanted organ rejection), antiretroviral agents (needed to keep HIV in check), digoxin (to protect the heart) and warfarin (to prevent blood clotting in patients with certain dangerous clotting conditions).23 In fact, serious adverse effects have been reported in patients taking cyclosporine or antiretroviral agents when they added St. John’s wort, which caused blood levels of their life-saving drug to fall to amounts that were no longer therapeutic. The extent of herb-drug interactions is unclear, but its potential magnitude can be judged by a recent survey of medication use in the U.S.24 Among individuals over the age of 18 years, 50% took at least one prescription drug during the preceding week. Among women 65 years or older, 23% took at least five prescription drugs. Importantly, 16% of people taking prescription drugs also took a herbal/supplement. Thus, many Americans unknowingly risk therapeutic failures or adverse effects due to herb-drug interactions, especially older individuals who take multiple medications for chronic diseases. LACK OF ADVERSE EVENT REPORTING The FDA maintains surveillance of prescription drugs by requiring manufacturers to report promptly to the agency all adverse effects brought to their attention. Even with these requirements, it is estimated that only 10% of serious adverse effects associated with the use of prescription drugs are ultimately reported to the FDA.25 It is fortunate, however, that the manufacturers must demonstrate safety of the prescription drugs in clearly defined clinical trials before the FDA permits the product to be marketed. Unfortunately, such premarket safety testing is not required for dietary supplements and there is no mandatory requirement for manufacturers of supplements to record, investigate or forward to FDA reports of adverse effects they might receive. In addition, although some adverse reactions to botanical medicines are immediate and produce symptoms, others, such as kidney failure and development of cancers, have a delayed and gradual onset and their relationship to earlier consumption of an herbal remedy may not be apparent. This lack of adverse event reporting to the FDA has generated concern at the level of the HHS Office of the Inspector General.25 In 2001, the FDA received approximately 500 reports of adverse events related to dietary supplements, while Poison Control Centers in the United States received 19,468 such reports,26 up from 6914 in 1998. In addition, the FDA often is unable to investigate reports they do receive because the consumer’s identity and address cannot be obtained or the ingredients of the supplement and the identity and address of the manufacturer are unknown. The Inspector General’s report estimates that less than 1% of adverse events caused by dietary supplements, including herbs, are reported to FDA and only a fraction of these are adequately investigated. CURRENT REGULATION OF BOTANICAL MEDICINES Regulation of food and drugs has always been strongly resisted by industry, and Congress has acted only in response to strong pressure from the public. The Food and Drug acts passed in the 20th century to provide important protection to the public, were largely circumvented for dietary supplements by passage of DSHEA. This single piece of legislation negated work conducted over decades to ensure that all medications were studied and evaluated for safety and efficacy before they reached the American public. Importantly, DSHEA freed the dietary supplement industry from effective oversight by the FDA by transferring the burden of proof for establishing herbal medicine safety away from the manufacturer and to the FDA. It is shocking to realize that dietary supplements are now subject to lower safety standards than are food additives and that consumers are provided with more information about the composition and nutritional value of a loaf of bread than about the ingredients and potential hazards of botanical medicines. The way in which restrictions imposed by DSHEA hinder the FDA from promptly removing dangerous products from the market may be appreciated by considering two examples. One clear problem is that posed by the herbal supplement ephedra.. Ephedrine alkaloids are present in many supplements marketed for weight loss and to boost energy. Like their chemical relative methamphetamine, or “speed,” they have powerful stimulatory effects on the cardiovascular and central nervous systems, and their use has been associated with strokes, heart rhythm abnormalities, seizures, acute psychoses, heart attacks and death.27,28 More than 18,000 adverse events related to ephedra have been reported to FDA, including 117 deaths and the actual number of these events undoubtedly is far greater.29 In addition, 33 deaths of military personnel led the U.S Army to ban the sale of ephedra products from its commissaries worldwide.29 Metabolife 346, a product containing ephedra, caffeine and several herbs, is taken by an estimated 12 million Americans. It was revealed recently that 14,480 complaints of adverse reactions had been registered with the company, including 2000 significant adverse events;29 several hundred of these required hospitalization and there were 80 incidents of serious injury or death. Incredibly, under current regulations there is no penalty for withholding reports of adverse effects; nevertheless, the Justice Department, at the FDA’s request, has initiated a criminal investigation of Metabolife because of false statements claiming the absence of adverse effects. Canadian--but not American--health authorities have requested voluntary recall of health products containing ephedra, noting its enhanced toxicity when combined with caffeine.30 Ephedra accounts for 64% of all adverse reactions to herbs in the United States, yet ephedra products represent only 0.82% of herbal product sales.31 A particularly dramatic example of the toxicity of herbal products is the kidney failure and subsequent kidney cancer caused by Aristolochia fangchi, used for centuries in Europe and China as an herbal remedy. The clinical toxicity of A. fangchi was recognized in 1991 when this herb was substituted for another in a weight loss preparation used in a Belgian health spa. 6,32 Of 105 patients affected by this herb who developed kidney disease (and treated in one medical center), 39 with end-stage kidney failure decided to have their kidney removed completely because of concerns about developing kidney cancer. Indeed, actual carcinomas were found in 18 of these patients and a precancerous condition (urothelial dysplasia) in 19 others.33 This syndrome, aristolochic acid nephropathy, was also found in patients in other countries, including the United States. 6 As a result of warnings issued by the FDA, a number of herbal products containing aristolochic acid were withdrawn from the market in 2001. Importantly, the names of these products, such as Joint Ease, and Balance and Harmony, contained no information suggesting the presence of aristolochic acid, which had, nevertheless, been documented to be toxic to the kidney and carcinogenic in rats.34 Even today, 19 products containing aristolochic acid and 95 products suspected to contain aristolochic acid can purchased over the Internet.35 NEW REGULATIONS ARE NEEDED Public awareness of the hazards of dietary supplements has increased in recent years and a majority of Americans now support legislation (a) requiring the FDA to review the safety of new dietary supplements prior to their sale; b) providing increased authority for the FDA to remove unsafe products from the market; and c) regulating advertising claims about the health benefits of dietary supplements.36 However, for the FDA to effectively carry out its mandate to protect public health, new legislation and resources are required. The legislative proposals outlined below could accomplish this goal without denying consumers access to this popular class of products. 1) The address and telephone numbers of all companies, as well as the names of the responsible persons, involved in manufacturing dietary supplements for sale in the U.S should be directly registered with FDA. Currently, the FDA is severely limited in its efforts to investigate adverse effects of dietary supplements because of the lack of information about manufacturers and distributors. 2) Manufacturers of dietary supplements must provide evidence of good manufacturing practices (GMP) and the FDA should be given the authority to inspect manufacturers’ records. In 1999, the FDA held public meetings and published an advance notice of proposed regulations that address this issue. Implementation of even this proposal has been blocked by the botanical industry. Such an extension of GMP to herbal manufacturers could go far toward preventing adulteration and ensuring standardization of marketed botanical products. 3) Congress should require manufacturers of dietary supplements to report all adverse effects to the FDA to ensure identification of potential public health problems as quickly as possible. Postmarketing surveillance is an essential element of this proposed legislative reform. Serious adverse effects should be reported to FDA promptly; others should be reported on a quarterly basis. CFSAN's Adverse Event Reporting System ("CAERS") provides a mechanism for consumers and health care providers to report adverse events or illness thought to be related to the use of a dietary supplement. Congressional appropriations should continue to fund this system, which facilitates tracking and analysis of adverse events associated with dietary supplements. However, complete reporting information from all sources, including manufacturers, is required to ensure prompt and accurate identification of potential public health problems. Once FDA identifies a potential problem, it should notify the manufacturer who would then be required to respond to FDA within 30 days and to conduct discussions with FDA regarding appropriate corrective action. 4) The burden of proof for demonstrating that a dietary supplement does not present a “significant or unreasonable risk of illness or injury under conditions of recommended use, as suggested on the label”, should be placed on the manufacturer. Under DSHEA, the FDA must carry the burden of proving “significant or unreasonable risk” before it can remove a dangerous product, such as aristolochic acid or ephedra, from store shelves. Manufacturers should be required to provide evidence of safety either when a new product is introduced or when serious adverse effects are uncovered from the sale of an existing product during postmarketing surveillance. As the manufacturers benefit from product sales, they should also pay the costs of conducting appropriate safety testing, as required for prescription and over the counter drugs. FDA does not have the resources nor the infrastructure to conduct safety testing for the multitude of marketed dietary supplements, and testing can be conducted more efficiently using the manufacturer's extensive knowledge of its own product. 5) Dietary supplements should carry labels containing a list of constituents that clearly and unambiguously identifies herbs by their botanical and common names. If pharmacologically active principle(s) are known, the concentration of such substances should appear on the label. Information regarding possible adverse effects, including the potential for herb-drug interactions, should be included in the information provided to the consumer. 6) The Department of Health and Human Services should organize expert panels to review the safety of all dietary supplements, except for essential nutrients and single and multivitamin preparations. This process should be modeled after the National Academy of Sciences Drug Efficacy Study, which completed the complex task of evaluating the safety and efficacy of 4000 drugs in just three years. CONCLUSIONS The medical community has been slow to respond to the public health issues and educational problems resulting from the weakened regulation of dietary supplements.37 However, the numerous reports of adverse effects and deaths associated with botanical health products, the easy distribution and widespread sale of adulterated products, and a marked increase in misleading promotional claims via the Internet demand prompt action to protect the public health. The European Parliament currently is considering measures to ensure that all traditional herbal medicinal products used in member countries demonstrate efficacy and an acceptable level of safety.38 The legislative reforms that I am proposing here will be opposed by powerful political and economic forces2,39 and by many proponents of complementary and alternative medicine. Nevertheless, Congress should stand up for the public health, recognize the critical need for new regulatory safeguards, and ensure additional government funding to carry them out. It is time that the public health interest superseded that of the botanical industry.