Herbal supplements may be dangerous.

Supplements may look like magic bullets for health problems. But users may be playing Russian roulette.

Anne Marie Capati, a 37-year-old mother of two, goes to the gym every morning at 6 a.m. The gym convinces her to pay extra to get a "trainer-nutritionist." He gives her a list of herbal supplements and vitamins to take and even takes her to a special shop to get them. She tells him she suffers from high blood pressure and is taking prescription medicine. He says exercise should help reduce her pressure.

In total, the trainer has her taking 11 different substances daily, including ephedra (ma huang), yohimbe, phenylalanine, guarana, and willow bark. One morning she reports a headache and shortness of breath. The trainer urges her to exercise harder. She passes out and dies a few hours later.

Capati suffered intracranial bleeding due to elevated blood pressure. In a lawsuit filed by her husband, my firm claimed the bleeding was caused by the combination of ephedra with other substances.(1)

This is not the only tragedy associated with the herb ma huang. The FDA has reported about 40 deaths and hundreds of serious injuries--primarily involving cardiovascular problems--due to its use.(2) Nor is ephedra the only dangerous herbal supplement available on the shelves of drugstores, supermarkets, and convenience stores nationwide. There are dozens of herbal products known to be potentially toxic.(3) For instance, consumers can buy willow bark labeled as "aspirin-free," which might sound good to a mother worried about her children developing Reye's syndrome from taking aspirin. However, willow bark converts to aspirin in the body.(4) There is no warning to this effect on the label.

Herbal supplements are just one variety of dietary supplements that have been linked to injuries.(5) Herbal and other dietary supplements have become a gigantic business in the United States, with more than $6.5 billion in sales in 1997.(6)

About 100 million people take a dietary supplement regularly. Yet few people can give sound reasons for taking supplements, and fewer know what side effects have been associated with their use. Users uncritically accept the claimed benefits and tend to believe the product is a magic bullet that will cure their problem. Some people even say supplements are good medicines that doctors don't prescribe because they work too well.

The Dietary Supplement Health and Education Act of 1994 (DSHEA) unleashed dietary supplements on the American public.(7) This is the place for lawyers to start if they are contemplating suits on behalf of people injured by these products. Before 1994, dietary products were in limbo. The FDA asserted it could regulate them and sought to place the burden of proof of safety and efficacy on suppliers. The DSHEA substantially diminished federal control over these products, as compared to food and drugs, which are subject to strict regulation and testing by the FDA.

Under the DSHEA, dietary supplements are defined as products that are intended to supplement the diet (a vague concept) and that contain herbs or other botanical substances, amino acids, vitamins or minerals, or a combination of these.(8) Any product that meets the definition can be sold in stores, and its supplier can make healthlike claims as long as it has scientific evidence for them.(9)

Manufacturers of herbal products either select brand names or use words on labels and in promotional materials to suggest the impossible: "fat burner" or "detoxifies." Consumers can buy "natural Viagra," the "# 1 rated herbal" for impotence. Its ad attracts readers by saying it contains a "secret ingredient" that has been "recently praised in N. Y. Times."

Any trip to the drugstore will show that manufacturers of herbal and like products have embraced the liberty to make health claims on labels. The label can state the way the product is intended to affect "the structure or the function" of the body but cannot claim its use for a specific disease.(10) Manufacturers just say a product is intended to promote wellness" rather than treat "sickness." For example, a manufacturer may claim its product "promotes regularity" instead of"treats constipation." Echinacea gets away with saying coyly that it promotes well-being "during the flu season."

Effectiveness is another concern. There is often little or no scientific proof that supplements help with the condition for which they are promoted. Further, someone who relies on the promise of an herbal might decide to forgo seeing a doctor for a needed treatment.

Often the amount of herbal substances a supplement contains is so slight that it would not have any effect on the body even if the herb was beneficial.(11) Nor does a statement that the botanical product is "natural" have any meaning; after all, a toxic mushroom is natural. Former FDA Commissioner David Kessler said effectiveness of supplements today is measured by the amount of sales.(12)

The FDA, said Kessler, is now chasing horses once they're out of the barn. As a result of the DSHEA, the burden of proof has shifted to the agency to demonstrate on a case-by-case basis that a dietary supplement represents an imminent danger to health or a significant or unreasonable risk of illness or injury.(13)

To its credit, the FDA has sought to stop its role in preventing injury from being swept away by the DSHEA. It has advocated that nutritional statements appear on labels, which must also read, "This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease."(14)

The Food and Drug Administration has also proposed requirements about good manufacturing practices (GMP), although unsanitary manufacturing is not the problem. If GMP also led to dosage standardization, that would be a help.(15) The FDA has used its considerable public relations powers to warn the public about risks from dietary supplements, and it maintains a Web site on the subject.(16)

Some of the herbals the FDA has warned about on its Web site are St. John's wort, sold as "herbal Prozac"; CHOMPER, marketed as an "herbal laxative" and containing poisonous plants, which caused a heart vessel blockage in a user; and "herbal fenphen," which came out after the recall of fenfluramine and contains a mixture of herbs, including ephedra, St. John's wort, and 5-HTP.

Fighting back

The FDA began opposing the use of ephedra in 1997. After holding extensive hearings, it proposed regulations for labeling ephedrine alkaloids, advising no more than 8 mg "per serving," a daily consumption of no more than 24 mg, and use for no more than seven days.(17) In addition, warnings against use during pregnancy or in the presence of other health conditions were proposed. However, demonstrating the power of the supplement manufacturing industry, no regulations have yet been promulgated.

The states have some power to ban or regulate dietary supplements, just as they have done with some controlled substances such as the weight-loss drug combination fen-phen.(18) For example, ephedra is banned in at least 17 states when sold in combination with other substances that users might take to get high (for example, ephedra is an ingredient in Ecstasy).

As state medical boards recognize the health hazards of supplements, they may step up their regulatory activities. The Federal Trade Commission, which regulates product advertising, also has powers--infrequently exercised--to prevent false advertising, including statements on the Internet.

Many critics of herbals and other supplements have addressed the risks in print and on the Internet.(19) However, the manufacturers and sellers of these products are drowning out these words of caution. Information found on the Web often demonstrates a supplier's spin.

A search query for any herb will return many hits--almost all extolling the product, some far beyond what the law allows, and most selling the product from the Web site. (This is how we obtained much of the information that was useful for the Capati suit.) Even the Physician's Desk Reference offers an annual publication on herbs. The book is more of a promotion than a list of risks and benefits.(20)

Few medical articles in peer-reviewed journals report controlled tests on herbals that showed health benefits. On the other hand, the medical literature documenting injuries from these products is solid.(21) A review of this literature shows that the risks of morbidity and mortality associated with supplements lie especially in combination situations--combining various supplements, taking them with a prescription drug, or taking them when there is an underlying disease.

These situations were all apparent factors in the death of Anne Marie Capati. Besides ephedra, other herbals that may be dangerous in combinations, as reported in the medical literature, include garlic and gingko, which may cause problems if taken with anticoagulants; bilberry, which may interfere with diabetes therapies; Echinacea, which may make such drugs as steroids and methotrexate more damaging to the liver; St. John's wort, which may be risky if used with monoamine oxidase inhibitors (MAOI); and kava, which may cause coma when taken with alprazolam.(22)

Manufacturers say supplements are natural herbs and make romantic references to "Chinese herbs used for centuries" supposedly without problems. But the "test of time" is no guarantee that any folklore herb is free from risk.

These products are not available in standard dosages since they are not purified to meet standards. A recent study by the Good Housekeeping Institute showed that one herbal product as sold by various companies came in varying strengths, one containing 17 times as much herbal substance as others.(23) And there is no agreement on proper dosages for the various conditions the herbal supplements are purported to treat.

Another argument made for herbals is that they are no different from drugs. Ephedra is a prime example. Suppliers state it is the "same" as ephedrine, which is FDA-approved for use in cold medicine. The comparison is misleading--ephedrine is a synthesized drug of known purity; ma huang is the leaves from a plant made into a product put in a capsule. Studies show that ephedra contains a number of chemicals and ephedrine alkaloids and is far from pure ephedrine.(24)

Litigation 

The bar has not missed the potential for liability involving herbal supplements. Recently, supplement manufacturer Alternative Health Research, Inc., settled a case involving the death of a 20-year-old college student who took "Ultimate Xphoria Herbal Supplement." It contained ephedra and had inadequate warnings about the product's use with an MAOI. The young man died from cardiac arrhythmia.(25)

In a case involving supplements, the most obvious defendants are manufacturers. There may be a good products liability cause of action for failure to warn of risks and contraindications, and there will probably be issues of efficacy and overpromotion. At the least, attorneys can argue that with the freedom given to suppliers by the DSHEA came concomitant responsibility to the consuming public. Merely stating on a label that the FDA has not approved any claims is not enough.

There may be liability for impurity. The infamous L-tryptophan litigation in the early 1990s illustrated the harm that can be wrought by producing an amino acid through genetic modification. Thousands of American consumers were injured, some of them permanently, from an impurity in this supplement.(26)

Liability for impurity should also cover off-strength preparations, in which the amount of an herb in the actual pill differs from the amount indicated on the label. As discussed above, studies show that there can be tremendous dosage variations in the supplements.

The suppliers and promoters of herbal products are also potentially liable.(27) While the manufacturer is not allowed to say what disease herbal remedies allegedly treat, sellers are not shy about making claims, most of them unsubstantiated by valid medical research.

It is not uncommon in health food stores to find publications that describe which herbs to take for various diseases. The profiling duty that drugstores have when filling prescriptions may be extended to over-the-counter purchases if the pharmacist recognizes incompatibility between the supplement and a prescription drug the person is using.(28)

Nutritionists, diet advisers, trainers, and others who encourage the use of supplements should not be above the law. Often they call themselves specialists and charge for their advice, which makes them responsible for knowing the nature and risks of the substances they are recommending.

"Nutritional malpractice" claims of this sort are a major part of the Capati suit. We allege the trainer-nutritionist for whose services our client's wife paid was not knowledgeable about the interactions of the supplements he recommended, let alone how they would work in a person with high blood pressure.

In many states, people can call themselves nutritionists without having any credentials or certification. Nutritionists or dieticians who have had formal training and pass tests are licensed or certified by the state, but people with this training are not likely to work in fitness centers. Instead, trainers may be certified by one of several national organizations, such as the American College of Exercise or the Aerobics and Fitness Association of American.

Lawyers should investigate what training and experience are required for professional certification. The policies of each group are also important--for example, whether someone who is "certified" may recommend herbal supplements.

Occasionally, supplement cases may contain elements of malpractice on the part of physicians. Doctors have a duty to ask what substances their patients are taking, and they know or should inform themselves about drug and disease interactions with supplements.

But physicians may fail to ask what supplements patients are taking. And patients, when asked what drugs they are taking, may not mention supplements--sometimes because they are embarrassed to tell the doctor they are self-medicating.

Plaintiff attorneys can do a distinct public health service by becoming aware of what risks herbal supplements present. Attorneys should know the causes of action that may accrue when innocent users of these products are seriously injured.

Notes

(1.) Capati v. Crunch Fitness Int'l, No. 113218 (N.Y. Sup. Ct. filed June 28, 1999). Among the defendants is SportPharma USA, Inc., which sold the product Thermadrene as a "fat burner." It contained 20 mg of active ephedra, plus 150 mg guarana seed, 80 mg caffeine, 75 mg purple willow bark, 60 mg cayenne pepper, and 40 mg ginger root.

(2.) In 1996, the FDA issued a warning about ephedra's side effects and set up a special hotline. It said it had received more than 600 reports of side effects with ephedrine alkaloids, mostly in the cardiovascular system. FDA Statement on Street Drugs Containing Botanical Ephedrine, HHS NEWS, Apr. 10, 1996; see also CDC Report on Adverse Effects of Ephedra and Its Ephedrine Alkaloids, MORBIDITY & MORTALITY WKLY.REP. 689 (1996); S.J. Nightingale, Warning Issued About Street Drugs Containing Botanical Sources of Ephedrine, 275 JAMA 1534 (1996).

(3.) L.G. Miller, Herbal Medicinals: Selected Clinical Considerations Focusing on Known or Potential Drug-Herb Interactions, 158 ARCHIVES INTERNAL MED. 2200 (1998) (excellent article with hundreds of citations to the literature); ANDREA PIERCE, PRACTICAL GUIDE OF NATURAL MEDICINES (1999) (recognizes risks). In Germany, a commission has made a detailed safety study. THE COMPLETE GERMAN COMMISSION E MONOGRAPHS (M. Blumenthal ed., 1998).

(4.) See PIERCE, supra note 3, at 667.

(5.) For example, the FDA recently issued warnings about the use of gamma butyrolactone (GBL) and sought to pressure suppliers into voluntarily recalling the product. The FDA contended that it was in fact a drug and had been associated with a death and some serious injuries. FDA Warns of Risks from GBL Marketed as Dietary Supplement, 10 PROD. LIAB. L. REP. 34 (1999). In 1998, the FDA warned against taking the dietary supplement "Sleeping Buddha," an imported Chinese product sold as a sedative that contained a type of prescription-strength benzodiazepine. FDA Warns Consumers Against Taking Dietary Supplement "Sleeping Buddha," FDA Press Release (Mar. 10, 1998), available at http://vm.cfsan.fda.gov/~lrd/hhbuddha.html.

(6.) See Miller, supra note 3, at 2201.

(7.) Pub. L. No. 103-417, 108 Stat. 4325 (codified in scattered sections of 21 U.S.C.).

(8.) 21 U.S.C.S. [sections] 321.

(9.) 21 U.S.C.S. [sections] 343(r)(1)(8).

(10.) Paula Kurzweil, An FDA Guide to Dietary Supplements, FDA CONSUMER (Jan. 1999) (visited Aug. 11,1999), http://vm.cfsan.fda.gov/~dms/fdsupp. html.

(11.) See Herbal Rx--The Promises and Pitfalls, CONSUMER REP., Mar. 1999, at 44.

(12.) Remarks at Good Housekeeping-sponsored consumer safety symposium on herbal remedies, available at Hearst Communications,A Hard Look at Herbal Remedies (visited Aug. 15, 1999), http:// homearts.com:80/depts/health/38ghsy11.htm.

(13.) See Tod L. Stewart, Note, Getting High with a Little Help from the Feds: Federal Regulation of Herbal Supplements, 6 J. PHARM. & L. 101,108 (1996). When the FDA did try to crack down on a new herbal substance, the District of Columbia Circuit Court sustained an appeal by a supplier who attacked the regulations as exceeding the agency's authority. Pearson v. Shalala, 164 F.3d 650 (D.C. Cir.), reh'gen banc denied, 172 F.3d 72 (D.C. Cir. 1999). But see Nutritional Health Alliance v. Shalala, 144 F.3d 220 (2d Cir.), cert. denied, 119 S. Ct. 589 (1998).

(14.) 21 U.S.C.S. [sections] 343.

(15.) See 21 U.S.C.S. [sections] 342. United States Pharmacopeia (USP) has a status fact sheet regarding botanicals at http://www.usp.org. It is working on standards for contents and purity in herbals.

(16.) http://vm.cfsan.fda.gov/~dms/supplmnt.html

(17.) Dietary Supplements Containing Ephedrine Alkaloids, 62 Fed. Reg. 30678 (1997). This report summarized hearing testimony and the medical literature on adverse reactions with ephedrine and listed many adverse reactions. In August 1999, however, a study commissioned by the House Committee on Science criticized the FDA as being too tough on ephedra. U.S. GEN. ACCOUNTING OFFICE, DIETARY SUPPLEMENTS: UNCERTAINTIES IN ANALYSES UNDERLYING FDA, S PROPOSED RULE ON EPHEDRINE ALKALOIDS, GAO/HEHS/GGD-99-90 (1999).

(18.) See Stewart, supra note 13.

(19.) See, e.g., Stephen Barrett, The Herbal Minefield (visited Aug. 15, 1999), http://www.quackwatch.com/01QuackeryRelatedTopics/herbs; FDA Web site, supra note 16; Center for Food Safety and Applied Nutrition, http://vm.cfsan.fda.gov/list.html (part of the FDA, contains the Office for Special Nutritionals); Office of Dietary Supplements, http://dietarysupplements.info.nih.gov (part of the National Institutes of Health, established by the DSHEA); VARRO E. TYLER, THE HONEST HERBAL: A SENSIBLE GUIDE TO THE USE OF HERBS AND RELATED REMEDIES (3d ed. 1997) (balanced approach by recognized authority).

(20.) PDR FOR HERBAL MEDICINES (1998).

(21.) See Miller, supra note 3, and its citations.

(22.) Getting Straight Facts on Herbs, TUFTS U. HEALTH & NUTRITION NEWSL., May 1998, reprinted in 5 COLLEGIUM AESCULAPIUM NEWSL., Sept. 1998, at 3.

(23.) See Kurzweil, supra note 10.

(24.) Ephedra is the genus name of 40 different species, each with differing amounts of ephedrine alkaloids. The raw herb sold to ephedra producers varies greatly in the amount and type of alkaloids. Vitamin Research Products, Inc., Ephedra on the Ropes (visited Sept. 7, 1999), http://www.vrp.com/Library/epdera.htm.

(25.) Schlendorf v. Alternative Health Research, Inc., No. 3:97-CV-104-RV (SMN) (N.D. Fla. settled May 20,1998); see also Richard D. Hailey, Discovery in the Over-the-Counter Drug Case, 1999 ATLA ANNUAL CONVENTION PAPERS 207.

(26.) See In re Showa Denko K.K., MDL No. 865 (D.S.C. 1994). For more details on this mass tort, see PAUL D. RHEINGOLD, MASS TORT LITIGATION, ch. 4 (1996).

(27.) See Jody L. Aaron, Death Over-the-Counter: Dangers of Ephedrine, TRIAL, Dec. 1997, at 61. The author refers to a then-pending class action, Nanney v. General Nutrition Corp., No. 95-0160 CIV-KEHOE (S.D. Fla. filed Jan. 26, 1995).

(28.) See, e.g., Richard M. Eldridge & Michael F. Smith, Baker v. Arbor Drugs, Inc.: Pharmacists Beware of Voluntarily Assuming the Duty to Protect Against Harmful Drug Interactions, 14 J. CONTEMP. HEALTH L. & POL'Y 41 (1997); Jill Casson Owen, The Pharmacist's Duty to Warn: Lasley v. Shrake's Country Club Pharmacy, 37 ARIZ. L. REV. 677 (1995); Angelo J. Patane, Comment, OBRA '90 and Developing Case Law: Will the New Revolution Live up to Its Underlying Goals? 1 J. PHARMACY & L. 177 (1992).

RELATED ARTICLE: Study supplements before you take the case

Attorneys must undertake specialized investigations before committing time and resources to litigation involving herbal supplements.

Causation is the first issue to address. Did the product ingested cause harm? This issue is particularly perplexing with herbal products. Key ingredients may be outlined on the product package, but the lawyer must ascertain if those ingredients are actually in the product. Other ingredients may be contained as contaminants or in conjunction with the identified ingredients.

The quantity of the ingredients is also important. Some ingredients are harmless in small quantities or when ingested alone, but if taken with other substances or in large quantities, they may pose substantial dangers. Herbal products contain ingredients grown under a variety of circumstances, and alkaloids and metabolites of herbal ingredients can vary dramatically from batch to batch. The precise quantity of ingredients can be difficult to ascertain, especially since manufacturers are not required to standardize product contents.

A reputable laboratory can evaluate product ingredients and quantity. Obtaining other samples from the same batch of the product will help the analysis, and even samples from a different batch (if the original batch is no longer available) may be useful.

The attorney or client should immediately submit to the FDA an adverse event report that identifies the product and the problem associated with its use. The agency can seize records, order the manufacturer to provide samples from the same batch if available, and require disclosure of product information that may not be publicly revealed.

If the FDA does not take prompt action, the attorney should directly notify the manufacturer about the problem and ask that it preserve the batch, furnish product information, and cooperate fully with the investigation.

The medical examiner or a pathologist or other physician can help make the connection between a product and injury or death. The simplest causation link is ingredients widely known to be associated with the symptoms experienced. For example, ma huang, or ephedra, is associated with increases in blood pressure. The drug ephedrine has been linked to arrhythmias, hypertensive crises, stroke, and death. Ephedra is sufficiently similar to synthetic ephedrine that attorneys can use reports from peer-reviewed medical literature regarding synthetic ephedrine's effects to connect ephedra and injury.

Missing link

If no link has been made between a product and an injury, the attorney must help the physician or pathologist make the connection. The attorney should provide information about product ingredients and quantities; documented effects, including adverse event reports investigated by the FDA or state or local health departments; and a history of what happened to the client.

The causation expert may be skeptical about linking an herbal product to a devastating injury. Facts will substantiate the allegation. The degree of irresponsibility exercised by the manufacturer or marketer may highlight dangerous practices related to the sale of the product. Shocking representations about the product's use, effectiveness, and safety should be pointed out, as well as the absence of any warnings about potential effects.

The attorney must also be prepared for Frye and Daubert challenges.(1) The Dietary Supplement Health and Education Act of 1994 exempted manufacturers from testing herbal products and created perhaps the biggest hurdle to civil litigation. Because premarket approval is not required and product claims are not substantiated, I know of no data on herbal products in peer-reviewed medical journals. So, it is virtually impossible to meet the traditional criteria under Daubert. Ironically, the lack of care in the manufacture and marketing of herbal products gives manufacturers a strong defense. By failing to test and document the effects of products, manufacturers can say there is no scientific proof that their products cause harm.

Attorneys must exhaust all sources to learn about the offending herb. Pharmacognosy is the study and research of natural products. Some publications, including Lawrence Review of Natural Products,(2) outline uses, contraindications, and warnings for natural products, and the German Monographs(3) represent years of data assessment and compilation on natural products.

While mainstream medicine offers scant information on herbal products, there is a developing body of information by herbalists, pharmacognosy practitioners, teachers, and health-food industry organizations. And as physicians become aware of potential interactions between prescribed medications and natural products, greater attention is being given in medical literature to herbal products.

Notes

(1.) Frye v. United States, 293 F. 1013 (D.C. Cir. 1923), superseded by statute as stated in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 529 (1993).

(2.) See, e.g., ARNICA, THE REVIEW OF NATURAL PRODUCTS (1998).

(3.) THE COMPLETE GERMAN COMMISSION E MONOGRAPHS: THERAPEUTIC GUIDE TO HERBAL MEDICINES (M. Blumenthal ed., 1998).

Virginia M. Buchanan is a partner at Levin, Middlebrook et al. in Pensacola, Florida.

Paul D. Rheingold is a partner with Rheingold, Valet, Rheingold & Shkolnik in New York City.