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81–314 PDF 2002

S. Hrg. 107–619

WHEN DIETS TURN DEADLY: CONSUMER SAFETY

AND WEIGHT-LOSS SUPPLEMENTS

HEARING

BEFORE THE

OVERSIGHT OF GOVERNMENT MANAGEMENT,

RESTRUCTURING, AND THE DISTRICT OF COLUMBIA

SUBCOMMITTEE

OF THE

COMMITTEE ON

GOVERNMENTAL AFFAIRS

UNITED STATES SENATE

ONE HUNDRED SEVENTH CONGRESS

SECOND SESSION

JULY 31, 2002

Printed for the use of the Committee on Governmental Affairs

(

(II)

COMMITTEE ON GOVERNMENTAL AFFAIRS

JOSEPH I. LIEBERMAN, Connecticut, Chairman

CARL LEVIN, Michigan

DANIEL K. AKAKA, Hawaii

RICHARD J. DURBIN, Illinois

ROBERT G. TORRICELLI, New Jersey

MAX CLELAND, Georgia

THOMAS R. CARPER, Delaware

JEAN CARNAHAN, Missouri

MARK DAYTON, Minnesota

FRED THOMPSON, Tennessee

TED STEVENS, Alaska

SUSAN M. COLLINS, Maine

GEORGE V. VOINOVICH, Ohio

THAD COCHRAN, Mississippi

ROBERT F. BENNETT, Utah

JIM BUNNING, Kentucky

PETER G. FITZGERALD, Illinois

JOYCE A. RECHTSCHAFFEN, Staff Director and Counsel

RICHARD A. HERTLING, Minority Staff Director

DARLA D. CASSELL, Chief Clerk

OVERSIGHT OF GOVERNMENT MANAGEMENT, RESTRUCTURING, AND

THE DISTRICT OF COLUMBIA SUBCOMMITTEE

RICHARD J. DURBIN, Illinois, Chairman

DANIEL K. AKAKA, Hawaii

ROBERT G. TORRICELLI, New Jersey

THOMAS R. CARPER, Delaware

JEAN CARNAHAN, Missouri

MARK DAYTON, Minnesota

GEORGE V. VOINOVICH, Ohio

TED STEVENS, Alaska

SUSAN M. COLLINS, Maine

THAD COCHRAN, Mississippi

PETER G. FITZGERALD, Illinois

MARIANNE CLIFFORD UPTON, Staff Director and Chief Counsel

MELANIE LEITNER, Congressional Fellow, Senator Durbin

ANDREW RICHARDSON, Minority Staff Director

THERESA PRYCH, Minority Professional Staff Member

BRIAN MCLAUGHLIN, Staff Assistant

(III)

C O N T E N T S

Opening statement: Page

Senator Durbin ................................................................................................. 1

Prepared statement:

Senator Voinovich ............................................................................................. 39

WITNESSES

WEDNESDAY, JULY 31, 2002

Janet Heinrich, Director, Health Care—Public Health Issues, U.S. General

Accounting Office ................................................................................................. 4

Michael F. Mangano, Principal Deputy Inspector General, Office of Inspector

General, Department of Health and Human Services ...................................... 6

Joseph A. Levitt, Esq., Director, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Department of Health and Human

Services; accompanied by Dr. Christine Lewis Taylor, Director, Office of

Nutritional Products, Labeling and Dietary Supplements (ONPLDS), Center

for Food Safety and Applied Nutrition (CFSAN), and John Taylor, Director,

Office of Enforcement, Office of Regulatory Affairs (ORA), Food and Drug

Administration (FDA) .......................................................................................... 8

Karen Ruiz, Consumer, San Clemente, California ............................................... 19

Steven B. Heymsfield, M.D., Deputy Director, New York Obesity Research

Center, St. Luke’s-Roosevelt Hosptial Center, Professor of Medicine, Columbia University, College of Physicians and Surgeons ......................................... 22

Michael McGuffin, President, American Herbal Products Association (AHPA),

Silver Spring, Maryland ...................................................................................... 25

Cynthia T. Culmo, R.Ph., Chairperson, Drugs, Devices, and Cosmetics Committee, Association of Food and Drug Officials, Austin, Texas ........................ 27

ALPHABETICAL LIST OF WITNESSES

Culmo, Cynthia T., R.Ph.:

Testimony .......................................................................................................... 27

Prepared statement with attachments ........................................................... 160

Heinrich, Janet:

Testimony .......................................................................................................... 4

Prepared statement with attachments ........................................................... 40

Heymsfield, Steven B., M.D.:

Testimony .......................................................................................................... 22

Prepared statement with attachments ........................................................... 123

Levitt, Joseph A., Esq.:

Testimony .......................................................................................................... 8

Prepared statement .......................................................................................... 86

Mangano, Michael F.:

Testimony .......................................................................................................... 6

Prepared statement with attachments ........................................................... 65

McGuffin, Michael:

Testimony .......................................................................................................... 25

Prepared statement .......................................................................................... 139

Ruiz, Karen:

Testimony .......................................................................................................... 19

Prepared statement .......................................................................................... 118

APPENDIX

‘‘Code of Ethics & Business Conduct,’’ June 2002, submitted by Mr. McGuffin 146

Page

IV

‘‘Ephedra-containing Supplements Produced by Members Of Leading Trade

Association Test Well in New Study,’’ May 19, 2000, submitted by Mr.

McGuffin ............................................................................................................... 157

Consumer Healthcare Products Association (CHPA), prepared statement ........ 191

John Hathcock, Ph.D., Vice President, Nutritional and Regulatory Science,

Council for Responsible Nutrition (CRN), prepared statement ........................ 195

Raymond L. Woosley, M.D., Ph.D., Vice President for Health Sciences, University of Arizona, prepared statement .............................................................. 197

(1)

WHEN DIETS TURN DEADLY: CONSUMER

SAFETY AND WEIGHT-LOSS SUPPLEMENTS

WEDNESDAY, JULY 31, 2002

U.S. SENATE, OVERSIGHT OF GOVERNMENT MANAGEMENT, RESTRUCTURING, AND THE DISTRICT OF COLUMBIA SUBCOMMITTEE, OF THE COMMITTEE ON GOVERNMENTAL AFFAIRS, Washington, DC.

The Subcommittee met, pursuant to notice, at 10:01 a.m., in

room SD–342, Dirksen Senate Office Building, Hon. Richard Durbin, Chairman of the Subcommittee, presiding.

Present: Senators Durbin and Voinovich.

OPENING STATEMENT OF SENATOR DURBIN

Senator DURBIN. I would like to welcome everyone to the hearing

this morning. We will get under way, and I note people are still

coming in. They are welcome to find a seat, since they are available. I would like to advise you that we anticipate some votes

around 11 o’clock, so I am hoping that we can complete opening

statements and the first panel. Then perhaps take a break for the

voting, and return to complete the hearing.

I am pleased to welcome you to today’s hearing before the Senate

Subcommittee on Oversight of Government Management, focusing

on ‘‘When Diets Turn Deadly: Consumer Safety and Weight-Loss

Supplements.’’

There may be some argument across America about whether the

great American pasttime is baseball. Last year nearly 50 million

people attended a major league baseball game, but 100 million

Americans are on a diet. It appears that we have spent a lot of our

time as Americans thinking about weight loss. According to the

Centers for Disease Control and Prevention, 25 percent of adult

men, 40 percent of adult women, and an even higher percentage of

teenagers are currently trying to lose weight. Some will be inspired

by medical professionals to follow a diet and exercise. Others will

be convinced by infomercials to buy the latest exercise video or

magic machine. Many will look for a pill to help make the pounds

disappear.

The purpose of this hearing is not to announce the new congressional diet or endorse the latest ab cruncher. The Federal Government should leave that to others. But there is one area of weight

loss where the government, particularly the Food and Drug Administration, does have responsibility. Americans count on the FDA to

make sure the drugs and nutritional supplements they take are

safe. When it comes to drugs, the law is clear: no drug can be leVerDate 11-MAY-2000 12:52 Jan 16, 2003 Jkt 000000 PO 00000 Frm 00005 Fmt 6633 Sfmt 6633 81314.TXT SAFFAIRS PsN: SAFFAIRS
2

gally sold in America until the FDA certifies it is both safe and effective. This certification involves extensive testing before a drug

comes to market, and after it has come to market, monitoring of

that drug and its consequences.

But when it comes to dietary supplements, everything from vitamins, minerals, herbal components, steroid precursors, animal derivatives and weight-loss supplements, we have a different standard. The Dietary Supplement Health and Education Act of 1994

said that in most cases supplements are considered safe. There is

a presumption of safety. The product can be sold until the FDA can

prove that it is unsafe.

Let me inject a personal note here, so that if there is any question in your mind. When I got up this morning, I took my vitamin.

I believe in them. I think people should have the right to make

that choice, to take the vitamins and minerals that they think are

important to their personal health. We are not calling for the sale

of vitamins by prescription. That is not what this hearing is about.

But the reason that we are holding this hearing is because there

have been several events recently, when it comes to dietary supplements, which have caught everyone’s attention.

On January 9 of this year the Canadian Government issued a

warning about a particular class of supplements containing the

herb ephedra, sold for the purpose of weight loss. It is also sold for

body building and to increase energy. The Canadian Government

advised the people of Canada to avoid these products because they

may, ‘‘cause serious, possibly fatal adverse effects,’’ when combined

with caffeine or other stimulants. They announced reports of adverse health events involving these drugs, which range from dizziness to tremors, headaches, irregular heart rates, seizures, psychoses, heart attacks and stroke. Health Canada then issued a voluntary recall of these products containing ephedra or ephedrine nationwide. Many of the ephedra supplements recalled by the Canadian health authorities can be found today on the shelves of stores

across America.

Canada is not alone. A variety of athletic organizations including

the International Olympic Committee, the National Football

League and the National Collegiate Athletic Association have

banned a variety of dietary supplements, including—and forgive

me if I mispronounce this, I am a liberal arts lawyer—androstenedione, known as ‘‘andro’’ from this point forward in the hearing, a steroid precursor, and the weight-loss product ephedrine.

Despite this ban, a 2001 NCAA study of ergogenic compounds,

compounds that increase work output, found that 4 percent of the

21,000 athletes that completed the confidential survey have used

ephedrine in the past 12 months. Even more disturbing, this number had increased since the ban went into effect in 1997, especially

among women’s teams. According to the study most athletes reported using ergogenic products started in high school.

The obvious questions are these: Whether the health concerns

announced by Canada and athletic organizations in our country

about ephedra supplements are valid? What action should be taken

by the Department of Health and Human Services and the Food

and Drug Administration in light of the Canadian recall, and

whether the 1994 law which Congress enacted, protects American

3

1The slide appears in the Appendix on page 77.

2The slide appears in the Appendix on page 78.

consumers from supplements that may be dangerous to their

health?

At this hearing we will ask these and other questions about

whether the 1994 law is working when it comes to weight-loss supplements. The GAO, General Accounting Office, will tell us about

the analysis they just completed about the safety and regulation of

this industry. The Inspector General’s Office and the Department

of Health and Human Services will tell us about a report they

turned in on the warning system that exists for problems with dietary supplements, and we will ask the Food and Drug Administration whether the current system is working to protect Americans

from dangerous health results. We will hear from a woman who

took one of those supplements, with a very negative health consequence. We will hear from a doctor who studies weight loss. We

will hear from a spokesman for the trade organization representing

the supplement industry, as well as public health officials, who

have attempted to increase the standard of supplement regulation

in their State. I might add that some 21 States or more have imposed stricter regulation on the sale of these supplements than is

required by the Federal Government.

To put this issue in some context, I want to first share some information on the supplement industry. There has been an explosion

in the sale of dietary supplements since the 1994 law was enacted.

As you can see from this slide,1 the supplement industry is currently estimated to be on track to have $19 billion in sales in the

year 2002. They have more than tripled their sales since the passage of the Federal law. Weight-loss products account for a significant part of supplement sales. So what do some of these weightloss supplement manufacturers tell the consumers about their

products? Here is an example of a supplement product produced by

a company that has been in the supplement business for 20 years.

I know it is a little hard to read, but it is a product called Pure

Ephedrene. How is the consumer to distinguish between ephedra,

which is marketed as an herbal product, and ephedrine HCl which

is an over-the-counter drug, especially as ephedrine alkaloids are

the active ingredients found in ephedra? I am not sure.

What kind of language is used to sell Pure Ephedrene? 2 Well, it

says, ‘‘Pure Ephedrene is available all the time and in unlimited

quantities, so you can have as much as you want whenever you

want it.’’ This is a strange claim for an all natural herbal product

that is known to be a stimulant, especially given the fact that the

safety range the industry claims for ephedrine alkaloids is 25 milligrams per individual dose up to a maximum of 100 milligrams a

day, and the amount of ephedra per tablet in Pure Ephedrene appears to be 325 milligrams. Allow me to put this in perspective.

The Canadian Government has said that they have a much different dosage level, 8 milligrams per dose, no more than 32 milligrams a day. If we read this warning label or advisory correctly in

this particular advertisement, they are offering a product that offers in one dose 10 times what the Canadians say is a safe daily

dose in four separate dosages.

4

1The slide appears in the Appendix on page 81.

2The prepared statement of Ms. Heinrich with attachments appears in the Appendix on page

40.

The next slide is an example of a current warning label on a topselling weight-loss product containing ephedra and caffeine.1 And

here is what it says: ‘‘This product is for adult use only, and should

not be used by pregnant or nursing women or by anyone with any

known medical condition.’’ What does that mean? What does it

mean to the consumer? While ephedrine and caffeine combinations

were banned by the FDA in 1983 for over-the-counter medications,

many weight-loss supplements contained ephedra and some herbal

form of caffeine, the combination, incidentally, which the Canadians have found to be highly dangerous.

I am looking forward to our witnesses to help us understand this

issue and the responsibility we have to protect the health of American consumers, and at the close of the hearing I will make an announcement concerning some action which I believe that we should

be taking on Capitol Hill.

Let me at this point welcome the first panel of witnesses. Janet

Heinrich is the Director for Health Care—Public Health Issues

with the General Accounting Office. Her office has produced several

reports relating to dietary supplements, including a recent report

titled ‘‘Health Products for Seniors, Potential Harm from AntiAging Products.’’ I am going to look for that one too.

Second is Dr. Michael Mangano. He is the Principal Deputy Inspector General within the Office of the Inspector General for the

Department of Health and Human Services. Thank you.

Finally, Joseph Levitt, who is the Director of the Center for Food

Safety and Applied Nutrition within the Food and Drug Administration.

We thank you for coming this morning. It is customary for the

Subcommittee to swear in all witnesses. Therefore I would like to

ask you to stand and please raise your right hand.

Do you swear that the testimony you are about to give is the

truth, the whole truth and nothing but the truth, so help you, God?

Ms. HEINRICH. I do.

Mr. MANGANO. I do.

Mr. LEVITT. I do.

Senator DURBIN. Let it be noted for the record that the witnesses

answered in the affirmative. We have your statements, and I have

a number of questions which I would like to ask, and I would ask

you if you would please summarize your statements in about 5

minutes. We will not hold you to that exactly. And then I will proceed with some questions.

Ms. Heinrich, would you like to start?

TESTIMONY OF JANET HEINRICH,2 DIRECTOR, HEALTH

CARE—PUBLIC HEALTH ISSUES, U.S. GENERAL ACCOUNTING

OFFICE

Ms. HEINRICH. Mr. Chairman, I am pleased to have the opportunity to testify as the Subcommittee considers concerns about dietary supplements that are used for weight loss.

As you said, U.S. sales of weight-loss supplements have increased steadily. It is estimated that Americans spent almost $2

5

billion in weight-loss supplements in 2001. Obesity in the United

States is reported to be a growing epidemic, and many people are

trying to lose weight.

As sales of weight-loss supplements have increased so have concerns associated with their marketing and use. Because of these

concerns, you asked us to examine the safety and efficacy of

weight-loss supplements, Federal oversight, research, and public

education efforts, and State and local regulatory efforts aimed at

consumer protection of these products.

For most weight-loss supplements there is little scientific evidence to support their efficacy. Although there have been studies

on specific ingredients, many of these studies were of short duration, involved small numbers of individuals, or use study approaches that limit the usefulness of their findings.

There has been limited Federal research on weight-loss supplements. The Office of Dietary Supplements at the National Institutes of Health is working with other Federal agencies to develop

a research agenda. However, none of the institutes and centers

have made weight-loss supplements a priority at this time. Available research, again limited, also suggest that some supplements

are associated with harmful side effects. Some side effects are

minor, such as indigestion or rash, while others are very serious.

For example, DHEA, a hormone associated with reduction in fat

deposits may increase the risk of breast cancer. And ephedra, as

you suggest, has been associated with seizures, heart attacks, and

stroke. Supplements also may be contraindicated for individuals

with certain medical conditions or may have dangerous interactions

with prescription and over-the-counter drugs.

The amounts of active ingredients can vary from what is indicated in a product label. Products sometimes contain ingredients

not listed on the label, or may have as many as 22 active ingredients, all listed on the label, but with amounts unknown if the product contains a proprietary blend. Studies have also found supplements contaminated with pesticides or heavy metals known to

damage the liver and kidneys.

The Food and Drug Administration, FDA, and the Federal Trade

Commission, FTC, have oversight responsibilities for safety and

marketing. FDA has been hindered in its ability to address safety

concerns with weight-loss supplements by weaknesses in its Adverse Event Reporting System, as well as the lack of scientific evidence from clinical trials.

Senator DURBIN. Can I interrupt you for a second? Would you explain what Adverse Event Reporting means?

Ms. HEINRICH. What that means is that on a voluntary basis, individuals or health care providers, can turn in information about

medical conditions that they think are associated with a particular

product. FDA has an Adverse Event Reporting System for all drugs

as well as for dietary supplements.

Senator DURBIN. Thank you.

Ms. HEINRICH. Difficulty in obtaining and properly documenting

these voluntary Adverse Event Reports has been a major problem

in the past. Even with Adverse Event Reports, FDA’s ability to respond is different for dietary supplements than for drugs. Dietary

supplements are regulated more like foods, and FDA must meet a

6

1The prepared statement of Mr. Mangano with attachments appears in the Appendix on page

65.

higher safety threshold to take regulatory action than for drugs

that contain similar ingredients. While it is reasonable to assume

that foods are safe, many supplements are more like synthetic

drugs.

FDA and FTC have taken enforcement actions against manufacturers for improper labeling and false advertising. FDA has taken

16 actions since 1995 against manufacturers of dietary supplements marketed with weight-loss claims almost entirely for products that are improperly labeled as dietary supplements. For example, in 2001 FDA took action against the manufacturer of AMP II

Pro drops, an unapproved drug product that contained ephedrine

for a non-herbal source, but was labeled as a dietary supplement.

FTC has taken legal action in 30 cases involving weight-loss substances in this time period. For example, in 2000 Enforma Natural

Products agreed to a settlement with FTC regarding the products

Fat Trapper and Exercise in a Bottle for deceptive claims such as

‘‘You can eat what you want and never have to diet again.’’ FDA does have authority over good manufacturing practices, the

GMPs, which could help in oversight of product dosage and contamination issues. FDA drafted GMP regulations for dietary supplements in 1997, but has been slow to finalize these regulations.

GMPs would standardize manufacturing, packaging and holding

practices, and improve FDA’s enforcement capabilities since the

law provides that dietary supplements not manufactured under

conditions that meet GMPs would be considered adulterated.

In summary, Federal activities related to weight-loss supplements have focused on oversight of marketing more than safety.

Federal activity has focused less on safety in part because of the

lack of scientific evidence and the weaknesses in the voluntary reporting system for adverse events. For FDA regulatory action there

is a different standard of proof requiring a determination that a

supplement causes significant or unreasonable risks. Further research on the efficacy and safety of dietary supplements is needed

to guide consumers choice, especially as the upward trend in sales

and use is expected to continue.

Mr. Chairman, that completes my statement. I am happy to answer any questions.

Senator DURBIN. Thank you. Mr. Mangano.

TESTIMONY OF MICHAEL F. MANGANO,1 PRINCIPAL DEPUTY

INSPECTOR GENERAL, OFFICE OF INSPECTOR GENERAL,

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Mr. MANGANO. Thank you, Mr. Chairman. I appreciate this opportunity to share with you the results of the work we have done

on taking a look at the FDA’s Adverse Event Reporting System for

the dietary supplements.

Unlike prescription drugs, the FDA lacks the authority to require

dietary supplements to undergo premarket approval for safety and

efficacy. Rather, they have to rely extensively on the Adverse

Events Reporting System to give them signals of product problems

with consumer safety. Our review found, however, that the Adverse

7

Event Reporting System for dietary supplements was inadequate

as a safeguard to protect consumer safety. We believe it is so because it has three major weaknesses. The first, the system detects

relatively few adverse events. Like most Adverse Event Reporting

Systems, it is a passive system, requiring somebody with an adverse event to link that event with the use of a dietary supplement

and then report it to the appropriate authorities. Our study confirmed an earlier review that the FDA commissioned, which found

that very few adverse events are ever reported for dietary supplements.

In our study we found that from 1994 through 1999, only a little

over 2,500 adverse events had ever been reported relating to dietary supplements. As a comparison, in the year 1999 the Food and

Drug Administration received about 460 adverse events on dietary

supplements. Over the same time period, the same year, the Poison

Control Centers received over 13,000 reports related to dietary supplements.

The second weakness the FDA has with its Adverse Event Reporting System is its difficulty in generating signals that there may

be a public problem with regard to a particular dietary supplement.

The FDA lacks sufficient information such as consumer medical

records, product ingredients and the identity of manufacturers so

as to analyze the reported events and determine if they raise concerns regarding the public health.

For example, we found that FDA could not obtain medical

records for over half of the Adverse Event Reports where they had

actually requested those records. With regard to product information, FDA was unable to determine the ingredients of one third of

the dietary supplements that were indicated in an Adverse Event

Report, and they had no product label information for three-quarters of the supplements that appeared in those Adverse Events Reports.

So the agency really needs those labels in order to determine the

supplement ingredients and whether they should take action in the

future. Manufacturers have information that would also be very

important for FDA to have regarding these supplements, yet they

could not identify even the manufacturer for one-third of the products in the Adverse Events Reports. Finally, the database housing

the Adverse Event Reports was wholly inadequate for analysis purposes.

The third weakness of the Adverse Event Reporting System is

that sufficient information is not available to assess whether action

is actually required by the FDA to protect public safety. FDA relies

very heavily on clinical research, scientific literature and laboratory testing to assess signals generated by the system, but because

supplement manufacturers are not required to conduct those clinical trials, little of this information is actually known.

The FDA lacks information on the size of the consumer population actually taking the dietary supplements and the dosage

amounts they’re taking. And as mentioned earlier, they suffer from

too few Adverse Event Reports, inadequate Adverse Event Reports,

and a limited computerized database to help them facilitate the

analysis of that data.

8

1The prepared statement of Mr. Levitt appears in the Appendix on page 86.

We estimate that FDA’s taken about 32 actions between 1994

and June 2000, and the two most common were voluntary product

recalls and warnings to consumers.

We recognize, however, that FDA faces significant legislative and

resource barriers to improving the Adverse Event Reporting System.

Our report offers a number of recommendations. I’ll highlight

just a few here this morning. We believe that FDA should seek authority to require manufacturers to report serious adverse events

for some products, require manufacturer and product registration,

contract with the Poison Control Centers to obtain their data and

develop a new computerized database that helps track and analyze

Adverse Event Reports.

I am pleased to say that FDA has recently reported to us that

they have taken a number of those recommendations and put them

into action.

Mr. Chairman, millions of consumers take supplements every

day without any apparent problems and do receive health benefits.

However, risks do exist, and the consumers need to be protected.

This completes my oral testimony. I will be happy to answer any

questions at the appropriate time.

Senator DURBIN. Thanks a lot.

Our next witness is Joseph Levitt with the Food and Drug Administration. Please proceed.

TESTIMONY OF JOSEPH A. LEVITT, ESQ.,1 DIRECTOR, CENTER

FOR FOOD SAFETY AND APPLIED NUTRITION, FOOD AND

DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND

HUMAN SERVICES, ACCOMPANIED BY DR. CHRISTINE LEWIS

TAYLOR, DIRECTOR, OFFICE OF NUTRITIONAL PRODUCTS,

LABELING AND DIETARY SUPPLEMENTS (ONPLDS), CENTER

FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN), AND

JOHN TAYLOR, DIRECTOR, OFFICE OF ENFORCEMENT, OFFICE OF REGULATORY AFFAIRS (ORA), FOOD AND DRUG ADMINISTRATION (FDA)

Mr. LEVITT. Thank you very much, Mr. Chairman. It’s a pleasure

to be here. Let me first introduce two colleagues that are here with

me. The first is Dr. Christine Taylor, Director of our Office of Nutritional Products, Labeling and Dietary Supplements in the Center I direct. And the second is John Taylor, Director of the Office

of Enforcement, Office of Regulatory Affairs at the FDA level, so

he has responsibility across all the regulated products.

I would summarize my testimony, Mr. Chairman, with five main

points. Point No. 1, with which I think everybody here will agree,

is that dietary supplements present a significant challenge worthy

of our attention. As you pointed out, Mr. Chairman, in your opening statement, there is widespread use in this country of dietary

supplements, clearly increased since passage of DSHEA in 1994,

and DSHEA looks to FDA to step in if there is a problem and to

be vigilant on behalf of the public. We welcome reports from GAO,

IG, and others that can help us meet this challenge.

9

Point No. 2 is we do have a plan. We spent, in fact, an entire

year developing a strategic plan on how we would implement

DSHEA. I have a copy here, and copies have been provided to the

Subcommittee. The goals of this plan are clear. We need to fully

implement this law. In doing so we need to provide consumers with

a high level of confidence in the safety, composition, and labeling

of these products. We need to do so in a science-based way, consistent with all of FDA’s successful programs, and we need to recognize that implementation of this law is going to take sustained

time and effort.

Now, we developed this plan with broad public import and support. The major theme we heard from stakeholders was safety first.

As you’ve already heard, look at the Adverse Event Reporting System, make it functional, develop good manufacturing practices, get

them implemented, but I will also tell you that fundamentally, long

term, this program will not be successful unless there is a much

stronger scientific underpinning to the products, and I think that

has been reinforced by both speakers already.

Point No. 3. Congress has asked us what it would take resourcewise to implement the strategic plan, and I am pleased to say that

we submitted a report to Congress this past May which outlines

that. That report concludes that our needs would be in the range

of $40 to $65 million over 5 years. That would be compared to $9

million that we had allocated in fiscal year 2002, the current fiscal

year we’re in. The plan also describes how we would prioritize

those resources, how we would implement them over time, starting

with safety issues, moving on to inspectional issues, and so forth.

I think the bottom line is, you’ll agree, that it does take time,

money and people to operate and implement an effective program.

Point No. 4. We are making progress, admittedly incrementally.

Each year across our entire center we publish our annual priorities

for what we accomplish, or intend to accomplish that year. One section of that report includes dietary supplements. And at the end of

each year, we publish our report on what we have been able to accomplish, and we have been averaging a good 85 to 90 percent completion rate of what we set out to accomplish. We’re also pleased

that Congress has started to appropriate funds earmarked for dietary supplements. We’ve received funds recently in the area of Adverse Event Reporting and academic collaborations on the sciencebased and on enforcement, and we are seeing progress in each of

these areas. We also were able to fund a study to be conducted by

the National Academy of Sciences Institute of Medicine to develop

a framework for evaluation of the safety of dietary supplements,

and you may have seen some press this week on an interim report

from that group. My testimony also outlines a number of enforcement actions which we have taken.

Point No. 5 though, again of which I think every speaker will

agree, we have a lot more to do in this area. As just one example,

on the product ephedra that you have mentioned, Secretary Tommy

Thompson issued a statement in June which outlined a two-prong

approach. Prong one is that we need better research. There is an

ongoing evidence-based review being conducted by the Rand Corporation under the auspices of the NIH to determine what is

known about ephedra and what research needs to be done, and

10

that the NIH is committed, the Department is committed to using

that report as a guide to future research needs.

Concurrently FDA has already initiated a number of enforcement

actions against products that are synthetic ephedrine, and therefore they’re not botanical and they fall outside the scope of DSHEA.

Summarizing then and wrapping up with my five main points,

dietary supplements, of which weight-loss supplements are an important part, and probably illustrative of the broader group of herbal supplements at large, presents significant challenges, something

we clearly need to devote our attention to. Point 2 is that FDA has

developed a strategic plan on a blueprint of how we would implement this with broad stakeholder import and support. No. 3, we

thank Congress for asking for our funding needs, and we have

issued that report. No. 4, we are making incremental progress consistent with the resources that have been allocated. And No. 5, we

recognize this as a long-term effort. There’s a lot more we have to

do. We welcome the input you have, the visibility this hearing provides to helping us achieve those goals.

Thank you very much, Mr. Chairman. I know in your letter of

invitation you had a number of specific questions, and I’ll be happy

to try and answer those during the question period.

Senator DURBIN. Great. Let us start with a few questions, and

some of these are very basic, but I think we ought to put them on

the record.

From the Food and Drug Administration’s viewpoint, is it safe to

say that the chemical properties of ephedrine can be found in a variety of ways in both natural, botanic sources as well as synthetic

sources?

Mr. LEVITT. That’s right.

Senator DURBIN. And is it also true that the Food and Drug Administration, over the years, has regulated the synthetic sources of

ephedrine and how they can be sold in America?

Mr. LEVITT. Yes.

Senator DURBIN. For prescription drugs as well as over-thecounter?

Mr. LEVITT. Yes.

Senator DURBIN. Is it also true that when it comes to the combination of ephedrine with, for example, either a stimulant or an

analgesic, that there have been limitations on the products that

can be offered for sale as prescription drugs and as over-thecounter products?

Mr. LEVITT. I think any product that is regulated as a pharmaceutical, whether it’s as a prescription or as an over-the-counter

drug under our monograph system, regulated by another part of

FDA, not the part I direct, that there are boundaries associated

with claims, with dosages and so on and so forth.

Senator DURBIN. But in terms of the limitation of sale, are there

any forms of ephedrine that have been prohibited by the FDA from

sale, either as an over-the-counter drug or as a prescription drug?

Mr. LEVITT. Well, the history is such—I’m not sure I can answer

that with the specificity you’re looking for—but any time there’s a

monograph that lists the boundaries, and so anything outside that

boundary is not permitted.

11

Senator DURBIN. And so from the consumers’ point of view, if the

Food and Drug Administration has decided that when ephedrine is

in a drug, a prescription drug, or in an over-the-counter product,

that it has to have some limitations in terms of how it can be prescribed and dosage and that sort of thing. From the consumers’ point of view, that same drug could be available through a supplement in a botanical form without the FDA limitations.

Mr. LEVITT. The one distinction I would draw, as we have pointed out, if an ephedrine product is a synthetic-derived product, then

that product is not permitted to come under the dietary supplement provisions. Ephedra comes under the part of the definition of

dietary supplements for botanicals.

Senator DURBIN. Understood.

Mr. LEVITT. So if there is synthetic derived—and I think you’ll

find that a lot of the pharmaceutical products that you’re referring

to are synthetic derived——

Senator DURBIN. I understand that. This is really basic. I go into

my neighborhood drugstore in Springfield, Illinois, and I look at

the pharmacy and I look at what is on the shelf. And I know that

if I am going to get some form of ephedrine through a prescription

drug, I need a doctor’s prescription, and the pharmacy will fill it

with instructions on how I am to take it.

Mr. LEVITT. Right, for certain uses.

Senator DURBIN. I also know if there is an over-the-counter drug

for sale there, according to the FDA, it is going to have instructions

on the back of it as to dosage, contraindications, warnings and that

sort of thing.

Mr. LEVITT. That is correct.

Senator DURBIN. If I move——

Mr. LEVITT. There is now a new standardized format for that

which is very good.

Senator DURBIN. Then I move to the third counter and I see a

dietary supplement. It contains the same drug. Maybe it is called

ephedra, maybe it is ephedrine, but it contains the same drug, but

what is on the label of that product as a matter of warning or recommended dosage is really not determined by the Food and Drug

Administration. That is determined by the manufacturer of the

product.

Mr. LEVITT. That is correct.

Senator DURBIN. OK.

Mr. LEVITT. That is because, as you pointed out in your opening

statement, when Congress passed the law there was a presumption

that these were natural ingredients with a history of safe use, and

therefore, that was an appropriate way for them to be marketed.

Senator DURBIN. But if you blindfolded a chemist and walked

him in and said, ‘‘I have got ephedra or ephedrine coming at you

in three different forms,’’ it is still that drug, whether it is from a

botanical source or from a prescription drug or from an over-thecounter, it is still that basic chemical compound coming into your

body?

Mr. LEVITT. There are clear similarities.

Senator DURBIN. Now, when it comes to the manufacturing practices of these drugs and over-the-counter products and supplements, I understand the Food and Drug Administration monitors

12

very carefully how drugs are manufactured in terms of foreign matter as Ms. Heinrich and others have said, and in terms of its purity. The same thing would be true for over-the-counter drugs, is

it not?

Mr. LEVITT. Yes.

Senator DURBIN. But when it comes to dietary supplements,

what standards, when it comes to manufacturing practices, would

the FDA impose on the supplement industry?

Mr. LEVITT. Well, the law does explicitly authorize FDA to issue

good manufacturing practice regulations. We did issue, some years

ago, what’s called an advance notice of proposed rule making. We

do have a proposed rule which we hope to get out very shortly that

would elicit public comment, but really take us a major step towards getting those kinds of regulations in place. Again, I think

there was a broad support for getting those kinds of regulations in

place. Everybody recognizes the need for them.

Senator DURBIN. I have been around Washington long enough to

know that things do take some time, but we are talking about a

1994 law, are we not?

Mr. LEVITT. That is correct.

Senator DURBIN. And we are talking about the fact as we sit here

today in 2002, we are talking about public hearings on good manufacturing practices for dietary supplements.

Mr. LEVITT. That is correct.

Senator DURBIN. They have not been established?

Mr. LEVITT. Yes, correct.

Senator DURBIN. The products that are currently on the market,

the dietary supplements, for example, that are currently on the

market are not being manufactured according to any standards

that have been established by the Federal Government or the Food

and Drug Administration?

Mr. LEVITT. That is right.

Senator DURBIN. It is up to—— Mr. LEVITT. That’s why we think it’s important to do it.

Senator DURBIN. I think it is too. That is why it is really up to

every individual manufacturer to call their own standards, call

their own shots in terms of what they put in that bottle and how

they label it.

Mr. LEVITT. At this point in time, that is correct.

Senator DURBIN. And, Ms. Heinrich, what have you found, as you

have looked into these products?

Ms. HEINRICH. Well, certainly the reports in the literature are

that there is contamination, that there is variability in terms of the

dose, that you can’t assume that what the label says is what you’ll

find in the product. And the other area that is of growing concern

is the fact that many supplements, the dietary supplements for

weight loss especially, have multiple ingredients, as I said, up to

22 ingredients, and they may not—you may not have the information about what dose is in the product.

Senator DURBIN. Mr. Levitt, I mentioned in the opening statement the action taken by Canada, which basically has recalled

these products, ephedrine products, particularly those combined

with a stimulant, and said that they are a danger, and they are

very explicit in terms of the danger that they see here, in terms

13

of heart attack, stroke, psychotic episodes, seizures. What kind of

notice does the FDA take of that action in Canada; what kind of

reaction has the FDA had to that Canadian decision?

Mr. LEVITT. I think there were two reflections upon that action.

No. 1 is that action closely resembles a proposed regulation that

FDA issued several years ago, and therefore is consistent with

some of the steps FDA historically has sought to take.

No. 2, as I understand the Canadian framework, they have a different legal framework, and that these products are generally not

lawfully available in the country as they are here. And so they’re

operating within a different framework, but actually looking to this

country for what actions have been taken in the past.

Senator DURBIN. Well, I do not quarrel with that. I understand

that our 1994 law is different from the Canadian law. But what I

am asking for is not from the legal interpretation, although I know

you come to this as a lawyer, but I am looking from the medical

and scientific side. If we have a neighbor to the north which is considered very similar to the United States in its culture and values,

which shares our pharmaceutical products on a regular basis because of the trust we have engendered between the two countries,

and they have taken a product which we have for sale in drug

stores and nutrition stores across America, and announced that it

is unsafe for Canadians, so unsafe that they recalled it from the

shelves, what I am really driving at is from the medical and scientific viewpoint, did that not raise a red flag at the FDA that perhaps we are not moving quickly enough or not taking this concern

seriously?

Mr. LEVITT. Well, let me read to you from the HHS press release

of June 14, which I think speaks directly to that point. It says very

clearly, and I quote from our deputy commissioner, ‘‘These products

are not for everyone.’’ ‘‘Consumers should read labels carefully to

ensure their proper use.’’ It goes on to state that consumers should

not use these products if they are under the age of 18 or if they

are pregnant or nursing women. It further states that adult consumers should consult health care providers prior to use of such

products if they have current or previous history of high blood pressure, heart or thyroid disease, a seizure disorder, depression, diabetes, difficulty urinating, prostate enlargement, glaucoma, or are

using any prescription drugs. It goes on to alert consumers that

this is a product we have concerns about, and that consumers

should be vigilant as they take these products for possible side effects, and that specifically, ‘‘Consumers should discontinue use if

any of the following symptoms are experienced: Rapid or irregular

heartbeat, chest pain, severe headache, shortness of breath, dizziness, loss of consciousness, sleeplessness or nausea.’’

So I think that we clearly have recognized some of the potential

concerns with this product, have tried to alert consumers to that,

and we reinforce that message whenever possible, and I thank you

for the opportunity to reinforce that today.

Senator DURBIN. Well, I am glad you did reinforce it. With all

due respect, that is a press release, is it not?

Mr. LEVITT. Yes.

Senator DURBIN. Yes. And I do not know how many people read

it when you issued it, but when I go into my corner drugstore in

14

Springfield and buy a dietary supplement with ephedra in there,

am I going to find that warning on the label?

Mr. LEVITT. You will find a number of warnings that are voluntarily put on by the manufacturers, and they tend to be of the first

kind of language I read on the kinds of consumers that should

avoid using the product or consult a physician before using the

product. But that is consistent with what you’ll find on a lot of

products.

Senator DURBIN. But it is a voluntary label.

Mr. LEVITT. That is correct.

Senator DURBIN. We have seen some disclosures already that do

not get even close to the warnings which you have just outlined,

which are lengthy. It sounds like the end of one of these ads on

television about the little purple pill. But what I am saying to you

is it is voluntary, and from a consumers’ viewpoint, unless you happen to be on the mailing list from the FDA and got a copy of that

press release, you may never see the warnings which you have laid

out here; is that not correct?

Mr. LEVITT. It is correct that the warnings are voluntary, and we

do try to get this message out as broadly as we can.

Senator DURBIN. Let me ask you about the dosage level if I can,

and we apparently have some difference of opinion between the

United States and Canada as to safe dosage, and I might go further to say that when you look at the actual products being sold,

it appears that some of the companies are paying little or no attention to either standard as announced. Is there a safe dosage standard for products containing ephedrine supplement products that

the FDA has announced?

Mr. LEVITT. Let me share with you the brief history on this subject. In the earlier part of the 1990’s, FDA had a Public Advisory

Committee meeting addressing the safety of ephedra products, and

the recommendation of the Advisory Committee was to see if FDA

could determine a safe dose or an acceptable dose. FDA went back

to the existing body of information that the agency had, which was

the Adverse Event Reports, and used those reports as best as we

could, consistent with what’s known in the literature and about the

product in general and proposed a dose level. A study was done following that by the General Accounting Office. I will let them speak

if I say anything incorrectly and correct. But their conclusion was

that those Adverse Event Reports, while important in signalling a

potential problem with this product, were not designed to establish

a dose level, and it was not appropriate to use them for that purpose. And so where we stand today is that we don’t have a good

scientific foundation—goes back to my opening comments—a strong

scientific foundation. We don’t have a strong scientific foundation

establishing what is the best dose to use.

Senator DURBIN. We certainly do not, and I think the conclusion

from your statement is the following: The Food and Drug Administration since 1994 has not established a standard for safe dosage

of this product.

Mr. LEVITT. That is correct.

Senator DURBIN. The Canadians have reached a conclusion that

resulted in their withdrawal of this product from sale in Canada,

and we have seen other actions taken by other organizations, but

15

our government has not taken an action to either withdraw the

product or even to establish a safe dosage. Is it not also true that

the American Medical Association, after this Canadian action,

wrote to the Food and Drug Administration and made a recommendation concerning ephedrine products?

Mr. LEVITT. They have written to us.

Senator DURBIN. Do you recall what they asked?

Mr. LEVITT. In an earlier letter I believe they recommended that

the products be removed from the market.

Senator DURBIN. Letter of January 28, 2002 to Dr. Bernard

Schwetz, and this is from Dr. Michael Maves of the American Medical Association, first sentence, ‘‘On behalf of the American Medical

Association, I am writing to reiterate our call for the Food and

Drug Administration to initiate proceedings to remove dietary supplements containing ephedrine alkaloids from the United States

market.’’ He goes on to spell out the reasoning based on Adverse

Event Reports, and they are concerned about the danger of this

product as against its value to the American consumer.

The point I am getting to, Mr. Levitt, is it appears that the evidence keeps piling on to the Department of HHS and FDA about

the danger of this product, and as you come today to testify, 8

years after the law has been passed and as this evidence accumulates, it appears that nothing has been done. The proposed rules

are good and we will talk about when they might come about but

from the consumers’ viewpoint, neither a required warning label,

an established dosage, or any consideration as to whether some of

these products should be removed from commerce, none of this has

been taken despite the clear danger that was perceived in Canada

when it made this decision.

Now, is this for lack of resources at the FDA? Is it because your

hands are tied by legislation, or is there some other element at

work here?

Mr. LEVITT. It is because the data are not—there’s not a consensus on the clarity of the data to the point that you describe. We

held a public meeting with government officials on the panel a couple summers ago—I guess it was 2 years ago by now—and the outcome—and we presented all the Adverse Event Reports; we

brought our consultants. Some of the people testifying today testified at that meeting. The report coming out of that meeting reinforced that the Adverse Event Reports generate a strong signal, but

we did not have the kind of stronger clinical data that they would

like to have seen. We took that to the NIH and they commenced

what they call—because we said if we need more research, then we

need it—and what they call an evidence-based review. That is what

was in the HHS press release of June 14.

Senator DURBIN. Which we are hoping some consumers saw. Let

me ask this——

Mr. LEVITT. We are hoping it will result in firm recommendations and identification of the research we need to get to the bottom of it.

Senator DURBIN. Well, I hope you get to the bottom of it soon too

because you have had over 1,000 Adverse Event Reports which led

the AMA to say take this product off the shelf. Mr. Mangano has

made it clear—and I will return to him and ask this question—the

16

Adverse Event reporting for supplements in this country is woefully inadequate because it is voluntary. 13,000 adverse events

were reported to the Poison Control Centers in the year 1999 for

dietary supplements, and only 460 or 480 were reported to the

FDA. So clearly, this system of reporting is not giving the information from consumers to the industry to the FDA for them to make

a decision. And when we hear Mr. Levitt and the FDA say, well,

we just do not have enough information from Adverse Event Reports, this is circular, and frankly, it is leading to some disastrous

results.

Mr. Mangano, you have talked about changing this Adverse

Event reporting system. Would you comment on that?

Mr. MANGANO. Sure. The system itself is inadequate as a system

to collect data. I’m talking about the computerized system that actually houses all of the events reports themselves. It was not a system that could either house all the information or be used fully in

terms of analyzing the necessary information. So that needs to be

changed. I know that FDA has put about $2.5 million into that

process itself, but there are a whole lot of other things that have

to go on at the same time. The voluntary system just is not going

to work for the kinds of products that can cause risk through

human consumption.

We need to have reporting by the manufacturers of what the ingredients are in their individual products. We need to have mandatory reporting by the manufacturers of adverse events for some

products, products like ephedrine, that could cause problems. Right

now it’s voluntary. We need to complete the good manufacturing

practice standards, etc.

They need to learn a little bit more from the Poison Control Centers about the kinds of information they’re getting from that

source. They need to do all the kinds of research that Dr. Levitt

has just talked about.

The resources haven’t been there in the past for them, but they

need to really try and ratchet up developing the clinical studies

that will help them when they do get a signal that there might be

something wrong with a product. They need to have the clinical research that’s available to them to tell them whether they need to

act on it immediately.

So those are just a few of the things that need to happen.

Senator DURBIN. Ms. Heinrich, the GAO and the Inspector General have both looked into this Adverse Event Report situation

here, and I would like to ask you what role do you believe that this

adverse event reporting should play in protecting consumers from

potentially harmful weight-loss supplements?

Ms. HEINRICH. I think we have to be very thoughtful about the

design of this Adverse Event Reporting System. The fact of the

matter is you have to have good and complete data going into the

system. Then you have to have people that are able to look at those

events and decipher patterns or early warning signals that there

may be a problem. And then you have to have the ability to go further where there is a problem and do thorough investigations and

be able to link the clinical outcomes to the ingestion of one of these

dietary supplements.

17

The problem is that it is voluntary. In this instance industry,

manufacturers are not required to report adverse events that they

know about, and so with dietary supplements, you don’t have complete information on which to determine these patterns.

More to the point, when FDA does see a pattern as they have

said that they see in ephedrine, for example, they really have a

higher threshold of evidence that they have to have in order to

prove harm and possible public health safety concerns.

Senator DURBIN. I guess, Mr. Levitt, that is a point I am going

to come to here, and maybe that is a question for the FDA. I know

there are many doctors who work the FDA, and I do not believe

you are a medical doctor?

Mr. LEVITT. That is correct.

Senator DURBIN. I am not either. But—and I do not play one on

TV, even on C–SPAN. But I would say to you that it would seem

that the first obligation of the Food and Drug Administration is to

protect American consumers. When in doubt, err on the side of protecting American consumers. We have a situation here where you

have said the FDA just cannot reach a conclusion on warning labels, on dosage and the like, because we just do not have enough

information. We do not have enough statistical data on Adverse

Event Reports. We know the system is stacked against you. The

law that was passed in 1994 makes those reports voluntary. The

industry is not rushing to your door to saying, ‘‘Oh, listen, there

are some more reports on bad outcomes with our product.’’ In fact,

they are holding back on that information. And so you do not have

the information to deal with. The Poison Control Centers are learning a lot more than the FDA. What is wrong with this picture? And

so you do not have the statistical information coming in to make

an ordinary decision about how to protect American consumers, but

you do know something. You know that the Canadians have come

to the conclusion already that this is unsafe to be sold in their

country. You know as well that 21 States or more have established

stricter standards than the Federal Government when it comes to

the sale of these products. You know as well that the American

Medical Association, which is not considered a fly-by-night operation, has notified the Food and Drug Administration that there is

a real danger in the sale of these products. You know that three

football players dropped dead after taking these supplements and

the NFL has banned it, as well as the International Olympic Committee and the NCAA.

When all of this accumulates, does not the Secretary of Health

and Human Services come to the conclusion that I should err on

the side of protecting Americans? These products are killing people

and hurting people, and we should err on the side of helping them,

rather than waiting for statistical evidence which by this law will

never appear.

Mr. LEVITT. Mr. Chairman, we agree with you that in this product area in general, this product in particular, is an area that we

need to be doing more.

Senator DURBIN. This has been 8 years.

Mr. LEVITT. We agree that our Adverse Event Reporting System

needs to be upgraded. We’re in the process of doing that. We thank

you for the funds to do that. I also want to reinforce a point made

18

by my colleagues. The Adverse Event Reporting System needs to be

an effective tool for an early warning of problems, but that early

warning system, once a problem or potential problem is identified,

needs to be complemented with a broader, stronger, scientific foundation of information. We will continue to search for ways to get

that information, and to meet our responsibilities under the law as

best as we can.

Senator DURBIN. I do not want to assign the blame to you personally, and I do not. I do not necessarily want to assign it to the

FDA because I respect this agency more than you can imagine. But

either the law is bad, the resources are not being given to you, or

there is no will to deal with a clear threat to the American consumers. It may be all three. I hope not. And I hope that we can

make some steps to resolve it.

Now, let me ask you about one particular bill before I draw this

panel to a conclusion. When we passed the Bioterrorism Bill, we

called for the registration of food manufacturers, distributors and

importers. So can I conclude from that that at least now the most

basic information about the identity of supplement manufacturers

will now be available to the Federal Government?

Mr. LEVITT. That is correct. Dietary supplement manufacturers

are clearly included under the law. In fact we had our first outreach meeting with industry in general on these provisions just

yesterday. A number of dietary supplement representatives were

there. And I think everybody accepts and recognizes that as a very

positive step.

Senator DURBIN. Now, let me also add, too, is it not a fact that

some businesses within the supplement industry have tried to create their own code of good conduct and manufacturing practices to

try to establish some standards that have not been imposed by the

government?

Mr. LEVITT. That is correct.

Senator DURBIN. But there are some companies that are not part

of that code.

Mr. LEVITT. That is correct also.

Senator DURBIN. Well, this raises another question as to whether

or not the industry itself perceives a problem. Can any of the witnesses at this table testify about the question of lawsuits and

claims against the supplement industry? Did that come up during

the course of the GAO investigation?

Ms. HEINRICH. We did indeed try to document the types of claims

that have been filed, and there are several. And certainly ephedra

is involved in several lawsuits. You’ve had claims brought by State

Attorneys General, and then you have also had liability claims

from individuals.

Senator DURBIN. Thank you.

If there is anything else that any of the panel members would

like to say at this point, I will give you this opportunity. If not,

thank you very much for your testimony. I appreciate it.

I think we will go ahead and bring on the second panel. We may

have to interrupt it if there is a vote. Let me invite Cynthia Culmo,

who is Chairperson for Drugs, Devices, and Cosmetics with the Association of Food and Drug officials in Austin, Texas; Dr. Steven

Heymsfield, Deputy Director at the Obesity Research Center, St.

19

1The prepared statement of Ms. Ruiz appears in the Appendix on page 118.

Luke’s-Roosevelt Hospital Center, Professor of Medicine, Columbia

University, College of Physicians and Surgeons in New York; Michael McGuffin, President of the American Herbal Products Association from Silver Spring, Maryland; and Karen Ruiz, a consumer

from San Clemente, California.

As you probably noted before, we do ask our witnesses to take

an oath, and if you will please stand.

Do you solemnly swear the testimony you are about to give is the

truth, the whole truth and nothing but the truth, so help you, God?

Ms. CULMO. I do.

Dr. HEYMSFIELD. I do.

Mr. MCGUFFIN. I do.

Ms. RUIZ. I do.

Senator DURBIN. Let the record indicate that all four of the witnesses answered in the affirmative, and we will start with testimony.

And let me begin with Mrs. Ruiz. Thank you for joining us from

California today. We have your statement for the record, and if you

would like to give us a summary of your experience for the record,

I would appreciate that.

TESTIMONY OF KAREN RUIZ,1 CONSUMER, SAN CLEMENTE,

CALIFORNIA

Ms. RUIZ. This is amazing, and I want to thank you for having

me here. Senator Durbin, I would like to thank you for taking the

time to hear my testimony, and it is my hope that by sharing with

you that others will be spared the serious and life-changing effects

of taking unregulated diet supplements, specifically containing

ephedra and guarana.

I would like to just read to you a journal entry I wrote. I grabbed

this at the last minute. But it’s impacted my life, it’s impacted it

a lot, and I wanted to read this to you. I wrote: ‘‘I’m 32-years-old

now and determined to journal a lot more consistently. Today I feel

good. About 4 months ago I had my third manic episode. It baffles

me how my mind can completely take me to non-reality and I am

completely helpless when it happens. It just happens. And when it

does, it seems so wonderful and perfect, and everything seems to

come together and make such perfect sense. But always only to me.

Once Donny, my husband, realized I was manic again, he took me

to the doctor. Three weeks of heavy sedation and lots of sleep

brought me down, but then comes the depression. And so horrible

is this hopelessness that I don’t know how I survived it again. But

today I feel good and I thank my God for restoring my mind to me

today. It is my biggest prayer these days that my medication will

work and keep me from getting sick again.’’

‘‘My story and how I first developed this illness with these

ephedra supplements will be in ‘Self Magazine’ next month.’’ This

was back in April 2000. ‘‘And I’m a little nervous about seeing it.

I hope it doesn’t make me sound crazy.’’

It was in February 1996 that I first took these supplements containing ephedra and guarana. The ephedra was listed as ‘‘ma

huang’’ on my bottle. That’s the Chinese herbal name, and I just

20

think that it’s important to note that many of the dietary supplements out there do say ma huang. They don’t say ephedra. But it’s

the same thing.

I had two small children and I was looking to lose post-pregnancy weight, also get a little extra energy. I was tired from getting up at night with the kids. I was drawn in by claims that it

was all natural, and that it was safe. I had attended a meeting and

asked questions about this product, and I was given brochures that

used words like ‘‘doctor recommended,’’ ‘‘scientific approach,’’ and ‘‘quality assurance.’’ I was very impressed with the entire presentation, and I found myself feeling very comfortable about taking

these products. And I was pretty cautious. I didn’t want to take

anything that wasn’t legal or drugs. I never had.

When I first started taking the products, I want to just tell you

I immediately felt the lift in my energy. They said I would and I

did. And for the first time in months, when my children took their

naps, I didn’t have to nap along with them. On day 3 after starting

the product I woke up early and actually went to the gym before

daybreak, and I came home and completely cleaned my house before the kids woke up.

My days were full and every minute was being used, and I felt

very productive. There seemed to be no limit to my energy, and by

day 4 I had come up with a new marketing plan for this company

and was seeking legal advice on how to patent it. I had a lot of

friends and a lot of moms who I knew needed this product. The energy was amazing.

But it was around day 5 that I began to feel something big was

happening to me, and I still made no connection to the product. I

was not getting as much sleep, and when I asked my direct distributor, and told him I was not getting as much sleep, his response was, ‘‘Isn’t that great. You are getting so much healthier,

you do not need as much sleep.’’ That was not a red flag to him,

it was not a warning, and if he was not concerned, I was not concerned.

I remember I was suddenly feeling very aware of a spiritual

realm, and at one point I felt that I was being watched, and I remember thinking my neighbor was demonically possessed. I was

flipping in and out of paranoia, but then followed by thoughts of

what I presumed were divine and coming from God. I somehow was

convinced that I was being chosen, initially to warn people that it

was the end of the world. I went to my bank account, pulled out

twenties and started handing them out to homeless people and saying, ‘‘We are almost there. We are going home.’’

Later, I thought I was being chosen to be God’s wife, and eventually I just felt so euphoric and so in tune with the cosmic around

us that I just thought I was God myself. It was an incredible way

to feel, and I want you to know that I think I understand why people do drugs now. I had never experienced anything like that, and

it does not surprise me to learn that teenagers and kids are using

these products to get high. It is called herbal ecstacy on the streets.

By day 5 and 6, my husband knew something was wrong, and

he took me to the hospital. They admitted me, and I was fortunate

to have a psychiatrist who had been an emergency room physician

prior to being here on this ward, and he took the supplements from

21

my husband. (My husband believed they were responsible.) The

psychiatrist immediately identified the ephedra, the ma huang.

There were some additional stimulants in the product, and he said,

‘‘She is on amphetamines. She is high.’’ I was there for 10 days, and after 10 days, a lot of medication,

my mind did start to slow down, but I had a very hard time believing the things I was seeing, and hearing, and feelings were not

real. I mean, I was seeing visions in the clouds. So, when you are

seeing them, the person next to you cannot tell you that they are

not there, because I was seeing them.

So I did eventually get well. It took 9 months, and following the

initial incident—we did report it to the people who had sold it to

me. Basically, they said, ‘‘Oh, gosh. We are really sorry. We have

never seen that before. Bye.’’ They never called or followed up or

tried to get any kind of reaction. We felt lucky that we did have

an attorney who knew me personally, knew that was very abnormal and had not happened to me before. He took our case on a contingency basis, and with lab tests, we realized that the products

had no quality assurance. I had additional sources of ephedra in

the product, in addition to the ma huang that was listed on the

label. There were multiple kinds.

There was also guarana in the product not listed on the label,

and I was taking it with another drink that was a guarana

caffeinated drink so—— Senator DURBIN. Guarana is basically a stimulant?

Ms. RUIZ. Yes. The guarana is the herbal equivalent to caffeine,

but there were no specifications of how much or anything like that.

My cautions label said, ‘‘Don’t take if you are a nursing or lactating

mother or you are having high blood pressure,’’ and that was about

it, nothing else.

The doctors concluded that I had one of two things happen. I

somehow had a predisposition toward mental illness which had

never shown up before, and the supplements triggered its appearance or the supplements actually altered my natural brain activity

and caused me to have symptoms similar to bipolar illness. Either

conclusion is scary.

I know for a fact I am not alone. I have been fortunate enough

to do some news clips and some media. It has been written up a

few times, and I am amazed how many people actually see the article, make the connection of what is happening in their life, and

they call me or it is the spouse of someone who calls me or it is

a mother, and their daughter has been in the psychiatric hospital

for 3 months, and she is just making the connection that she was

taking Metabolife for 3 months before that.

And they are calling me looking for hope. They want to know

what doctor I went to. They want to know how I got well, and they

are lost. I always do my best to tell them how I got to a place

where I could handle it and tell them to call the FDA.

So I would like to just conclude with my thoughts on what would

have helped. Even those extensive labeling conditions would not

have applied to me. I was completely healthy. I had no preexisting

conditions, and so those warning labels did not apply to me.

I have seen them now in grocery stores. I did not use to see them

so much, but now I can go to my coffee shop. They are all on the

22

1The prepared statement of Dr. Heymsfield with attachments appears in the Appendix on

page 123.

counters. ‘‘Here, take this. Drink it with your coffee,’’ you are out

the door. They are everywhere.

Before I came, I walked into a Wal-Mart and bought three herbal

products with no posted warnings anywhere. I would recommend

posted warnings be required, at the very least. I also would recommend that number, the FDA’s number, be put on all labels of

these supplements immediately. We tried to report it to the FDA.

We got lost in the phone loop, and I do not know if I am part of

those statistics.

I would just like to conclude with saying that in articles I read,

representatives for the industry repeated claim that cases like

mine cannot be scientifically proven, and yet it is the industry

which should have the requirement to prove that their products are

scientifically safe. I did not abuse this product. I did not take more

than was recommended. Until that can be done, and the medical

communities agree, and the manufacturers, they both agree on

some kind of safety standard, then I would like to see it pulled off

the market.

So please use your influence and power to make a difference.

Thank you.

Senator DURBIN. Thank you very much, Ms. Ruiz. Dr. Heymsfield, thank you for joining us.

Dr. HEYMSFIELD. Thank you very much.

Senator DURBIN. Your testimony will be part of the record, and

we invite you to summarize it at this point.

TESTIMONY OF STEVEN B. HEYMSFIELD, M.D.,1 DEPUTY DIRECTOR, NEW YORK OBESITY RESEARCH CENTER, ST.

LUKE’S-ROOSEVELT HOSPITAL CENTER, PROFESSOR OF

MEDICINE, COLUMBIA UNIVERSITY, COLLEGE OF PHYSICIAN’S AND SURGEONS

Dr. HEYMSFIELD. Thank you very much.

More than half of adult Americans suffer from overweight or obesity, and rates are skyrocketing in children and adolescents. Overweight and obesity are just spectrums of being overly fat.

Many of those who are overweight or obese suffer from related

illnesses such as diabetes and cardiovascular diseases. The obese

are discriminated against in all aspects of their lives—social, professional, and economic. Strong societal forces, along with the medical establishment, encourage overweight Americans to lose weight.

A large percentage of overweight and obese individuals are currently dieting for weight loss at any point in time, as you had mentioned earlier.

While advances are rapid, almost breathtaking, scientists still do

not have a complete fundamental understanding of why some people are prone to gain excess weight. Moreover, our nutritional medical treatments have limited effectiveness for the population as a

whole. This creates a highly volatile combination: Tremendous consumer need and demand for weight-loss treatments, and yet a general lack of very effective nutritional and medical therapies. That

is a very volatile combination.

23

The vulnerability of overweight and obese Americans to purchasing magic bullets or untested and unproven treatments has

long been recognized by the FDA. The past is littered with unsafe

weight-loss treatments ranging from nostrums in the 19th Century

to amphetamines and Fen-Phen in the 20th Century.

Given the millions of Americans seeking weight-loss treatments,

some of whom harbor silent and potentially lethal diseases, the

FDA has set in place a rigorous system for two types of drug approval—prescription and over-the-counter, as we have already

heard today. A critical issue is that drugs in either of these

categories must not only be effective, but also be very safe so that

benefits outweigh risks. Moreover, diet and exercise are always

considered safe and inexpensive alternatives to pharmacologic

treatments.

In 1994, as we know, a third category of weight-loss treatments

emerged with the passage of DSHEA. An important concept inherent in the use of dietary supplements for weight loss is that beneficial effects would tend to be small, that is, less than that of a potent drug, and that by virtue of their presence in foods or herbs ingested by millions of humans over many, many centuries, they are

inherently safe.

The very stringent safety and effectiveness standards set for

weight-loss drugs by the FDA should, in theory, therefore, not need

to apply to products marketed under DSHEA. Most overweight consumers view dietary supplements, as Ms. Ruiz told us, often consisting of herbs and other natural ingredients, as inherently safe.

As we will see shortly, this regulatory position opened the window for the marketing of ineffective and/or unsafe products to highly vulnerable populations. The available dietary supplements for

weight loss purportedly suppress appetite, decrease hunger, limit

nutrient absorption, alter the partitioning of fat and muscle or

speed up metabolism.

Claims are that chitosan reduces fat absorption and promotes

weight loss. Hydroxy citric acid, also known as garcina cambogia,

blocks fat storage. Ma huang or ephedra suppresses appetite while

speeding up metabolism, and chromium picolinate promotes muscle

over fat formation.

Whether or not these dietary supplements work as proposed, to

a large extent, remains uncertain. We lack adequate numbers or

rigorous, mechanistic studies, and the benchmark for effectiveness,

randomized, double-blind controlled trials.

To highlight the current concerns related to dietary supplements

for weight loss, we can look at two groups of compounds, one that

is inherently safe, but appears to be ineffective so far, and the

other that is modestly effective, but appears to be inherently unsafe.

Garcinia cambogia, also known as hydroxy citric acid or HCA, is

found widely in dietary supplements for weight loss and purportedly blocks the synthesis of body fat. However, our group, and no

other scientist so far, have shown in well-designed clinical trials

that HCA either promotes meaningful, long-term weight loss or reduces body fat beyond that of a placebo or dummy pill.

HCA has very minimal side effects, and the risk to consumers of

ingesting these products appears to be negligible. The real risk is

24

to bypass a medical evaluation that might detect an underlying serious, and even life-threatening, medical condition.

The second example is based on the family of compounds that we

have been discussing today that are extracted from plants referred

to as ma huang or ephedra. Dietary supplements with ephedra are

widely used by consumers for weight loss and to enhance athletic

performance.

Ephedra alkaloids include ephedrine, the main ingredient in

small amounts of pseudoephedrine, phenylpropanolamine, and

other related molecules. Phenylpropanolamine or PPA was widely

used in over-the-counter weight-loss products until recently when

a commission study supported a significant link between hemorrhagic strokes and PPA.

As shown in the figure, which you can see up there, ephedrine

and PPA bear strong structural similarities to amphetamines. Amphetamines were marketed for weight control beginning in the

1950’s, but were addicting, had other serious medical side effects

and were ultimately restricted by the FDA for weight-loss treatment. I should add, in the 1950’s, I was told that there were very

clean homes in the United States because amphetamines were

strong stimulants, and we have heard from Ms. Ruiz, a very similar story about ephedra.

Most of the evidence we have so far is that ephedra alkaloids, notably ephedrine, act in the body in a manner nearly identical to

that of the synthetic drug ephedrine. Dietary supplements with

ephedra are usually sold in combination with an herbal source of

caffeine. Caffeine, also a stimulant, amplifies the actions of ephedrine in the body.

The ephedra alkaloids and amphetamines are similar to the natural ‘‘fight and flight’’ hormone adrenaline. Like adrenalin, ephedrine speeds the heartbeat, increases blood pressure and stimulates

respiration. These agents, their actions well understood at the molecular level, are termed sympathomimetics, and their actions center both in the brain and peripheral tissues.

Most of the high-quality research in this area was carried out

using synthetic sources of ephedrine and caffeine in Europe, where

the combination is usually used under medical supervision. Studies

of dietary supplements with ma huang or ephedra are limited to

short-term evaluations, usually less than 6 months. These studies,

including some that I have participated in, reveal to us that

ephedra with caffeine or dietary supplement counterparts produced

a modest weight loss above that of placebo by roughly 2 pounds per

month. These trials also reveal the expected stimulant effects of

ephedra, palpitations, jitteriness and blood pressure elevations, to

name a few. In our own study at the New York Obesity Research

Center, an inordinate number of subjects dropped out of the protocol due to these stimulant side effects.

Although no heart attacks or strokes were reported in any of the

previous controlled trials, we need to recognize that subjects are

carefully screened. Those very individuals who harbor serious illnesses are usually eliminated from the study beforehand so as not

to place them at risk. The subjects in these studies, thus, do not

represent the consumer population. They are healthier.

25

1The questions and answers included in the prepared statement of Mr. McGuffin from AHPA

appears in the Appendix on page 139.

Also, rare side effects would likely not be observed in the clinical

trials that collectively to date have studied fewer than a thousand

subjects.

While clinical trials confirmed the stimulant effects of ephedrinecaffeine combinations, the real safety concern comes from the untoward effects reported by individual consumers, like Ms. Ruiz, or

their families to the FDA and from cases reported in the medical

literature. While causality is hard to establish in many of these

cases, we have strong evidence of an association between ephedra

use for weight loss or physical activity enhancement and strokes,

heart attacks and death.

Most of the individuals in these reported and analyzed cases

were not taking excessive or inordinate amounts of product. These

injuries are a predictable outcome of the known physiological actions of sympathomimetic agents such as ephedra alkaloids. These

are not weakly effective agents to which humans have been exposed for thousands of years in the food supply.

As DSHEA now exists, the vulnerable, overweight and obese

American public is exposed to an unfiltered and seemingly endless

source of dietary supplements of questionable safety and effectiveness.

I implore you and other Federal officials to appropriately and

ethically tighten this law.

Senator DURBIN. Thank you, Dr. Heymsfield.

As I mentioned at the outset of this hearing, there are a series

of votes that are now underway, and I have a few minutes to get

to the floor for the first of four. It could take 45 minutes before all

of those votes are completed. I assure you I will return just as

quickly as I can, but the hearing will stand in recess until the call

of the Chair.

[Recess.]

Senator DURBIN. My apologies to everyone for the lengthy recess,

but we had four votes, and on the Senate floor that can take some

time.

I believe that the next witness is Mr. McGuffin. Please proceed.

TESTIMONY OF MICHAEL McGUFFIN,1 PRESIDENT, AMERICAN

HERBAL PRODUCTS ASSOCIATION (AHPA), SILVER SPRING,

MARYLAND

Mr. MCGUFFIN. Thank you. Good, I guess it is afternoon now,

and thank you for inviting me to testify here today. My name is

Michael McGuffin, and I am President of the American Herbal

Products Association or AHPA.

Prior to this hearing, this Subcommittee asked AHPA to provide

responses to eight questions related to dietary supplements, and I

do ask that AHPA’s written responses be entered into the record.

Senator DURBIN. Without objection.

Mr. MCGRUFFIN. Six of the questions were directed to industry

practices and self-regulation. AHPA has been actively involved in

such efforts, and I want to describe two of them.

26

Many of our earliest self-regulatory efforts relate to herbs that

must be used with caution. AHPA established several trade recommendations, and those also are in my written testimony. One

example of these self-regulations is AHPA’s policy on ephedra.

In 1994, AHPA established a label policy that ephedra products

are not for use by children and that provides cautions for certain

populations with preexisting conditions such as high blood pressure

or diabetes. We revised this policy in 1995 to recommend dosage

limits.

AHPA testified before FDA’s Food Advisory Committee in both

1995 and 1996 and told them of our policies and urged them to recommend that FDA adopt them. In the meantime, the AHPA labeling has been adopted in several States.

In 1997, FDA proposed ephedra labeling and dosage limits, a

proposal that was controversial and has, for the most part, been

withdrawn. In May 1999, AHPA and other trade associations again

recommended that AHPA’s labeling and dosage guidance be adopted by FDA. This was repeated in October 2000 in the form of a citizen petition. There has been no action on the citizen petition, but

the Department of Health and Human Services issued a statement

last month regarding ephedra, and Mr. Levitt referred to that. The

language that Mr. Levitt read very much models the industry labeling language as important information for consumers.

I want to give another example of AHPA’s self-regulation that occurred in 1992, when we published a document called ‘‘Herbs of

Commerce’’ to establish a single standardized common name for

each of nearly 600 herbs. This was done to address potential consumer confusion because of the many different ways herbs are

named.

In 1997, the Food and Drug Administration incorporated Herbs

of Commerce into the Code of Federal Regulations so that the

names established by AHPA now have the force of law. FDA’s

adoption of AHPA’s Herbs of Commerce is an example of how government and consumers can benefit from industry’s self-regulatory

activities. The handling of the ephedra issue shows what can happen when positions become entrenched.

While there have been differences of opinion over the label language, these have been minor, and the principal controversies have

been over dosage levels. Stepping back from the fray, I believe consumers would have been better served if FDA had promptly sought

labeling while addressing dosage issues at a later date.

I want to address the common misperception that dietary supplements are unregulated. In fact the law requires dietary supplements to meet label claims, and these laws empower FDA to take

enforcement action if a product fails to do so.

The law requires all dietary supplement labeling and advertising

to be truthful and not misleading, and these laws provide FDA and

the Federal Trade Commission with authority to enforce them.

The law places the responsibility for product safety squarely on

the manufacturer, and it is a crime to introduce an adulterated

product into the market.

AHPA believes that there is not enough FDA enforcement of the

law and that the Agency’s priorities are sometimes ill advised.

When FDA does send warning letters, they are seldom followed up

27

1The prepared statement of Ms. Culmo with attachments appears in the Appendix on page

160.

with more aggressive enforcement when companies are not responsive. We have joined with other trade groups to successfully recommend an increase in FDA dietary supplement enforcement funding. I must say it is difficult for trade groups to urge members’ compliance, when those members must confront unfair and unlawful competition on a day-to-day basis and not see FDA enforcing

the law. It is time to see FDA take full responsibility for the implementation and enforcement of a law that is almost a decade old.

Let me close by saying that we are an industry that is committed

to providing benefits to American consumers through our products,

including products for those who are overweight at a time that the

medical community has declared an epidemic of overweight in our

country. ‘‘When Diets Turn Deadly’’ is a sensational title for today’s

hearing, and perhaps it evolves from recent history, not just in our

industry, but also with drugs and problems in other countries.

The title is not, however, substantiated by any balanced, unbiased and thorough review of the body of science and experience for

any of the dietary supplement agreements that are broadly available in the market, and that are manufactured, labeled and consumed according to established industry policies.

Thank you very much.

Senator DURBIN. Thank you, Mr. McGuffin. Ms. Culmo.

TESTIMONY OF CYNTHIA T. CULMO, R.Ph.,1 CHAIRPERSON,

DRUGS, DEVICES, AND COSMETICS COMMITTEE, ASSOCIATION OF FOOD AND DRUG OFFICIALS, AUSTIN, TEXAS

Ms. CULMO. Good afternoon. I am Cynthia Culmo. I am here as

the chairperson for the Drugs, Devices and Cosmetics Committee

with the Association of Food and Drug Officials. The points that I

am making, as well as those in my written comments, are a compilation of comments that were submitted from multiple-State

AFDO members. For the complete version of our position, please

refer to those written comments.

We thank you, Mr. Chairman, for the opportunity to participate

in this important and critical discussion. It is extremely difficult to

roll in 8 years of experience, knowledge and information into 5

minutes, but for time’s sake, I will try and summarize most of our

concerning points.

There have been more serious adverse-event reports for dietary

supplements containing ephedrine alkaloids than for any other

type of dietary supplement or over-the-counter phenylpropanolamine drug products, which were recently withdrawn from all U.S.

markets due to the increased risk of hemorrhagic stroke in young

women.

These serious adverse-event reports included psychoses, seizures,

strokes, heart attacks, and death. These are known and expected

consequences on the use of ephedrine. Pharmacologically, as what

has been discussed, in the body there is no difference between natural and synthetic ephedrine. They act the same in the body.

By regulation, drug products containing ephedrine cannot be

combined with other stimulants. This is based upon the potential

28

1The chart appears in the Appendix on page 173.

for abuse and safety concerns. However, currently marketed dietary supplements for weight loss do contain ephedrine plus other

stimulants.

Almost all of the products on the market are multi-ingredient

products. They are ephedrine combined with other stimulants,

diuretics, laxatives and other active ingredients. This explains the

high number of adverse-event reports for these products.

You can see how well it is demonstrated—I believe the chart is

up 1—in the American Association of Poison Control Center data,

as shown on this table, how the incidence of adverse-event reports

has increased since the Dietary Supplement Health and Education

Act.

These multi ingredients can interact with each other, with other

products, being drugs and/or foods, and there are drug disease

interactions. Studies are beginning to identify these complex interactions, which have definite effects on the safety of the products.

These products are also marketed for a disease—obesity. Although the industry routinely claims that their products are not

drugs, they are posed to the consumer as drug products by their

claims, the manner that they are advertised, as many of them are

advertised in the Physician’s Desk Reference for Nonprescription

Drugs and Dietary Supplements now, as well as the way that the

information is shared with health professionals and other consumer

information, all of which results in misled consumers and medical

professionals.

The studies that industry uses to support safety comes from foreign data on prescription drugs, using pharmaceutical ephedrine.

None of these studies can be used to support the safety of dietary

supplements. These products are not the same. There are numerous methodology problems with the relative few studies in the

United States, which include, one, being too small; they are not

using the marketed products. For instance, the industry-touted

Boozer study, the 6-month study, it did not use Metabolife 356 as

that company elaborates. So the results of these studies cannot be

applied to the general population for weight loss.

DSHEA shifted the requirements proving a product is unsafe to

the government. Many States have picked up this tremendous burden because of the apparent inability of the Federal Government

to effectively address safety issues associated with these products.

The enforcement actions by the States are labor- and time-intensive. They are done with great difficulty and fierce battles with the

industry and their political supporters. Politics and bureaucratic

entanglements have prevented FDA and FTC from accomplishing

their responsibilities.

Under DSHEA, safety is addressed after the harm has already

occurred. The standards and the criteria of safety have never been

defined by FDA or the courts. A major question that is yet to be

answered is what is questionable or unreasonable risk that causes

a product to be adulterated?

The most egregious safety problems with the dietary supplement

for weight loss are the products containing ephedrine. The situation is not a scientific issue any longer. It is a political issue run

29

by a political agenda. There are ongoing conflicts between good

public health and the industry’s economic needs, with politics frequently serving as the referee.

Consumers are being misled, and they are not getting the full

story about the risk associated with these products. They cannot

make an informed decision about appropriate use. So labeling and

warnings cannot solve safety issues. The warnings and the labels

will not help when you do not know you have a condition that

places you at increased risk.

This has been our most concerning point, and please refer to our

written comments for a complete summary. But as you can see, the

States have indicated that there are numerous problems associated

with dietary supplements for weight loss, and they have recommended a number of solutions:

Except for traditional nutrients, such as vitamins, minerals, etc.,

prohibit or limit botanicals and other natural products to a single

ingredient. I am sure that has made several in the room gasp, but

this is exactly what Health Canada has done with ephedra. If you

are going to retain a combination of products as a dietary supplement, then they should be required to have premarket review for

safety;

Require manufacturers and distributors to register with the FDA

and to list their products. This will enable FDA to develop appropriate product databases, to evaluate the product adverse-event reports, and the interactions;

Institute mandatory adverse-event reporting, which is analogous

to what is required for drugs, biologics, and medical devices;

Implement a single adverse-event reporting system within FDA;

Adverse-event report evaluations and risk management is best

directed by the regulatory agencies. Therefore, communications and

interactions should be enhanced between State and Federal agencies and the general public;

Define the criteria for the DSHEA standard of significant or unreasonable risk. What is the standard to prove a product is unsafe?

From a science perspective, if what is currently known about

ephedra supplements cannot meet the standard, nothing else ever

will;

Create a specific center within FDA for traditional medicines and

dietary supplements for the regulatory oversight;

And last, and certainly not least, appropriate funding is necessary for all of the above.

In conclusion, we appreciate this opportunity to provide you with

our comments. AFDO believes that products current marketed as

dietary supplements for weight-loss purposes are either not safe or

are of unknown safety, and the public health is not being adequately protected. Thank you very much.

Senator DURBIN. Thank you very much, Ms. Culmo.

Mrs. Ruiz, have you encountered individuals who continued to

use these weight-loss supplements even though they told you they

had had some bad side effects?

Ms. RUIZ. Actually, yes, and the reason for that is because they

do not attribute the supplements to the problem.

I have been in contact with one family and he was training as

an athlete. He was taking a product he bought at a bicycle shop.

30

And when he had heart palpitations, (he was running), they took

him to the hospital. They told him he was low on electrolytes, so

he went home and took more of the product to help with his electrolytes. He then had a full-blown psychosis after that.

So usually they do, but because they do not know it is causing

the problem.

Senator DURBIN. Can you tell me how many individuals you estimate you have spoken to who have had negative experiences with

ephedra-based dietary supplements?

Ms. RUIZ. Over the last 6 years, I have probably spoken with 10

very serious cases, and then quite a few individuals on a daily

basis. I spoke at one recovery group with about 100 individuals in

the room, and they were recovering from all kinds of things. I was

talking about bipolar specifically, but I had talked about what triggered the event. After that meeting, I had six or seven different individuals come up to me who were dealing with depression, dealing

with psychosis issues, and they were like, ‘‘I was taking this product and this product. And does this have ephedra in it?’’

And all of them I was like, ‘‘Yep, yep, yep.’’ I was amazed.

And then when I go to talk with my psychiatrist. (I have to see

him for regular check-ups.) He explains how now he always asks

more questions of new patients. Instead of just, ‘‘Are you on any

prescriptions or illegal substances,’’ now he goes beyond, and he

says, ‘‘Are you taking any supplements, any vitamins? Have you

been doing anything new lately?’’ And what he usually uncovers is

that there is this supplement they have started. They think they

are taking a vitamin but he has them bring them in. His cupboards

are packed with Xenadrine and Metabolife, and Pure Ephedrene

from GNC. And he is amazed how many people come in to see him.

So it is a daily thing for me to run into people like this.

Senator DURBIN. Dr. Heymsfield, have you had any patients in

your practice who have had problems with dietary supplements?

Dr. HEYMSFIELD. Well, I have, particularly in the studies that we

have done. When people go through the protocols, we have found

that a number of them get side effects—jitteriness, headaches, palpitations, elevations in blood pressure. And when we take them off

the study and break the code, we find that invariably they are on

the active treatment which are ephedra alkaloids.

Senator DURBIN. We talked a little bit, Ms. Culmo spoke a little

bit about combinations, and it appears that, unlike many products,

some of these dietary supplements and herbal products have a

range of different drugs in botanical form that are combined into

these supplements. What kind of challenge does this create?

Dr. HEYMSFIELD. Well, it creates a number of challenges. First,

those combinations usually amplify one another, so the effects can

be fairly potent. Also, in the case of caffeine, many people continue

to ingest caffeine in their daily lives out of colas, coffee, teas, and

so on. So they can get a very high dose of caffeine. That amplifies

the actions of ephedra alkaloids.

But the real challenge is we do not know how to assess the safety

and efficacy of these combinations because they are so variable.

One product might have a lot of one component and less of another,

so it is virtually impossible to make global statements about the efVerDate 11-MAY-2000 12:52 Jan 16, 2003 Jkt 000000 PO 00000 Frm 00034 Fmt 6633 Sfmt 6633 81314.TXT SAFFAIRS PsN: SAFFAIRS
31

ficacy and safety of products as a whole because they are so variable in these combinations.

Senator DURBIN. As Ms. Culmo said, whether it is synthetic or

botanical, it is still the drug that is being ingested into your system

with the drug’s impact.

Dr. HEYMSFIELD. Your body does not really know the source of

where that molecule came from. It sees ephedrine, as either a botanical or a synthetic component, is identical.

Senator DURBIN. I guess it bears repeating that under the law

we treat that entirely differently.

Dr. HEYMSFIELD. That is right.

Senator DURBIN. Whether you are dealing with a synthetic that

is being prescribed or over-the-counter, it is subject to strict regulation in terms of how it is manufactured, how it is marketed, the

quality of the drug, the dosage, the warnings, they are extensive.

On the supplement side, there is very little, if any, regulation, in

terms of those elements as I see them.

Now I would like to address the issue that Mr. McGuffin has

raised. He has taken issue with my reference to the fact that the

title of this hearing is ‘‘When Diets Turn Deadly.’’ That was based

on the Canadian situation where, in fact, they warned the people

of Canada of possible fatal effects of these ephedrine dietary supplements, and so the title was chosen based on the experience of

Canada.

Do you have any knowledge or any impression of this Canadian

decision relative to these products, Dr. Heymsfield?

Dr. HEYMSFIELD. Do I have an opinion?

Senator DURBIN. Any knowledge or impression of this Canadian

decision.

Dr. HEYMSFIELD. No, I do not, but it seems very well-founded, in

my personal opinion, and it would seem, based on the same literature that I have reviewed, in the United States there have been

a number of studies in very prominent journals showing the very

high risk of ephedra alkaloids and ephedrine.

Senator DURBIN. The Canadians came to the conclusion that

these products pose a significant threat of danger to the public

health of their citizens. Do you believe that these products for sale

in the United States pose a significant threat of danger to public

health?

Dr. HEYMSFIELD. I do, and I will tell you why I feel that way,

and that is because many of the people who take these products

are just like Mrs. Ruiz, who do not really read the labels carefully,

who harbor silent diseases, and that can be triggered by ingestion

of these products. So I think it poses a very significant risk to people.

Senator DURBIN. Before asking Mr. McGuffin, I am going to ask

the same question of Ms. Culmo. Do you feel, as a registered pharmacist, that these ephedra-based dietary supplements pose a significant threat of danger to the health of American citizens?

Ms. CULMO. Yes, definitely, and I believe the association would

support the position as well. We are of the opinion that the evidence is there. The data and the information is available, and it

is a conclusion that has been made by our association several

times.

32

We would also venture to say that your title, ‘‘When Diets Turn

Deadly,’’ is appropriate, as I am sure that the families of the 100-

plus people that allegedly died due to the association of these products supports the position that Canada took as well.

Senator DURBIN. Mr. McGuffin, I am not going to back off the

title of this hearing. I think, based on what you have just heard

from witnesses sitting on either side of you, and based on the decision of Canada, based on the letter you sent to the American Medical Association and the Food and Drug Administration, this is not

a casual or minor problem. It is life-threatening in many instances.

Mrs. Ruiz was lucky enough to survive the situation. Thank

goodness you are here today, and raising your family, and doing

well. Hers was a terrible episode, but she survived it.

You have talked to me about industry standards. These are voluntary standards, are they not, within your industry?

Mr. MCGUFFIN. They are today. We have asked that they become

the law.

Senator DURBIN. And those companies which market these products and do not belong to your association or do not subscribe to

these standards may ignore completely the dosage requirements,

the warning labels, the marketing, trying to keep these out of the

hands of children; is that not true?

Mr. MCGUFFIN. It is true. We believe we have had an influence

beyond our membership, but you know we have seen examples here

today of products that would not conform with the labeling recommendations of our trade.

Senator DURBIN. Well, it strikes me that we are in a situation

which is very strange, where your industry is coming forward and

saying to the government, ‘‘Regulate us more. We want more regulation.’’

Mr. MCGUFFIN. Enforce these regulations.

Senator DURBIN. I think that is certainly overdue—8 years overdue. But before we reach that question of how we properly regulate

these products so they are available, we have to ask, and answer,

the threshold question, are they safe, and if they are not safe, there

is no amount of regulation that could really cure the problem.

I guess that is a question I would ask, let us start with Dr.

Heymsfield. In terms of dosage, there seems to be a wide variance

of opinion here. The Canadians limit it to 32 milligrams a day. We

hear 100 milligrams a day from many people in the dietary supplement industry.

You have done some studies on this subject. What can you tell

me about dosage levels?

Dr. HEYMSFIELD. Well, the dosage levels that we used in our

studies were those that are commonly used in these products as a

whole, and certainly at those levels I would not say that we could

assert these products are safe. The question of whether or not they

might be safer at lower doses would have to be studied, and I have

questions about that for the following reason, and that is if you

lower the dose far enough, then you reduce the efficacy, the weightloss efficacy, to the point where it would hardly be worth taking

it. So I have questions about whether or not a dose reduction would

totally solve the problem.

33

1The information submitted by Mr. McGuffin appear in the Appendix on pages 146 and 157

respectively.

Senator DURBIN. So, if I were asking you to establish, based on

a reasonable degree of medical certainty, as they say, a safe dosing

regimen for a dietary supplement that still would provide the benefit of suppressed appetite, increased energy, are you saying that

you would have a tough time finding that number?

Dr. HEYMSFIELD. A very hard time finding that number because

when you got down to the levels I am hearing, the numbers I am

hearing, you would get virtually negligible weight loss. The weight

loss effects of ephedra alkaloids are already only two pounds a

month at the current dosage, which I think is unsafe. If you, say,

cut the dose in half or a third, you would almost wonder why you

would want to take the drug, which is what I will call it.

Senator DURBIN. This is obviously a question which Secretary

Thompson and the FDA has to resolve, whether on a public benefit

basis, the risk that you are encountering is worth the benefit. If

you can lose a pound a month or two pounds a month—is that

based on some study, incidently, that two pounds a month that you

have come with?

Dr. HEYMSFIELD. Well, there are growing numbers of collective

analyses called, meta-alyses, that are looking at the efficacy of

ephedra products, and the trend that I am seeing, including the

studies we have done at our center, are in the range of about two

pounds a month, and that varies a little. If you add the caffeine,

you get a bit more.

Senator DURBIN. Of course, according to the Canadian standard,

adding a stimulant or an analgesic, I think there has been some

evidence that adding aspirin or some other form of analgesic could

also create some complications with ephedra.

Dr. HEYMSFIELD. That is correct.

Senator DURBIN. Mr. McGuffin, you said that what you are looking for is a balanced, unbiased, and thorough review. Do you feel

that Canada made a balanced, unbiased, and thorough review of

dietary supplements that contain ephedrine?

Mr. MCGUFFIN. No, I do not, because my understanding is that

the Canadian rule was based on the FDA proposal, which was

based on Adverse Event Reports, and as the GAO has told us, they

do not believe that that is a good way to get to a dosage recommendation.

I am concerned. If I can, I would like to repeat something that

Mr. Levitt said earlier. He said that there is not a consensus on

the meaning of the adverse event data that is as clear as you have

described, sir; that it is not a black-and-white that we know that

there is—that these adverse events point out a danger, and I think

that it is important to remember that, and I am concerned that

some of the information is not included.

If I may, I would like to ask that two other documents be entered

into the record.1

Senator DURBIN. Without objection, certainly, it will be.

Mr. MCGUFFIN. There is a report called the ‘‘Safety Assessment

and Determination of a Tolerable Upper Limit for Ephedra’’ that

was prepared for the Council for Responsible Nutrition by Cantox

34

Health Sciences International and published in December 2000,

that came to a conclusion that a dosage of 25 milligrams per serving and 90 milligrams per day is safe when used in accordance

with standard industry labeling.

And there is a compilation of documents, comments of the expert

panel of the Ephedra Education Council on the Safety of Dietary

Supplements Containing Ephedrine Alkaloids, and it goes on for

another two lines. This was presented in April 2000 at the hearing

at the Office of Women’s Health.

I think it is that document or these documents that Mr. Levitt

was referring to, when we do not have a clear consensus. I appreciate greatly what these two scientists to either side of me are saying, and I do not believe any of us say that their points of view are

crazy or unfounded, but there is not a consensus. There are other

scientists who look at the same data and come to remarkably different conclusions by a very sophisticated scientific process, and

that needs to be considered.

Senator DURBIN. I will readily concede that there are areas of

science that are not precise. Certainly, political science is not precise. [Laughter.]

Mr. MCGUFFIN. Did you win all four votes? [Laughter.]

Senator DURBIN. But I can tell you this, I have spent a career

on this Hill listening to the scientific analyses of the tobacco companies. They always found a doctor, they always found a scientist

who could just prove to you that it could not possibly cause heart

disease, and cancer, and stroke and all of the rest.

And so I think what we have to do is ask what is a reasonable

scientific basis acknowledged by most, if not all, to base our conclusions.

I am troubled by the adverse event reporting that we heard of

earlier. To think how few, some estimate that only 1 percent of the

adverse events relating to dietary supplements ever reach the FDA,

and you heard the examples of the Poison Control Centers. Ms.

Culmo made that point as well. In 1 year they had 13,000 reported

events, and in that same year, fewer than 500 were reported to the

FDA.

That suggests to me, Mr. McGuffin, that you cannot really get

into the circular argument of the FDA that we would really like to

establish standards, but we need more adverse events reported to

do that. We do not have enough adverse events reported, and

therefore there will be no standards. Meanwhile, we seem to be, as

we stand here, watching group after group, State after State, organization after organization, and now countries saying the United

States is completely out of control here.

Mr. MCGUFFIN. Again, we have assisted many of those States in

adopting our policy. You pointed out 21 States. I was not aware of

that many, but we worked hard in several States to assist a process that would put our recommended labeling and dosage limit in

place and make it the law in those States. We are very supportive

of that.

Senator DURBIN. Was that part of your effort recently in Texas?

Mr. MCGUFFIN. We were involved in the communication with

Texas. We were concerned, at least an initial stage, on the inclusion of the 800 number because we think that system needs to be

35

patched up some. There are problems with the system, but we were

involved in that, and their warning label is very similar to the one

that we have been using for some years.

Senator DURBIN. You have all been very patient, but I want to

conclude the hearing, if I can, by asking an open-ended question.

It strikes me that we have two extremes here in terms of Federal

regulation. We have the regulation of drugs, which clearly involves

extensive testing and determination of safety and efficacy before it

can ever be sold in the United States. Then it is sold only with a

doctor’s supervision, by his prescription, her prescription, and of

course dosage and everything is being carefully monitored.

Circulars are sent to the doctors, to the pharmacy with all sorts

of information. Ms. Culmo, I bet you are called on from time-totime by patients who say, ‘‘Look at all of these medicines I am taking. Do they work together?’’ That is part of the people in pharmacology.

So we have a very thorough system of regulation, approval and

monitoring when it comes to drugs.

Then, when we get into the supplements and food area, it is totally the opposite, where you have a situation where the company

that makes the product decides what to put in it, the manufacturing practices to follow, in terms of making certain that it is unadulterated and is what it says on the label, the representations

on the label have to stand some tests, at least by the Federal Trade

Commission, maybe by the FDA. Ultimately, the whole question of

dosage and warning labels is still voluntary. The adverse event reporting, still completely voluntary on the part of the manufacturer.

So we have this wide chasm between these two approaches.

It strikes me that most people would concede that when it comes

to basic things like Vitamin C, and folic acid, that this supplement

in food approach is not to be quarreled with. I mean, we are talking about something that is fundamentally safe. You would have to

have hyper dosages to have very bad results. But now we have got

a middle category. We have a middle category of supplements that

are combinations of naturally occurring chemicals that are lifethreatening, in some instances, and certainly can create terrible

medical situations. I think Congress has defined the extremes, and

now has to come to the center.

I would like to ask you, Dr. Heymsfield, do we need to come up

with a new regimen of regulation for supplements, let us start with

dietary supplements, that perhaps does not go as far as drugs, but

takes us forward in terms of protecting American consumers?

Dr. HEYMSFIELD. Well, for one thing, we might consider changing

the name. Dietary supplement certainly gives the impression that

it is something normally in the diet or that it is supplementing

something normally in the diet. If products are specifically, say, for

body building, and they are anabolic steroid derivatives or if they

are for weight loss and they are ephedra alkaloids, we might want

to name them a little more specifically so consumers really understand what they are getting.

I also feel strongly that these regulations should be tightened

and that we should have much clearer guidelines for safety and efficacy of these products, and we should seek experts out like NaVerDate 11-MAY-2000 12:52 Jan 16, 2003 Jkt 000000 PO 00000 Frm 00039 Fmt 6633 Sfmt 6633 81314.TXT SAFFAIRS PsN: SAFFAIRS
36

tional Academy of Sciences and other esteemed bodies that can

help us with these.

Senator DURBIN. Ms. Culmo, what is your feeling about establishing some new category of regulation?

Ms. CULMO. Well, I believe that was part of our position through

our comments. I think it is also evidence from what other countries

do. The industry here is pretty quick to point out that these are

dietary supplements that have been used for thousands of years in

other countries, are currently used in other countries, when the

truth of the matter is they are actually addressed more commonly

as prescription drugs or prescription products in these countries,

and the traditional use is very different from what the commercialized use is right now.

So, definitely, it needs to be changed.

Senator DURBIN. Mr. McGuffin, what is your reaction?

Mr. MCGUFFIN. I would be very troubled by the idea of creating

a new regulatory category as much as anything because, as you

have pointed out, it is 8 years in, and we have not figured out how

to properly implement this one.

You have heard my testimony. What we believe needs to occur

is that the current law needs to be enforced. There may be some

refinements that would be appropriate for discussion. But the idea

of just wholesale starting a new category, just off the top of my

head here, sir, with no consultation with any of my Members, concerns me.

Senator DURBIN. I would say to you that you can argue that if

the current law were properly funded and enforced, we might not

be facing the problems we are today. The fact is that the government has not met its obligation and, as Ms. Culmo has suggested,

there has been extraordinary political involvement in terms of decisionmaking when it comes to dietary supplements. That is a fact

of political life.

I have been around here 20 years. The reaction to this hearing

on Capitol Hill, and off Capitol Hill, has been stronger than virtually any issue I have raised, including my hearings on tobacco.

So I know that there are a lot of strongly held views by consumers,

as well as the representatives of the industry in this town.

But I honestly believe that we have to come up with a better answer. I do not think what we have today is adequate. The first

thing that we have to do is establish whether these products are

safe, and if they are not safe, then, frankly, that is the end of the

story, as far as I am concerned.

I am going to be calling on the Department of Health and

Human Services and the Food and Drug Administration to make

a timely determination whether the continued sale of dietary supplements containing ephedra create an imminent hazard to public

health in our Nation, and if such a determination is made, whether

the sale of these products should be restricted or regulated to protect consumers.

I am also going to work on legislation to develop a commission

for a scientific study to conclusively address the question of the

safety of dietary supplements. I believe, as well, that we need to

establish an effective mechanism for banning the sale of dietary

supplemental products, particularly ephedra and ephedrine-conVerDate 11-MAY-2000 12:52 Jan 16, 2003 Jkt 000000 PO 00000 Frm 00040 Fmt 6633 Sfmt 6633 81314.TXT SAFFAIRS PsN: SAFFAIRS
37

taining supplements to minors. We should draw this line and draw

it clearly.

I want to work as well with consumers, industry and Federal

agencies to establish a mandatory—mandatory—Adverse Event Reporting System that will effectively inform the FDA, consumers,

companies and health care professionals when dangerous products

have been identified.

I believe we should modify the current definition of dietary supplement categories so as to highlight the difference between vitamins and minerals, potent herbal products that act like drugs, and

animal derivatives, as well as exclude steroid precursors, like

andro, from the dietary supplement category.

I am going to press the FDA for the immediate release of good

manufacturing practices and pursue with the Federal Trade Commission ways to further their efforts to eliminate deceptive supplement marketing claims.

I would like to close this hearing by thanking this panel for your

cooperation and your patience as I went off to vote. I want to particularly thank my staff that has been involved in this, Dr. Melanie

Leitner, a congressional science policy fellow, who has worked

harder on this than anybody on my staff. Thank you, Melanie, for

all you have done.

Anne Marie Murphy, Brian McLaughlin, Tom Faletti, Emily

Kirk, Joe Shoemaker, Maria Domanskis, Marianne Upton, and a

team of intrepid interns, thank you all very much for this hearing.

[Whereupon, at 1:18 p.m., the Subcommittee was adjourned.]

(39)

A P P E N D I X

PREPARED OPENING STATEMENT OF SENATOR VOINOVICH

Good morning, and thank you Mr. Chairman for holding this hearing on this topic

which directly impacts the lives of millions of Americans.

While Governor of Ohio, I signed the first law in the Nation establishing a balanced and fair approach to the sale of ephedra. Since then, other States have passed

similar laws, including Hawaii, Michigan, Nebraska, and Washington. In 2000 California passed a similar law, but Governor Grey Davis vetoed the measure because

he believed that the Federal Government should set the standard.

It is my understanding that although the FDA is required by a 1994 law to issue

Good Manufacturing Practice (GMP) standards for the supplements industry; the

agency has yet to finalize these standards. Let me repeat that, 8 years after Congress passed the law, the FDA has not issued the regulations. This is an action the

agency can and must take.

Responsible members of this industry have actively sought appropriate, sciencebased regulation to ensure that consumers are well educated through factual labeling and that dietary supplements are manufactured in a consistent and quality

manner. Additionally, industry has agreed to a ban on the sale of ephedra products

to minors. Unfortunately, not all players in the market are responsible. It is these

bad players that bring us here today.

In our oversight role, we need to ensure that Americans are able to count on existing regulatory agencies to protect and promote their well-being. I hope the work

being done by the National Institutes of Health, even as this hearing takes place,

will help us to understand just where we need to go on this important issue.

Thank you, Mr. Chairman.

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