Ephedra-Based Dietary Supplement Products and Issues For Product Sellers

By Michael D. Shalhoub, Esq., Heidell, Pittoni, Murphy & Bach LLP

This article is adapted from a presentation made by the author to the Pharmacy Liability Sub-Committee of the Medical Liability Committee of the Defense Research Institute in March 2003.

Introduction

Brewing over the past several years has been the possibility of a significant amount of litigation involving nutritional supplements. These products include ephedra, or Ma Huang, which was recently the focus of intense media attention following the death of a professional baseball player during spring training. The death occurred under circumstances that led people to believe that the athlete's use of an ephedra-based weight-loss product contributed to his death. This newsworthy incident renewed ongoing requests that ephedra products be banned from the market, or at a minimum, that they be subject to FDA regulation. There have been calls for congressional action to ban these products, and regional governments such as Suffolk County in New York have passed legislation banning the sale of such products locally.

A political firestorm such as presently exists for ephedra products will inevitably lead to increased litigation involving the manufacturers and purveyors of the products, as well as nutritionists, personal trainers, and physicians or alternative medicine practitioners who may recommend or provide them.

The following commentary will provide an overview of the product, the regulatory scheme, some current developments, and some recommendations regarding the defense of suppliers of these products who may be the subject of litigation. This is not intended to be a comprehensive historical, legal, or scientific discussion of ephedra litigation.

What is Ephedra?

Ma Huang is a Chinese plant whose extract has been used for medicinal purposes, according to reports, for upwards of 5,000 years. Many of its supporters have touted its longevity of use as proof of its safety. This type of logic may be questionable.

Ephedra is an extract of the Ma Huang plant, and it has been used for millennia in China for its respiratory benefits in the treatment of hay fever and asthma. The Indo-Aryan society ate the plant to give strength and happiness, and to combat exhaustion. Though it is reported that the Romans used ephedra, it was not widely used in Europe after Roman times.

In the 1970s, a Danish physician treating asthmatics with an ephedrine compound serendipitously found that his patients experienced weight loss. Subsequent studies by obesity researchers demonstrated significant weight loss when ephedra was combined with caffeine, as compared to placebo.

Through the current time, ephedra-based products are touted as being good for weight loss, energy enhancement, muscle growth, and a host of other beneficial results, including sexual enhancement. However, since the early 1990s, the FDA has been in receipt of reports of side effects, including heart attacks, strokes, and psychoses associated with the ingestion of ephedra products.

Ephedra is big business, with sales of ephedra-based products in 2002 reaching $1.24 billion. Although this figure was down 14% from 2001, likely due to the rash of poor publicity, it shows that a lot of product is sold every year. The ephedra product category has been increasing in volume as well. American Health Line (1), cites 424 million doses sold in 1995, followed by an increase to 3 billion in 1999. A recent survey of 14,000 United States adults indicated that 1% of them had used an ephedra-based product in the previous two years. (2)

Regulatory Background

Products that contain ephedra are considered to be nutritional supplements, not drugs. For years it was unclear whether the FDA had the authority to regulate nutritional supplement products such as products containing ephedra. The FDA’s ability to regulate drugs and food has been unchallenged. Logically, it would seem that the FDA ought to be able to regulate products marketed as having health benefits, like ephedra products. However, that is not our regulatory scheme.

Before being able to sell a drug for a specific use, a drug manufacturer must be able to demonstrate to the FDA that the drug is safe for that intended use. In general, the manufacturer must also demonstrate to the FDA that the drug's labeling is accurate and complete.

Congress, however, created a different and much less stringent regulatory framework for nutritional supplements (like ephedra-containing products). In 1994, Congress passed the Dietary Supplement Health & Education Act (DSHEA). Basically, the manufacturer of a nutritional supplement product complies with DSHEA by positioning its product in such a way that it makes no claims that the product will treat specific diseases, and by adding label statements that the FDA has not studied or approved the product, and that the product is not “intended to diagnose, treat, cure or prevent any disease." Pick up almost any popular magazine, walk down the aisles of the pharmacy sections of large supermarkets, chain drug stores or health food stores, or even a local health club, and you will see ads for ephedra products and product labeling that fits within this broad regulatory framework.

From its enactment, the DSHEA has been subjected to significant criticism, and the FDA has chafed against its restrictions. Particularly for ephedra products, the FDA has been vocal in its criticisms. In 1997, the FDA made it clear through proposed regulations (3), which never went into effect, that it wanted to regulate the ephedra market via labeling that limited ‘serving’ size, limited recommended daily consumption, and limited the length of time that the product should be taken. In addition, labeling was requested to warn against the use of ephedra-based products during pregnancy and in other health conditions, and to caution against its use with certain products such as caffeine. At the time that these regulations were proposed, the FDA found on the market some 125 ephedra-based dietary supplement products, which were being marketed for uses such as weight loss, body building, increased energy, improved mental concentration, increased sexual sensations or euphoria, or as alternatives to illicit street drugs.

( 4) The FDA reviewed the AERs and concluded that the most common complaints were of symptoms that were consistent with the known pharmacologic and physiologic effects of ephedra. The FDA felt that even in the absence of a case-controlled study demonstrating causation in a statistical manner, the nature of the reviewed evidence demonstrated causation to the FDA’s satisfaction.

Nonetheless, the General Accounting Office issued a report in 1999 which concluded that the FDA did not have sufficient scientific evidence to support the regulations that it wished to promulgate. (5)

In June 2002, President Bush, to some criticism, directed a complete review of the issue of whether ephedra-based dietary supplements should be banned. The review was to be done by the Rand Corporation and subsequently evaluated by the National Institutes of Health to determine if additional study was necessary. (6)

In February of 2003, a New York Congressman announced plans to introduce legislation that would allow the FDA to regulate ephedra.

State and local governments have already acted to regulate and limit the sale of ephedra-containing products. Nassau County, New York, banned ephedra products except for weight loss and body building purposes. The New York State Department of Health banned twenty specific ephedrine products being marketed as street drug alternatives. Florida banned all non-medicinal uses of ephedrine. Tennessee and Louisiana restricted ephedrine to prescription use only, with some exceptions. Ohio requires that a licensed pharmacist dispense ephedrine products and that purchasers be at least 18 years old; cold and flu ephedrine products are excepted. (7)

Current Events

The NCAA, National Football League, and the International Olympic Committee prohibit the use of ephedra-containing products. Major League Baseball does not ban the product, with its players' union arguing that legally available products should not be denied to baseball players. The American Medical Association in October 2002 made clear its position that ephedra-containing diet products should be removed from the marketplace because the risk-benefit ratio for those products was felt to be unacceptable. Canada issued an advisory to its citizens not to use products containing ephedra or ephedrine.

By February 2000, the FDA had received 1,398 reports of adverse events associated with ephedra, with 81 deaths and 32 heart attacks. (8). In the wake of the baseball player's death in 2003, The FDA is contemplating further action as to ephedra products. (9).

In November 2000, the New England Journal of Medicine released on its web site, not waiting for subsequent publication of the article, the results of a study showing that out of 140 reports of serious problems with ephedra-containing products, 87 cases were definitely, probably, or possibly linked to ephedra products. In the published article, the authors concluded, “The use of dietary supplements that contain ephedra alkaloids may pose a health risk to some persons. These findings indicate the need for a better understanding of individual susceptibility to the adverse effects of such dietary supplements.” (10)

As of 2003, the FDA has received reports of nearly 100 deaths reportedly associated with ephedra products. (11) A 2003 article arising out of the Hemorrhagic Stroke Project at the University of Texas (12) concludes that ephedra was not implicated in increased risk of hemorrhagic stroke, except perhaps at higher doses than recommended. An article in the March 2003 Annals of Internal Medicine (13) reports that the United States Poison Control Centers recorded 1,178 adverse reactions to ephedra products in 2001. (14). Of course, demonstration of association is not proof of actual medical causation.

In 2002, the United States Attorney General announced a criminal investigation of Metabolife, an ephedra product manufacturer, in regard to statements by the company president denying awareness that its products had caused significant side effects. The government alleged that the statement was false and the company had received thousands of complaints of side effects. The company’s position was that the statement was, and is, true – that its products have never been proved to cause significant side effects.

In 2002, one company admitted receiving almost 14,000 adverse event reports since 1995 concerning ephedra, but disputed causation between the reported events and the ephedra product. (15). In November 2002, an Alabama jury awarded $4.1 million to four people who suffered strokes or heart attacks after taking an ephedra-based appetite suppressant. (16). In January 2003, a federal district court judge in Ohio allowed a proposed class action to survive a motion to strike class action allegations. Some parts of the complaint were dismissed, but others were allowed to stand, at least at a preliminary stage. Delahunt v. Cytodyne Technologies, 2003 U.S. Dist. Lexis 1477 (1/24/03). Of note, product sellers and suppliers are defendants in that suit. Metabolife presently faces more than 100 suits alleging personal injury involving its products. (17).

The manufacturers maintain that the products are safe when used in accordance with their labeling. They take the position that nearly 30 studies show no adverse events and limited side effects from ephedra-based drugs. (18).

However, manufacturers have been feeling the legal and market pressures against ephedra and have been responding. In November 2002, Twinlab Corporation announced plans to switch to non-ephedra supplements by 3/31/03. Also in November 2002, General Nutrition Centers stopped selling ephedra products to minors. In January 2003, EAS, a manufacturer of ephedra products, chose to halt production of the products. Also in January 2003, 7-Eleven directed its franchisees to remove ephedra products from its shelves. (19).

Legal Issues

A comprehensive discussion of the legal issues to be faced by potential defendants is beyond the scope of this article. Anyone representing pharmacies or suppliers of these products should consider the following issues while developing the legal defenses in each case:

• Proximate cause - general causation and specific causation - must be completely evaluated by obtaining the pertinent medical literature, medical records, and reviews by appropriate experts.
  
  Consider the relationship between the seller and the customer in the individual client’s case. Is there something more than the plaintiff simply walking into the store, picking up a product from the shelf, and buying it? Was there interaction and discussion between the plaintiff and the store’s employees? Was the plaintiff steered to a particular product? Was there a discussion about other supplements or medications that the plaintiff was taking?
  
  Did the supplier recommend literature to the plaintiff to assist the plaintiff in making decisions?
  
  In circumstances where the store is providing counsel and advice to its customers, what training and quality control exist in regard to what the employee tells the customers?
  
  What manufacturer's advertising is placed in the store or in the marketplace by the supplier, and why is that advertising chosen over some other advertising?
  
  Does the store make its own written materials available for customers considering different products to assist them in making choices between products? Do the sales people assist the customer in making choices between products?
  
  The liability issue may boil down to whether the client’s operation is the type in which there is no store input regarding the customer's choice of product or the type in which the client provides significant input into the customer's choice of product: The more client input for customer decisions, the greater the likelihood of liability independent from that of the manufacturers.
  
  Be aware that there may or may not be the same type of cooperation between retailers and manufacturers that is customary in other pharmaceutical litigations. The lawyer representing the company that manufactured the product purportedly taken by the deceased baseball player stated: “It is difficult for us to reach out into the marketplace and control what retailers do. We strongly recommend that all consumers read and follow the label instructions prior to use.” (20)
  
  Does state law permit the sale of such products over the counter? Was the product in question among those appropriate to be sold in this state?
  
  Does the client advertise these products, and if so, what do the advertisements say? Analyze how the advertisements will affect defense issues.
  
  What is the client's relationship with the manufacturer? Can the manufacturer be persuaded to assume the client’s defense? Are there independent claims being made against the client that prevent an assumption of the defense?
  
  Are there contracts between the client and the manufacturer?

Ironic Questions

" To quote a journalist on this issue, “If ephedra is so good to avoid, why sell it at all?” (21)

With chain stores filled with branded products such as CVS toothpaste, or Duane Reed aspirin, or Eckerd’s ibuprofen, why do we not see the chain stores branding ephedra products? As with the first ironic question, a journalist must be credited for raising this question. (22)

(22) References

1. Ephedra. Akron Beacon Journal examines herbal supplement. American Health Line. 2003. Available on Lexis.

2. Morgenstern LB, Viscoli CM, Kernan WN, Brass LM, Broderick JP, Feldmann E, Wilterdink JL, Brott T, Horwitz RI., Use of Ephedra Containing Products and Risk for Hemorrhagic Stroke. Neurology. 2003 Jan 14;60(1):132-5.

3. Federal Register. 1997;62(107).

4. http://www.cnn.com/health/9908/04/ephedra.safety/

5. http://www.cnn.com/health/9908/04/ephedra.safety/

6. The Washington Post. June 15, 2002.

7. Dietary Supplements, Can the Law Control the Hype? 37 Hous. L. Rev. 1249. 2000.

8. American Health Line. May 8, 2002. Available on Lexis.

9. American Health Line. February 20, 2003. Available on Lexis.

10. Haller, C., Benowitz, N., Adverse Cardiovascular and Central Nervous System Events Associated with Dietary Supplements Containing Ephedra Alkaloids. New England J. Med. 2000;343:1833-1838.

11. Medical Letter on the CDC and FDA. March 2, 2003. http://www.newsrx.net/scripts/get_partial.cgi/?file=ISSUESDC.HTML

12. Use of Ephedra containing product and risk for hemorrhagic stroke. Neurology. 2003;60:132.

13. Annals of Internal Medicine. www.acponline.org/journals/annals/ephedra.htm

14. Medical Letter on the CDC and FDA. March 2, 2003. http://www.newsrx.net/scripts/get_partial.cgi/?file=ISSUESDC.HTML

15. Obesity, Wellness and Fitness Week. November 16, 2002.

16. Medical Letter on the CDC and FDA. March 2, 2003. http://www.newsrx.net/scripts/get_partial.cgi/?file=ISSUESDC.HTML

17. http://espn.go.com/mlb/s/2003/0221/1512395.html

18. Chain Drug Review. October 29, 2002.

19. http://espn.go.com/mlb/s/2003/0221/1512395.html

20. New York Times, Westchester Weekly. February 23, 2003;14:5.

21. http://espn.go.com/mlb/s/2003/0221/1512395.html

22. Eder, R. Ephedra Flap could put Category on Diet. Drug Store News. July 22, 2002;24.

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