Note: This is an extended version of an article originally appearing in HerbalGram 61. To read the original article, please click here.

by Mark Blumenthal

On December 30, 2003, the Food and Drug Administration (FDA) announced its intentions to ban the sale of dietary supplements containing the popular but controversial herb ephedra, also known by its Chinese name ma huang (Ephedra sinica Stapf, Ephedraceae).¹

At the press conference, Secretary of Health and Human Services (HHS) Tommy Thompson and FDA Commissioner Mark B. McClellan, MD, PhD, presented the government’s case against herb when sold as dietary supplements. FDA’s forthcoming regulations to ban ephedra were said as being in the final administrative stages and would be published in the Federal Register some time in January, and would go into effect 60 days after its publication, possibly in mid-March. After that date, it will be illegal to manufacture or sell dietary supplements that contain ephedrine and related ephedra alkaloids, including ephedra weight-loss supplements.

FDA also issued a Consumer Alert in which it urged consumers "to stop buying and using [ephedra] products immediately."² Secretary Thompson stated that the reason for the timing of the announcement came from the agency’s wanting to discourage consumers from using supplements containing the herb as millions of people traditionally begin new diet regimens at the end of the Winter Holidays. "The time to stop taking these products is now," HHS Thompson said. "They are simply too risky to be used."

Secretary Thompson and Commissioner McClellan urged retailers, manufacturers and marketers to immediately cease sales of all ephedra products prior to the publication of the rule in January. "By issuing these letters today, we’re sending a strong and unambiguous signal about the safety of dietary supplement products containing ephedrine alkaloids," said McClellan. Consumers should stop buying and using ephedra products right away, and FDA will make sure consumers are protected by removing these products from the market as soon as the rule becomes effective."¹ Curiously, but perhaps predictably, the next day the Associated Press carried a story describing how many consumers who successfully use ephedra-based supplements were stocking up in anticipation of the ban.³

Secretary Thompson said, "First, I am pleased that we were able to take the strong action against ephedra. For too long dietary products containing ephedrine alkaloids have been heavily promoted and widely used. They are simply too risky to be used, whether by people who want to lose weight or by elite athletes seeking to enhance their performance, or by youngsters who want to be like these athletes."⁴

New Legal Framework

Thompson continued, "Second, the regulation that FDA will be publishing will set a new significant legal precedent. For the first time, we will be articulating the legal standard for protecting the public health under the standards of the dietary supplement law which Congress passed approximately 10 years ago [DSHEA]. This is a workable and I think coherent standard that will enable Americans to have access to dietary supplements while enabling FDA to be able to protect consumers from adulterated products."⁴

As intimated by Thompson, HHS and FDA announced the creation of a forthcoming new "framework" for determining if a dietary supplement "presents a significant or unreasonable risk of illness or injury under conditions of use suggested in the labeling or under ordinary conditions of use." The new framework will be published in the upcoming Federal Register notice with the proposed rule.

The impact of the proposed ban on ephedra on other herbs and supplements was unclear. Despite the good safety record of most popular herbs in the U.S. market, the language used in announcing the ephedra ban implicated some of FDA’s long-held irritation with the "burden of proof" provision of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Thompson said that the FDA could not have acted any sooner because DSHEA does not require manufacturers to prove a product safe prior to bringing it to the market. To remove an unsafe supplement from the market, FDA must prove a clear danger to public health. Thompson called this "a tremendous burden of proof’." "We have to prove scientifically that they’re unsafe. That’s a completely different burden of proof that FDA has [than it had prior to DSHEA]. Now, Congress should take a look at whether or not they want that to continue." In response to a reporter’s question, he said that he was not working with members of Congress to change DSHEA, calling it the prerogative of Congress, not HHS or FDA.⁴

[Editor’s Note: The question surrounding FDA’s authority to protect the public against unsafe dietary supplements has been at the core of the debate on ephedra. To clarify this issue, a leading Washington, D.C. regulatory attorney, Stephen McNamara, formerly an attorney for the FDA, has written that, according to federal law, FDA does have adequate authority.⁵]

The issue of FDA’s authority was the subject of editorials in The New York Times and USA Today which both decried the fact that it the ban took too long and suggested that increased safety regulation was necessary.^6,7

In an action related to the announcement, FDA sent letters to 62 firms that market dietary supplements containing ephedrine alkaloids "to give you advance notice of the publication of this rule to facilitate your earliest compliance," and to inform these firms that "FDA intends to begin enforcing the rule as soon as it becomes effective" (i.e., 60 days from the date it is issued).¹ The contents of the letter and the list of companies to whom the letters were are also posted on the FDA’s website (see below).

Questions from reporters sought the identity of additional herbs whose safety may be considered questionable that FDA may consider banning. At the press conference, Commissioner McClellan did not reveal any names, but stated, "Many dietary supplements have important values."⁴

On three separate occasions Secretary Thompson expressed his desire to have the authority to receive [mandatory] reports of adverse events from supplement manufacturers. This position is supported by a Citizen Petition filed by AHPA last March in regard to serious adverse events.⁸

The FDA ban marks the first time the agency has removed a popular dietary supplement from the market under the provisions of DSHEA. "We are going to issue a rule that clarifies and applies a legal standard that that has never been used before. Using the challenging standard provided under the law, we have done all we can to make sure our regulatory action will succeed," said Dr. McClellan.¹

FDA’s actions come after several high-profile deaths of sports figures, most notably the untimely death of Baltimore Orioles pitcher Steve Bechler at a Florida training camp in February 2003. Bechler’s death and previous controversies about the safety of ephedra supplements have resulted in many calls for the ban from Congressional members and medical groups. Numerous professional and amateur sports associations, including the International Olympic Committee, and various branches of the military have banned ephedra supplements. In the past year California, Illinois and New York have banned retail sales of dietary supplements containing the herb.

Last March, FDA proposed strict new warnings for the primary display panel on all ephedra supplement labels.^9,10 At the same time it announced the results of the independent report from the RAND Corporation on ephedra’s risks and benefits.¹¹ Since then FDA has researched all the available scientific literature and has reviewed more than 10,000 public comments that it received in response to its proposal. FDA has apparently attempted create a solid scientific case capable of withstanding a potential challenge in an administrative hearing, as permitted by DSHEA.

Various official documents, press releases, questions and answers on ephedra, the warning letter to the 62 manufacturers, the list of manufacturers, and other communications from FDA related to the ephedra ban are available at <www.fda.gov/oc/initiatives/ephedra/december2003/>.

Industry Response

One of the consistent responses by leaders of the herb industry was that this action validates that many in the industry have been saying for years, that contrary to protestations by previous FDA officials and some members of Congress, FDA does have adequate authority and power to remove dietary supplements from the market that it deems unsafe. "This decision by FDA is evidence that the agency has acknowledged its authority under the current law," said Michael McGuffin, President of the American Herbal Products Association. He added, "AHPA will attentively evaluate the data on which this decision to ban ephedrine-containing supplements was based as soon as that information is available."¹²

"What the ephedra ban proves is that DSHEA works," said David Seckman, executive director and CEO of the National Nutritional Foods Association (NNFA) in a press release.¹³ "The FDA has had the authority since the passage of DSHEA to remove products from the marketplace it deems unsafe. For years, NNFA has urged the agency to use its powers to resolve the debate over ephedra."

It was not clear at press time (January 12) whether any industry group or individual companies would sue the FDA to challenge the ban. Industry veteran Loren Israelsen, executive director of the Utah Natural Products Alliance, a trade group representing manufacturers primarily in the Utah region, was quoted in the New York Times calling ephedra "a political lightning rod." The Times wrote that "Mr. Israelsen said other supplement makers feared that if the F.D.A. did not act against ephedra, Congress would move to tighten the agency’s jurisdiction over all dietary supplements."¹⁴

The Council for Responsible Nutrition’s John Hathcock, PhD. was quoted by the Associated Press as saying that CRN did not oppose a ban, that few companies are still making products with ephedra, and most of CRN members who formerly did no longer do so. "We think the reputable players have found so much controversy and difficulty in this marketplace that they’ve decided to get out of it," AP quoted Hathcock. "We recognize the controversy is a cloud over our whole industry."¹⁵

Exemption for Teas and TCM Practitioners?

One small bit of hope remained for sellers of teas and licensed healthcare professionals who employ ephedra in their scope of practice for uses that are consistent with ephedra’s use in traditional Chinese medicine (TCM) for pulmonary complaints and related conditions. FDA’s website has a "Questions and Answers on FDA’s Actions about Ephedra Dietary Supplements" section that suggests that the Agency will continue to allow ephedra to be dispensed for such conditions as appropriate within the practice of TCM by licensed acupuncturists and doctors of Oriental medicine. The FDA stated, "Essentially all currently marketed dietary supplements will be affected by the rule. The rule does not pertain to traditional Chinese herbal remedies. It generally doesn’t apply to products like herbal teas that are regulated as conventional foods."¹⁶ Such exemptions await clarification in the final rules.

FDA Action Follows Ban in 3 States

The FDA’s ban on ephedra follows previous bans of all dietary supplements containing ephedra (and/or any of its alkaloids, such as ephedrine, pseudoephedrine) by California, Illinois, and New York. The new ban by FDA essentially "trumps" the earlier bans in the three states. Illinois was the first of three states this year to ban ephedra (Ohio banned retail sales of ephedra in 1994, but lifted the ban in late 1996 and Nebraska banned its sale in 1996, reversing the ban in 2001.)

On May 25, 2003, Illinois Governor Rod Blagojevich (D) signed The Ephedra Prohibition Act banning the herb from retail sales as a dietary supplement.¹⁷ Unlike California and New York (see below), Illinois’ legislation does not allow an exception for health care practitioners like acupuncturists to use ephedra/ma huang in formulations as part of their clinical practice. Illinois does permit the sale ephedrine alkaloid-containing products marketed under an OTC monograph or the prescription of ephedra alkaloid-containing drugs by conventional health professionals as explicitly approved by the FDA (i.e., for FDA-approved medical uses).

Illinois is the state where high school football player Sean Riggins died from what the family and local coroner believe were ephedra-related causes. The causality of ephedra in this case has been disputed. An independent review by an expert cardiac pathologist hired by the Ephedra Education Council, a group representing ephedra manufacturers, pointed to infection as the cause of death, according to a letter from Grover M. Hutchins, M.D., Professor of Pathology at Johns Hopkins University.¹⁸ It may not be surprising that Illinois is the first of three states to have banned ephedra, as US Sen. Dick Durbin (D) reportedly had a hand in the action. He has held several hearings on ephedra safety and has introduced a bill into the Senate, The Dietary Supplement Safety Act of 2003 (S 722), a bill that is based on Durbin’s concern’s over ephedra safety.

On October 12 lame-duck California Governor Gray Davis (D) signed into law a bill that will make sales in California of dietary supplements that contain any amount of "ephedrine group alkaloids" a crime as of January 1, 2004.¹⁹ The bill effectively makes any dietary supplement containing the herb ephedra illegal for any purposes unless it is sold by medical prescription.

The California ban, originally introduced on February 20, 2003, as Senate Bill 582 by Sen. Jackie Speier (D-San Francisco/San Mateo), does not affect FDA-approved over-the-counter (OTC) or prescription drugs containing ephedra alkaloids; these drugs will continue to be available in the state by prescription only. (This provision is similar to those in Illinois and New York.) In California licensed health care practitioners are exempt from the restrictions, with the exception that the new law places a statutory restriction on such practitioners’ scope of practice by specifically criminalizing their dispensing of ephedrine-containing supplements for weight loss, body building, or athletic performance enhancement — areas for which ephedra-containing dietary supplements have been popularly marketed. The law specifically stipulates that sale of dietary supplements containing ephedra alkaloids "directly to a licensed health care practitioner" and to "a licensed pharmacist" will continue to be legal only when the product is for the purpose of treatment of patients under the direct care of a health care practitioner. Presumably, "licensed health care practitioner" in California would include licensed alternative healthcare practitioners like acupuncturists and the now-licensed naturopaths,²⁰ so long that the herbal preparations with ephedra are used within the scope of practice defined in the law. The penalty for violation of the law is a misdemeanor with imprisonment in a county jail for not more than one year, or a fine of not more than $1,000, or both. If the violation is committed with intent to defraud or mislead, the violator is subject to not more than one-year imprisonment in county jail of state prison, or a fine of not more than $10,000, or both.

New York became the third state to ban ephedra. The new law, signed by Gov. George Pataki (R) on November 3, provides for a fine of up to $500 for each illegal sale of the supplement.²¹ The law allows ephedra in supplements to be sold on a prescription basis. The ban became effective immediately. The governor had officially signed the legislation into law on August 19, 2003. Effective October 19, 2003, the sale of dietary supplements containing ephedra has been prohibited and violators face fines of up to $500. Exceptions allow ephedra to be included in Food and Drug Administration (FDA)-regulated nonprescription (OTC) drugs and for the sale of the herb ma huang (ephedra) by licensed acupuncturists and practitioners of Traditional Chinese Medicine so long as they are certified by an entity accredited by the National Commission of Certifying Agencies. These practitioners may distribute ephedra within the scope of their practice for appropriate purposes, except for weight loss, bodybuilding, or as an "energy food." The only other exceptions to the ephedra ban in New York are for products that receive "explicit approval as safe and effective for [their] intended use under the Federal Food, Drug, and Cosmetic Act … or [are] lawfully marketed under an over-the-counter monograph" issued by the FDA.

In related moves to limit the availability of ephedra, in May, Florida banned sales of ephedra-containing supplements to minors.²² New Jersey had passed a similar action previously on May 1, 2003.²³ According to the Associated Press broad bans were also been under consideration in Massachusetts, Nebraska, New Jersey and Hawaii.²⁴ although the FDA’s ban would make such moves moot. It should be noted that the American Herbal Products Association policy for ephedra labeling prohibits the sale of ephedra-containing herbal supplements to anyone under 13.^25,26 While this is an industry guideline, it is voluntary and does not have the force of law. Many companies who have been marketing ephedra-containing products are not members of AHPA and have been under no formal requirement to label their products in accordance with the trade organization’s policy, other than the pressures attendant from product liability considerations.

As has been noted in the media and based on the overall findings of RAND report, FDA has had considerable difficulty accumulating adequate scientific support for a ban. The state legislatures, however, are not bound by the same standards of scientific evidence and appear to have responded to the highly publicized ephedra-related deaths, adverse events, and the resulting lawsuits.

Criticized by some for dragging its feet, the FDA is now clearly taking a leadership role. "We are laying the strongest possible foundation to not only take the product off the market, but to keep it off," Commissioner McClellan said at the press conference in December.⁴

References:

1. FDA. FDA Announces Plans to Prohibit Sales of Dietary Supplements Containing Ephedra (press release) Washington, DC: Food and Drug Administration, Dec. 30, 2003.

2. FDA. Consumer Alert: FDA Plans Regulation Prohibiting Sale of Ephedra-Containing Dietary Supplements and Advises Consumers to Stop Using These Products. Washington, DC: Food and Drug Administration, Dec. 30, 2003. http://www.fda.gov/oc/initiatives/ephedra/december2003/advisory.html.

3. Peter J. Ephedra Products Sell Fast Ahead of Ban. Associated Press, Dec 31, 2003.

4. A text of Health and Human Services Secretary Tommy Thompson and FDA Commissioner Mark McClellan on Dec. 30, 2003, as transcribed by eMediaMillWorks

5. McNamara SH. FDA has adequate power and authority to protect the public from unsafe dietary supplements. HerbalGram 1996;38:25-7.

6. New York Times. The ephedra ban is not enough (editorial). New York Times Jan. 5, 2004.

7. USA Today. Law lets risky stimulant take ephedra’s place (editorial). USA Today Jan 6, 2004.

8. AHPA. Citizens petition by the American Herbal Products Association for regulations requiring adverse experience reporting for dietary supplements. Silver Spring, MD: American Herbal Products Assn., Mar. 20, 2003.

9. U.S. Food and Drug Administration. Dietary supplements containing ephedrine alkaloids; Reopening of the comment period Docket No. 95N-0304]. Federal Register Mar. 5, 2003;68(43):100417-20.

10. Blumenthal M. FDA proposes strong warnings for ephedra, releases independent RAND report on ephedra safety and efficacy. HerbalGram. 2003;58:68-70.

11. Shekelle P, Hardy ML, Morton S, Maglione M, Mojica WA, Suttorp MJ et al. Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. Evidence Report/Technology Assessment No. 76 (Prepared by Southern California Evidence-based Practice Center, RAND, under Contract No 290-97-0001, Task Order No. 9). AHRQ Publication No. 03-E022. Rockville, MD: Agency for Healthcare Research and Quality; February 2003

12. AHPA. FDA moves to ban ephedra: final rule due in January. Silver Spring, MD: American Herbal Products Assn., Dec. 30, 2003.

13. NNFA. FDA to ban ephedra. Costa Mesa, CA: National Nutritional Foods Assn., December 30, 2003.

14. Stolberg SG. U.S. to prohibit supplement tied to health risks. New York Times, Dec. 31, 2003.

15. Solomon J. U.S. bans ephedra, drug linked to deaths. Associated Press, Dec. 30, 2003.

16. FDA. Questions and answers on FDA’s actions about ephedra dietary supplements. Washington, DC: Food and Drug Administration, Dec. 30, 2003. <www.fda.gov/oc/initiatives/ephedra/december2003/qa. html>.

17. Ephedra Prohibition Act. 2003 Ill. Laws 8 (May 28, 2003). <http://www.legis.state.il.us/legislation/publicacts/fulltext.asp?Name=093-0008&print=true>.

18. Hutchins GM. Letter to Ephedra Education Council. Jan. 11, 2003.

19. Ephedrine Group Alkaloids. 2003 Cal. Stat. 903 (Oct. 12, 2003). <http://www.leginfo.ca.gov/pub/bill/sen/sb_0551-600/sb_582_bill_20031012_chaptered.pdf>.

20. LaMont S. Doctor of Naturopathy Licensure Law Passes in California. HerbalGram 2004;61:64.

21. An act to amend the general business law, in relation to banning the sale of dietary supplements containing ephedra to persons in New York state. 2003 N.Y. Laws 385. <http://assembly.state.ny.us/leg/?ch=385>.

22. An act relating to weight-loss pills; defining the term "weight-loss pill"; prohibiting the sale or other transfer of weight-loss pills to minors; providing a defense; requiring establishments selling such pills at retail to post notice that such sale is unlawful; providing an effective date. 2003 Fla. Laws ch. 24.(May 21, 2003). <http://election.dos.state.fl.us/laws/03laws/ch_2003-024.pdf>.

23. An Act concerning products that contain ephedrine alkaloids and supplementing Title 24 of the Revised Statutes. 2003 N.J. Laws 57 (May 1, 2003). <http://www.njleg.state.nj.us/2002/Bills/PL03/57.PDF>.

24. Gormley, M. N.Y. becomes third state to ban ephedra. Associated Press, Nov. 3, 2003.

25. American Herbal Products Association. Ephedra trade recommendation. Silver Spring, MD: AHPA, Sept., 2000.

26. McGuffin M. Self regulatory initiatives by the herbal industry. HerbalGram 2000; 48:42.