Supplements supply dietary danger, as FDA looks on.

Dietary supplements may contain the ingredients of a recipe for disaster. Supplements can be dangerous or even deadly, but they rang up over $4 billion in sales last year.

The flood of supplements into the market is attributed to passage of the 1994 Dietary Supplements Health and Education Act (DSHEA). The legislation created a new category, separate from drugs or food, encompassing any "dietary supplement for use by man to supplement the diet."

Drugs must be proven safe in clinical studies and authorized by the FDA before they are marketed, but the agency does not test or authorize dietary supplements. Manufacturers are responsible for providing the information to back their safety claims. The burden is on the FDA to prove products are unsafe before it can act to remove them from store shelves.

"The DSHEA was passed without people realizing what the significance would be in terms of tying the FDA's hands," said Virginia Buchanan of Pensacola, Florida, the plaintiff's attorney in a suit against the manufacturers and distributors of an herbal supplement containing ephedrine. The suit charged that the product caused fatal cardiac arrhythmia in a college student. (Schlendorf v. Alternative Health Research, Inc., No. 3:97-CV-104-RV(SMN) (N.D. Fla. settled May 20, 1998).)

Some herbal products contain chemicals as potent as any drug. An Associated Press analysis of FDA records found over 2,500 reports of side effects such as dizziness, nausea, and heart palpitations and 79 deaths associated with dietary supplements. (Unregulated Dietary Supplements Can Be Risky, CNN Interactive (Feb. 22, 1998) http://www.cnn.com.)

Without government regulation, the purity of supplement ingredients cannot be guaranteed, and consumers may harm themselves if they believe "more is better" and exceed manufacturer-recommended doses. Without studies, it is not known if a product can be harmful at greater concentrations or dosages or in combination with other ingredients or medications.

Another question: What is the distinction between herbal products with naturally occurring chemicals as potent as those found in any drug and the drugs themselves?

"A synthetic form of ephedrine is used in hospitals, and it performs the same action and has the same components as the herbal variety," said Buchanan. Even if a product is "all-natural," she said, if it acts like a drug, it should be tested and regulated like a drug.

Some of these issues are being taken up in the courtroom. Consumers have filed suits alleging products liability and personal injury. Class actions are seeking damages from makers and distributors of dietary supplements. In addition, manufacturers are legally challenging the FDA's regulatory authority.

Super Dieter's Tea is one dietary supplement embroiled in litigation. The first in a consolidated group of four wrongful death cases filed in San Francisco County Superior Court charged fraud, negligence, strict products liability, and breach of warranty against the tea's manufacturer.

James Porter's wife died after drinking the tea, which contained senna and other diuretic/laxative herbs that allegedly can leach electrolytes from the body, triggering cardiac arrest. (Porter v. Laci Le Beau, No. 531430-7 (Cal., San Francisco County Super. Ct. filed Mar. 29, 1995).)

The jury concluded the product was defective and failed to carry the proper warning, but it did not find medical causation, according to plaintiff's attorney Christopher Grell.

"People within the medical profession have to become aware of the potential adverse short-term and long-term side effects," said Grell. "Nobody's taught about herbs in medical school."

One dietary supplement that has been proven dangerous is ephedrine, which stimulates the heart and nervous system like an amphetamine. Ephedrine is blamed for 44 deaths and 900 illnesses and has been banned as an ingredient in supplements in New York and Florida.

A class action against the maker and distributor of Ma Huang, an herbal product containing ephedrine, is pending. Plaintiffs claim they suffered circulatory and cardiovascular injuries after ingesting the product. (Nanney v. General Nutrition Corp., No. 95-0160 CVKEHOE (S.D. Fla. filed Jan. 26, 1995).)

The FDA is reviewing comments on regulations proposed in June 1997 that include capping the maximum dose of ephedrine at 24 mg per day, banning the combination of ephedrine with caffeine or other stimulants, labeling the product with the warning "taking more than the recommended serving may result in heart attack, stroke, seizure, or death," and forbidding the marketing of ephedrine supplements as weight-loss or bodybuilding agents.

"The FDA is dragging its feet," said Grell. "The FDA acknowledges the American public consumes billions of dollars of [dietary supplements] with the assumption they've been tested and are safe for consumption, and the FDA also recognizes this is an erroneous assumption," said Grell. "But people aren't aware of the implications, and the FDA has done little to educate the public."

FDA enforcement

Regulations issued under the DSHEA state that dietary supplements must be labeled as such. Supplements may make "structure or function" claims--claims that the product affects a system in the body (such as "supports the immune system")--without seeking FDA approval. But the claim must be printed on package labeling followed by the disclaimer, "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease."

Grell says this is not strong enough. "We need a labeling provision to tell consumers this product has not been approved as safe by the FDA," he said. "That statement can be interpreted by consumers that the product has at least been tested, and it probably hasn't."

The FDA says only if a dietary supplement expressly or implicitly makes a "disease claim" can it regard the product as a drug that must meet safety and effectiveness standards before marketing.

Operating under DSHEA regulations, the FDA has had limited success withdrawing products and enforcing label claims.

In 1997, the FDA forced the manufacturer of Nutrition 21, a supplement containing chromium picolinate, to stop using "disease claims" that the product caused long-term weight loss, lowered blood cholesterol, or treated or prevented diabetes.

The agency is also taking steps to remove "herbal fen-phen" from the market. It considers these products to be unapproved drugs because their names reflect that they are intended for the same use as the anti-obesity drugs fenfluramine and phentermine. The FDA has banned fenfluramine from the market. Most herbal fenphen products contain ephedrine as a main ingredient. Some have a compound closely related to L-tryptophan, a dietary supplement removed from the market in 1990 when it was linked to over 1,500 cases of a blood disorder.

The FDA's regulatory powers under the DSHEA are being tested by manufacturers. The first challenge involves a dietary supplement promoted as lowering cholesterol.

"This case is going to determine the extent to which companies can imitate prescription drugs and avoid the approval process," said William Schultz, FDA deputy commissioner for policy.

The supplement at issue, a powdered strain of rice fermented with red yeast, is imported from China and sold as Cholestin by Pharmanex, of Simi Valley, California. In late 1997, FDA authorities impounded 10 tons of the rice, calling Cholestin an illegal, unapproved drug since it naturally contains lovastatin, the key component of Mevacor, a cholesterol-lowering drug.

Pharmanex filed a motion for a preliminary injunction against the FDA, saying lovastatin occurs naturally in the rice. The company also argued that Cholestin is more like a food than a drug and was developed to be a food supplement.

In June, a U.S. district court judge in Salt Lake City ordered the FDA ban on imports lifted. Judge Dale Kimball ruled Cholestin was a dietary supplement, not a drug, and Pharmanex would suffer irreparable injury if the ban was upheld. Kimball found the company "raised substantial and serious questions regarding the lawfulness of FDA's interpretation" of the DSHEA, and pointed out that the FDA did not consider the supplement to be dangerous. (Judge Lifts Ban by FDA on Imports of a Special Rice, Wall St. J., June 17, 1998, at B1.)

The FDA had argued, "Cholestin is not a dietary supplement because lovastatin was not marketed as a dietary supplement or food before the FDA approved Mevacor as a drug." The agency is reviewing the court order.

For now, as long as a product is called a dietary supplement, manufacturers and distributors have free reign in testing and marketing it. The supplement industry has a powerful lobby, and regulatory constraints may be slow in coming. But some supplement makers have cooperated with the FDA and are trying to educate consumers about their products.

Manufacturers are working with the FDA to withdraw from commercial distribution "Chomper" and other dietary supplements containing plantain--not the tropical fruit, but a weed used in herbal laxatives-because it may be mislabeled and contain digitalis, a plant with a powerful heart stimulant component that can cause cardiac arrest.

Treasure Box Products, Inc., has voluntarily recalled "Sleeping Buddha" from stores in the United States. Sleeping Buddha contained an unlabeled, prescription-strength drug ingredient estazolam, a derivative of the benzodiazepine family known to have serious side effects.

The Council for Responsible Nutrition, an organization of dietary supplement manufacturers and suppliers, has developed Good Manufacturing Practices (GMPs), which the FDA is reviewing while considering mandatory industry GMPs.

Next steps

A presidential commission formed by DSHEA directive recommended further studies on whether consumers want labeling on supplements and will follow package directions. It urged the FDA to take action when product safety questions arise and to work with the dietary supplement industry to develop warning labels for products.

Litigation may be one way to ensure manufacturers take responsibility for quality control of ingredients and proper labeling. Public awareness of the dangers of misuse can also go a long way toward ensuring that safe dietary supplements are sold and used.

"Hopefully, the FDA can use depositions and trial documents as ammunition to prove how little manufacturers know about their own products and how little the public knows," said Buchanan.

"It's going to take doctors asking their patients questions, making the association and getting suspicious about the involvement of supplements, and reporting it to the FDA," said Grell. "And it will take someone at the FDA being accountable."

The Special Nutritionals Adverse Event Monitoring System posts reports of illnesses and injuries attributed to special nutritional products, including dietary supplements, on the Web. The site, run by the FDA-sponsored Center for Food Safety and Applied Nutrition, can be found at http://vm.cfsan.fda.gov/~dms/aems.html.

Adverse effects of dietary supplements may be reported by calling the FDA's MedWatch line, (800) FDA-1088. The FDA's Web page address is http://www.fda.gov.