HERBAL DRUGS

OFFICIAL NAMES: Botanicals, nutraceuticals, phytopharmaceuticals, dietary supplements, natural supplements

STREET NAMES: Ginseng (Panax ginseng), echinacea (Echinacea purpurea), ginkgo (Ginkgo biloba), garlic (Allium sativum), saw palmetto (Serenoa repens), St. John's wort(Hypericum perforatum). St. John's wort is also known as hardhay, amber, goatweed, Klamath weed, and Tipton weed. Garlic supplements are Garlix, Gar-Pure, and Cardiomax.

DRUG CLASSIFICATIONS: Not scheduled, dietary supplements

OVERVIEW

Herbal drugs are made from the roots, stems, leaves, bark, fruit, seeds, or flowers of various plants known or believed to have medicinal properties. Many conventional drugs are also derived from plants. In fact, the word "drug" comes from the French word drogue, meaning "dried herb."

Herbal and conventional drugs differ significantly, however. When a conventional drug is derived from a plant, this drug is a purified form of the specific substance in the plant that is proven to have a beneficial medical effect. This substance, called the active ingredient, is delivered to the patient in a precise amount, or dose. Herbal drugs, in contrast, are made up of all the other substances and chemicals in the plant, in addition to any active ingredient they might contain. Sometimes, manufacturers of an herbal drug aren't sure which substance in the plant is the active ingredient, or how much active ingredient their herbal product delivers. Even when the active ingredient is known, the amount of it can vary widely—as much as 10,000-fold—between products made by different manufacturers.

Because herbal drugs are not regulated as drugs by the FDA, they don't have to undergo the rigorous testing that conventional drugs must undergo before they are marketed. The manufacturers of conventional drugs must prove the safety and efficacy of their products to the FDA before the FDA approves their use. This proof comes in the form of extensive scientific studies of the drug in animals and in people. With herbal drugs, the situation is reversed: Because herbals are classified as foods, the FDA bears the burden of having to prove an herbal product is unsafe before the agency can take it off the market or restrict its use.

The controversy over herbals

The increasing use of herbal drugs in the United States and Europe during the last decades of the twentieth century has generated considerable controversy. Opponents of herbal drugs point to the lack of conclusive scientific evidence that these substances are safe and effective. They warn about the lack of standards in manufacturing that have led to toxic and sometimes fatal side effects and adverse reactions, and they call for more strict regulation of their sale and use. Proponents argue that herbal remedies have been around for thousands of years and so have stood the test of time, and they point to the growing number of scientific studies that seem to indicate that some herbal medicines work. Both sides call for more research to determine which herbal drugs are actually effective and which may be ineffective or even dangerous.

A brief history of herbal medicines

People have long recognized the healing properties of certain plants. Herbal drugs have likely been around as long as humans have. Medicinal herbs were found on the body of an "ice man" frozen in the Swiss Alps for more than 5,000 years. Scientists think the man used these herbs to treat an intestinal disorder.

Many herbal medicines have an ancient history. The ginkgo tree has long been cultivated for medical use in China and Japan, where some of these hardy trees are over 1,000 years old. Chinese herbalists made tea from ginkgo seeds and prescribed the drink for many problems, including memory loss and asthma. In the 1700s, the tree was brought to Europe from China. In the 1950s, the Dr. Willmar Schwabe Company of Germany investigated the properties of the ginkgo leaf for possible medical use, and by 1970, ginkgo became one of the most widely prescribed herbals for dementia and for a type of weakness and pain in the limbs called intermittent claudication. In 1997, the Journal of the American Medical Association (JAMA) published a study indicating ginkgo might be useful in treating Alzheimer's disease, sparking interest in the United States.

Before Europeans arrived in America, echinacea was a popular herbal drug among Native Americans, who used it to treat respiratory infections, inflammation of the eyes, toothache, and snakebite. European colonists quickly adopted the herb. In the nineteenth century, European Americans used echinacea as a "blood purifier," believing that it cleared the blood of disease-causing toxins. Europeans used echinacea to treat diseases such as eczema, veneral diseases, lymphangitis (swelling of the lymph vessels), and sepsis (infection of the blood with microorganisms).

Many of the herbal drugs used in the United Sates and Europe are derived from traditional Chinese medicine and Ayurvedic medicine in India. These traditions are thousands of years old, and they rely heavily on plant-based prescriptions to treat various illnesses. Many other herbal drugs are folk remedies from other cultures. Historians of medicine note that every culture has its own tradition of folk medicine: treatments or cures widely believed to be effective, based on information gathered from trial and error on the curative properties of plants and passed down through generations.

Before the advent of modern and synthetic drugs in the nineteenth century, the United States had its own folk medicine tradition. In colonial times, people often relied on homemade botanical remedies based on the folk traditions of their original countries. People also learned about the healing properties of local plants from Native Americans.

As more Europeans came to the Americas and settlements grew into cities, some herbal remedies transformed into "patent medicines," which people could buy at the local store or from traveling salesmen. Packaged in fancy bottles and laced with generous amounts of alcohol, these medicines were of doubtful value, although their labels claimed they could cure everything from the common cold to cancer. One manufacturer of such medicines was H. C. F. Meyer, who in the late 1800s sold combinations of echinacea and other herbs. His outlandish, exaggerated, and poorly written labels helped define the "snake oil salesman" as an American icon.

From herbs to conventional drugs

In the 1800s, doctors, pharmacists, and scientists began to examine herbal remedies more closely. They began to identify the active ingredients in medicinal plants and to isolate and purify those substances. For example, the French pharmacist H. Leroux purified the drug salicin, the precursor of aspirin, from the bark of the willow tree in 1829.

The 1800s saw the transformation of many herbal remedies into conventional drugs. The story about how one herb, foxglove (Digitalis purpurea), was transformed into the modern-day cardiac drug digoxin, provides a good example.

In the 1700s, the condition known as dropsy was a common cause of death. (In the twenty-first century, doctors call dropsy congestive heart failure.) Dropsy occurs when the heart is too weak to keep all of the blood moving through the body. The blood accumulates in blood vessels and eventually seeps into surrounding tissues. Dropsy sufferers begin to swell with the excess fluid, and their arms and legs puff up so that they cannot move. Oftentimes, fluid fills the lung cavities and makes it impossible to breathe. Dropsy victims actually drown in their own bodily fluid.

In England, the folk remedy for dropsy was an herbal decoction, or "soup," made from boiling about 20 different plants, including the herb foxglove. In the late 1700s, the English doctor and botanist William Withering, practicing in Stafford, examined this herbal remedy more closely. He recognized that the folk remedy worked, and he systematically tested each plant ingredient on his dropsy patients until he found the one that improved heart function—the leaf of the foxglove plant, also known as digitalis leaf.

Although he had discovered the medicinal properties of foxglove, Withering ran into a big problem: dosage. As he began to treat patients with a decoction of foxglove, he found that the boundary between an effective dose and a fatally poisonous one was dangerously slim. One of Withering's first patients recovered after just a few doses. But another of Withering's patients almost died from the effects of foxglove overdose—continuous vomiting and diarrhea. The dosage problem was complicated by the fact that the foxglove plant varied in potency from plant to plant and in different seasons. Withering would have to use three times as many leaves for his decoction in winter than in summer, when the plant bloomed.

In 1775, Withering began 10 years of experiments with foxglove. He gave dropsy patients small doses of the herb to start with, then gradually increased the dosage until the vomiting and diarrhea started. When that happened, he decreased the dose a little until the side effects disappeared but the beneficial effect on the heart remained. In this way, he was able to roughly determine the correct dosage. In 1785, he published a famous book on the properties of the foxglove plant, An Account of the Foxglove and Some of Its Medical Uses. The medical community recognized foxglove as a remedy for congestive heart failure until well into the twentieth century.

However, in the 1800s efforts were under way to purify the active ingredients from herbs and do away with the plant altogether. In 1804, the German pharmacist F.W. Serturner discovered how to isolate the chemical morphine from the poppy plant (Papaver somniferum). In 1870, the French researcher C.A. Natvelle used a similar process to purify a substance he called digitalin from the foxglove leaf. This purified substance became the conventional cardiac drugs digoxin and digitoxin.

In the late 1800s and early 1900s, advances in chemistry allowed scientists to further modify the drugs derived from plants to reduce their side effects. Chemists were also able to synthesize in the laboratory entirely new drugs with new beneficial properties. Eventually, it became cheaper and easier to synthesize the substances once derived from plants, rather than extract them from herbs themselves.

As modern, scientific medicine offered a growing number of effective drugs, interest in herbal remedies declined. The first edition of the United States Pharmacopoeia, a drug compendium published in 1820, listed about 200 plants recognized as drugs. These included hops (Humulus lupulus), licorice (Glycyrrhiza glabra), peppermint (Mentha piperita), senna (Cassia senna), and valerian root (Valeriana officinalis). But by 1936, the Pharmacopoeia listed on only 79 herbal drugs.

In the 1960s, however, a popular interest in alternative and complementary medicine sprang up in the United States and Europe. This growing interest in alternative medicine, which includes use of herbal drugs, has continued into the twenty-first century. Historians, public health experts, and cultural commentators are not sure why alternative medicine has become so popular, but they point to several factors that likely influenced this cultural shift.

First, the cost of health care has been rising, and people have grown dissatisfied with managed care, which has resulted in people spending less time with their doctors. Second, people have been concerned about the safety of synthetic drugs, especially after the tragedy, beginning in Europe, of birth defects caused by the drug thalidomide. Third, many people have conditions for which conventional medicine has produced no satisfactory cure, such as certain cancers, back pain, and arthritis. Disillusioned with scientific medicine and desperate for relief, these people have turned to alternative therapies such as herbal drugs. Finally, the cultural emphasis on health and wellness, self-reliance, and a renewed focus on all things "natural," has probably led to the increased use of herbal drugs. Kenneth Shine, president of the U.S. Institute of Medicine, has commented that the easy availability of information about herbal drugs on the Internet probably has contributed their increased use.

CHEMICAL/ORGANIC COMPOSITION

The chemical composition of herbal drugs is highly complex and uncertain, especially when compared with conventional drugs. Herbal drugs contain all the chemicals inherent in the plant. Even when the active ingredient in an herbal product is known (or suspected), it is difficult for manufacturers to standardize how much active ingredient their product contains. The potency of herbal drugs is affected by growing conditions, storage, handling, and the manufacturing process used. For example, one manufacturer might grind plants up and put them into pill form, while another might prepare an extract from the plant. The consumer protection-focused magazine Consumer Reports examined the composition of herbals and found that the potency of products based on the same plant varied as much as 10,000 fold.

Herbal products do not always contain the plant they are supposed to contain. In an apparent case of mistaken identity, the Chinese herbal slimming aid "Fangji" was replaced by "Guang fangji" and distributed in Germany and France. The highly toxic Guang fangji caused several cases of a kidney disease known as fibrosing interstitial nephritis. Producers of herbals have also cut costs by padding their product with related but cheaper plants. Because of the high cost of pure ginseng, some products labeled as ginseng are supplemented with mandrake or snakeroot.

Herbal drugs may contain additives not listed on the label, and these additives are sometimes the source of the "herbal" medicine's effect. Investigations by Consumer Reports and others have shown herbal products to contain aspirin, caffeine, steroids, non-steroidal anti-inflammatory drugs, antibiotics, sedatives, and even narcotics.

Finally, herbal products imported from China may be contaminated with pesticides or with heavy metals added during the manufacturing process. Contaminated Chinese herbals have led to cases of arsenic, lead, mercury, thallium, and cadmium poisoning. Similarly, investigations of traditional Indian Ayurvedic remedies have shown them to sometimes contain dangerous levels of lead, zinc, mercury, arsenic, aluminum, and tin.

Flavonoids: an active ingredient in many herbals

Many medicinal plants contain chemical compounds called flavonoids. Some evidence suggests that flavonoids, also called bioflavonoids, can have beneficial effects on the body. Flavonoids may be able to help ward off bacteria and viruses and reduce inflammation. They may also be antioxidants, which are molecules that clear the body of harmful chemicals called oxygen free radicals. (Oxygen free radicals are highly reactive molecules that damage cells and have been associated with diseases such as cancer, diabetes, and cardiovascular disease.)

Flavonoids concentrate in the seeds, bark, flowers, or fruit of most plants. The herbal remedy green tea (Camellia sinensis), which is used for stomach disorders, contains about 30% flavonoids by weight. Apples and onions, which are listed in the Physicians' Desk Reference for Herbal Medicines (PDR-HM), also contain high amounts of flavonoids.

Flavonoids are divided into many classes and subclasses, each with a slightly different chemical structure and function. Classes of flavonoids include flavanols, flavanones, catechins, anthocyanins, and isoflavones.

Subclasses of flavonoids include genistein, found in soy, and quercetin, found in onions.

INGESTION METHODS

Herbal drugs are taken in a variety of ways. A person looking for ginseng in a health foods store would find ginseng tablets, ginseng capsules, a liquid ginseng extract, dried ginseng root, ginseng gum, and possibly even ginseng cigarettes. Another popular way to take herbal drugs is to make a tea from the dried leaves, roots, or flowers of the plant. Many herbals come in an ointment form, which people apply topically (to the skin) to treat wounds, burns, or skin conditions such as eczema. Following are come common ways herbal medicines are prepared and taken:

A decoction is a tea made from boiling the bark, roots, or other woody parts of the plant in water.

An infusion is a tea made by pouring hot water over the dried leaves, flowers, or fruit of the plant and allowing it to steep. The water is usually boiling, but some infusions use cold water.

A tincture is an extract of the plant made by soaking herbs in glycerine, alcohol, or vinegar for several weeks. The liquid is strained from the plant and can be used therapeutically by adding it to hot water or other beverages. Tinctures can also be taken by the spoonful like other medicines.

A liniment is an extract of an herb added to either alcohol or vinegar and applied to the skin.

A poultice is a soft, moist mass of plant material, often crushed or bruised, which has been wrapped in a fine woven cloth. People apply poultices to burns, wounds, or other skin damage or disease.

THERAPEUTIC USE

The potential therapeutic effects of herbal drugs have not been extensively tested or conclusively proven. However, scientific study of herbals is under way in the United States and abroad, and many herbs may well prove to be useful. The results of initial studies on many herbals, such as saw palmetto and St. John's wort, are promising.

Because herbal medicines are not classified as drugs by the FDA, the manufacturers of herbals cannot make claims that their product is effective at treating any disease or disorder. They can, however, make more general health claims. For example, companies that sell St. John's wort cannot say their product is useful for treating depression or anxiety, but they can say St. John's wort "helps support a healthy emotional balance" or "helps maintain a positive attitude."

Despite the lack of conclusive evidence on their effectiveness, herbal drugs are widely believed to be useful in treating a variety of conditions, both common and unusual, and mild and serious. Common conditions for which people take herbal drugs include colds and flu, muscular aches and pains, acne, indigestion, constipation, coughs, corns, menstrual cramps, dandruff, diarrhea, fatigue, flatulence, frostbite, warts, hair loss, headaches, heartburn, insect bites, lice, motion sickness, nausea, insomnia, dizziness, and warts. (The PDR-HM lists 25 herbal medicines used to relieve flatulence.)

More serious conditions for which people take herbal drugs include depression, irregular heartbeat and other heart problems, arthritis, arteriosclerosis (hardening of the arteries), asthma, high blood pressure, various cancers, diabetes, epilepsy, gallstones, sexually transmitted diseases, hepatitis, jaundice, malaria, measles, obesity, tetanus, tuberculosis, and ulcers.

As popular interest in herbal medicines grows, scientists have been conducting more clinical trials (studies in people) to evaluate herbals' effectiveness at treating particular disorders. One source of reliable, scientific knowledge on herbal drugs is the reports from the German government's herbal watchdog agency, the so called "Commission E." After reviewing the scientific literature on more than 300 herbals, this commission approved more than 200 and disapproved about 100 for use in Germany. Building upon the work of Commission E, the PDR-HM, published in the United States, lists about 600 herbal medicines, and gives an evaluation of the usefulness of each. Another good source is the Clinical Evaluation of Medicinal Herbs and Other Therapeutic Natural Products, also published in the United States. This book evaluates and reports on the clinical trials performed on a wide variety of herbs.

Following is a list of popular herbal drugs in the United States, the therapeutic use or uses for which people take them, and what scientists have learned so far about their effectiveness:

• Echinacea. The several varieties of this plant, also called the purple coneflower, are used to strengthen the body's immune system and for both prevention and treatment of colds and flu. Sixteen clinical trials involving over 3,000 patients have produced mixed results. In some of the studies, echinacea reduced the severity and duration of colds and flu. However, the evidence that this herb can actually prevent colds and flu is weak at best.
• Garlic. Fresh and dried garlic are used to lower cholesterol and to treat the common cold, coughs, bronchitis, fever, and inflammation of the mouth. Garlic appears to be effective for these uses. Twenty-five clinical trials involving more than 1,000 patients

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  have tested garlic's cholesterol-lowering properties. Although these studies produced mixed results, they indicate overall that garlic can reduce cholesterol by about 10%. Other uses for which garlic has not been proven effective include treatment of menstrual pain and diabetes.
• Ginkgo. The leaves and seeds of this plant, native to China, Japan, and Korea, are used to improve agerelated loss of memory, including the dementia associated with Alzheimer's disease, and to relieve ringing of the ears and a type of pain and weakness in the limbs called intermittent claudication. More than 40 studies involving more than 1,000 patients show that ginkgo has a modest effect on dementia and intermittent claudication, but does not seem to help with memory loss or ringing of the ears.
• Ginseng. The dried roots of this plant, which is native to China, are believed to increase stamina and concentration. Few well-designed, rigorous studies of ginseng have been conducted, and those that have been done found no evidence for ginseng's effectiveness.
• Saw palmetto. The fruit of this plant, indigenous to the southern coastal regions of the United States, is used to relieve urination problems caused by an enlarged prostate gland. Sixteen short-term clinical trials involving approximately 3,000 men indicate that saw palmetto is effective for this use, although long-term trials need to be done to confirm the herb's effectiveness. The herb improves urine flow, although it does not seem to reduce the size of the prostate. In some European countries, saw palmetto is commonly prescribed for men with an enlarged prostate.
• St. John's wort. The dried buds and flowers of this plant are used to treat mild to moderate depression and anxiety. More than 30 well-designed studies involving thousands of patients show the herb works about as well as conventional antidepressants for treating mild to moderate depression.

USAGE TRENDS

Scope and severity

Estimates of herbal drug use in the United States vary, depending on how the researchers define herbal drugs and what types of questions they ask in their surveys. However, all research indicates that the use of herbal drugs grew substantially during the 1980s and 1990s. Sales of herbal drugs increased by as much as 20% per year during these decades, far outpacing sales of conventional drugs. By most estimates, Americans spend more than $1 billion each year on herbal medicines. A report prepared by the Nutrition Business Journal estimates that Americans spent more than $4 billion on herbal drugs in 2000.

About 14% of the U.S. population uses herbal drugs or other dietary supplements, according to a telephone survey conducted by the Slone Epidemiology Unit of Boston University. The results of this survey, which asked participants if they had taken an herbal remedy during the past week, were published in a 2002 issue of JAMA.

Another survey published in 2000 yielded a much higher figure for herbal drug use. Forty percent of patients at a health maintenance organization (an HMO) took herbal drugs, according to a survey published in the Journal of the American Pharmacists Association. The herbals most frequently used were garlic, aloe, cranberry, and echinacea.

Age, ethnic, and gender trends

According to the Slone survey, middle-aged men and women tend to be the most frequent users of herbal drugs or dietary supplements. However, researchers found that it is mostly young men who take the supplement creatine, which is promoted as a muscle builder. Older men most often took saw palmetto and also the dietary supplement glucosamine, which is believed to combat arthritis. Older women most commonly took ginkgo.

A survey of 272 college students found that almost half, or 48.5%, reported taking an herbal drug within the past year, according to a study published in the Journal of American College Health. Echinacea, ginseng, and St. John's wort were the most popular herbals among these college students, and the study found no significant difference in herbal drug use between males or females, or among students of different ethnic backgrounds.

Elderly Americans take their share of herbal medications, according to a study conducted by the University of Michigan and presented at the 2002 annual meeting of the American Association for Geriatric Psychiatry. This survey of elderly veterans with depression or dementia found that 20% of them were treating themselves with herbal drugs. Of the elderly patients using herbals, 33.3% used ginkgo, 26.7% used St. John's wort, and 20% took other herbs.

Ethnic trends

Because herbal drugs are a relatively new phenomenon, little data exist on differences among ethnic groups in herbal drug use. However, a study published in the Journal of the American Pharmacists Association in 2000 concluded that Hispanics used herbal drugs more often than whites, and that Hispanics and whites preferred different methods of taking herbal drugs. After administering a questionnaire to patients age 65 and older at a senior health center, the study's authors determined that 77% of the Hispanics used herbal remedies, as opposed to 47% of the whites. (The overall usage rate was 61%.) In addition, Hispanics preferred herbal teas, while whites most often took their herbals in a capsule or tablet form.

Herbals around the world

Europeans are even more enthusiastic than Americans are about herbals. Europeans spend three times as much on herbal drugs as Americans do. In Germany, two-thirds of the population uses herbal drugs, according to one poll. Herbal medicines make up about 30% of all drugs sold in German pharmacies, and German physicians routinely prescribe these medicines. Part of the reason for the greater acceptance of herbals in Germany is that the German equivalent of the FDA strictly evaluates and regulates herbal products, so consumers feel more confident about using them.

Worldwide, more than 80% of the population uses herbal and folk remedies. In developing countries where many people do not have access to modern health care, traditional folk medicine is the only option.

MENTAL EFFECTS

Many herbal drugs are believed to reduce anxiety and depression The PDR-HM lists 47 herbals used to manage anxiety disorders. Of these, St. John's wort and kava (Piper methysticum) are popular in the United States, and although they are not proven medicines, preliminary evidence suggests they may be effective.

The active ingredient of St. John's wort is a substance called hyperforin. Like other antidepressants, hyperforin appears to work by helping to restore the proper balance to brain chemistry. In particular, hyperforin helps restore the balance of certain neurotransmitters, or chemical messengers, in the brain. These neurotransmitters include serotonin, norepinephrine, and dopamine.

Kava contains a substance called dihydrokavain, which is a mild sedative and pain reliever. Preliminary research shows that kava reduces nervous anxiety, tension, and agitation, although these effects usually take at least a week, and often a month or more, to set in. Although other anti-anxiety drugs such as benzodiazepines are more effective than kava, the herb does not seem to impair mental functioning or reaction times the way benzodiazepines do.

Some researchers suggest that perhaps the biggest mental effect induced by those herbals that are untested and unproven is the placebo effect: If people believe they are taking an effective medication, their attitude about their illness improves and they feel better, at least initially. In particular, the placebo effect can cause patients to report improvements in subjectively measured symptoms such as pain or depression. That is why many drug studies include a placebo group—patients who receive a dummy pill instead of the drug being tested. That way, researchers can compare the placebo group with the group receiving the drug and determine if the drug in question induces more than the placebo effect.

PHYSIOLOGICAL EFFECTS

Herbal drugs act on the body in a variety of ways. Echinacea may boost the body's immune system and help fight off bacterial and viral infections. Garlic appears to lower levels of cholesterol in the blood. Ginkgo may improve circulation by thinning the blood. The chemical compounds called flavonoids found in many herbal medications may help clear the body of harmful molecules called oxygen free radicals. However, exactly how echinacea, garlic, ginkgo, and other herbal drugs affect the body is still being studied.

Harmful side effects

All drugs, even conventional drugs, may cause toxic side effects in some people, and herbal drugs are no exception. Critics of herbal drugs believe that they carry a greater risk of harmful side effects than conventional drugs do because the lack of manufacturing standards and quality control for herbal drugs leads to uncertainty about their potency. The skeptics cite a long list of documented toxic side effects and even fatalities caused by herbals, and they point to a list of herbal drugs known to cause serious side effects.

Proponents of herbal drugs argue that these medications must be safe because they have been used by countless people for thousands of years. They cite preliminary studies that show that some herbal remedies work as well as conventional drugs and produce fewer side effects. For example, an herbal mixture of fennel, peppermint, and wormwood improved symptoms of abdominal pain more effectively and with fewer side effects than the conventional drug metoclopramide, according to a study published in Phytomedicine. And many studies have shown that St. John's wort seems to be as effective as standard antidepressants for mild to moderate depression while carrying a lower risk of side effects.

Following are some herbals known to cause serious side effects:

• Comfrey (Symphytum officionale). Ointments made from comfrey are used topically for wound and bone healing. Comfrey tea and pills have been prescribed by herbalists to treat gastrointestinal ulcers and diarrhea. However, the FDA advised dietary supplement manufacturers to take comfrey off the market in 2001 because of the gathering evidence that comfrey taken internally causes severe liver toxicity. The FDA also noted the lack of evidence for comfrey's effectiveness. Comfrey should not be used by pregnant women or breastfeeding mothers.
• Ephedra (Ephedra sinica), also called ma huang. This herb contains amphetamine-like substances called ephedrine alkaloids that can powerfully stimulate the heart and central nervous system. Ephedra is most often taken by young and middle-aged adults for weight loss, increased energy, and body building. The FDA has received and investigated hundreds of reports of serious side effects associated with ephedra, including high blood pressure, irregular heart rate, seizures, heart attacks, strokes, and death. People with high blood pressure, heart conditions, and neurologic disorders should not take ephedra. Pregnant woman should also avoid this herb.
• Kava. This herb has been promoted for a variety of uses, including relief of stress, anxiety, insomnia, and premenstrual syndrome. However, in 2001 the FDA wrote a letter to health care professionals advising them that kava had been implicated in 25 cases of severe liver toxicity in Germany and Switzerland. The FDA has also received several reports of serious injuries associated with kava in the United States, including one report of a previously healthy woman who required a liver transplant. Kava should not be used by pregnant women or breastfeeding mothers.
• Licorice (Glycyrrhiza glabra). Herbalists use licorice root and licorice juice to treat gastritis and stomach ulcers. However, licorice can cause significant sodium retention and high blood pressure in people who consume more than 3 grams per day for more than six weeks. Licorice should not be used by pregnant women or by patients with liver diseases such as chronic hepatitis or cirrhosis of the liver.
• Pennyroyal (Mentha pulegium). This widely available herb, drunk as an infusion, is used for digestive disorders, colds, and skin diseases. It is also used to induce abortions. However, pennyroyal is known to be toxic to the liver. One published report documented more than 20 cases of severe toxic reactions caused by this herb, including two fatalities. The PDR-HM recommends against using pennyroyal. Because pennyroyal can cause abortions at high doses, pregnant women especially should not use it.
• Finally, initial studies indicate that the following herbals are likely free of serious side effects: chamomile, garlic, ginkgo, peppermint, sabal (Sabal serrulata), saw palmetto, and St. John's wort.

Long-term health effects

No one knows what the long-term health effects of taking herbal drugs might be. Long-term studies to assess the delayed effects or rare adverse effects of herbals have not been conducted.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

One in six patients taking prescription drugs is also taking one or more herbal drugs, according the Slone survey published in JAMA. The study's authors concluded that this situation creates a high potential for adverse drug-herb interactions. Although most herbals have not been studied for possible interactions with prescription drugs, a few researchers are beginning to explore this potential problem. Following is a list of some herbal drugs commonly used in the United States and what is known about their interaction with conventional drugs.

Cranberry (Vaccinium macrocarpon). Excessive intake of cranberry juice, used to treat urinary tract infections, may reduce the blood levels of certain drugs, including some antidepressants, antipsychotics, and morphine-based painkillers.

Dong quai (Angelica sinensis). One study in rabbits suggests that this herb can enhance the blood-thinning effect of the drug warfarin, although dong quai does not appear to have any blood-thinning ability on its own. (Herbalists believe dong quai relieves menstrual cramps, pre-menstrual syndrome, and many symptoms of menopause.)

Echinacea. Studies have so far found no drug interactions for this herb. In Germany, echinacea is often combined with antibiotics to treat bacterial infections, although no studies have evaluated the safety or effectiveness of this combination.

Garlic. According to a study from the National Institutes of Health, garlic supplements sharply decrease the amount of the anti-HIV drug saquinavir in the body, presumably reducing the drug's effectiveness. In addition, because of garlic's apparent blood-thinning properties, it should be used with caution by patients who are already on blood-thinning drugs such as warfarin. One study indicated that patients taking both warfarin and garlic took longer to stop bleeding.

Ginkgo. Because this herb can inhibit blood platelet activity, it should be used cautiously with blood-thinning drugs such as warfarin, heparin, or even aspirin.

Ginseng. This herb may react with the drug phenelzine, causing headaches, tremors, and maniclike symptoms, according to reports. However, it is possible that the ginseng in these cases may have been contaminated with caffeine. Ginseng also lowers blood concentrations of alcohol and warfarin.

Kava. This anti-anxiety herb may react synergistically with (enhancing the effect of) drugs that affect the central nervous system, such as alcohol, barbiturates, or prescribed anti-anxiety drugs. One patient was hospitalized from a reaction between Xanax and kava extract. Herbalists often recommend combinations of kava and St. John's wort to treat anxiety, but the safety of this combination has not been established.

St. John's wort. Preliminary reports indicate that St. John's wort may interfere with the anti-tumor drugs etoposide (VePesid), teniposide (Vumon), mitoxantrone (Novantrone), and doxorubicin (Adriamycin). This herb also lowers the amount of indinavir, an anti-retroviral drug used to treat HIV/AIDS, in the blood. Because St. John's wort likely reduces the effect of other anti-retroviral drugs as well, people being treated for AIDS should avoid this herb.

Valerian (Valerian officinalis). No drug interactions have been reported, but animal studies suggest that valerian, used as a sedative and sleep aid, might increase the effects of barbiturates such as pentobarbital, hexobarbital, and thiopental.

PERSONAL AND SOCIAL CONSEQUENCES

Doctors and public health advocates repeatedly warn about one negative consequence of using herbal remedies: Patients who use herbs and other alternative treatments are more likely not to take advantage of conventional treatments, and the results of this decision can be disastrous. Many doctors have seen patients with early-stage cancer who decided to treat themselves with herbal drugs rather than undergo conventional cancer treatment such as chemotherapy. When the herbal treatments failed, the patients returned to their doctors, but by that time their cancers had progressed to the stage where they were incurable.

Doctors warn that people who take herbals may also be more likely to continue unhealthy behavior, such as smoking or drinking large amounts of alcohol, with the mistaken belief that their herbal remedies will protect them from the negative consequences.

A person is probably more likely to accidentally overdose on an herbal drug than on a prescribed drug. Because the potency of herbal drugs can vary so widely from manufacturer to manufacturer and even from batch to batch, users never know how much of what substances they are ingesting when they take herbal drugs. Also, many people assume that because herbals are "natural," they are safe. Additionally, they might assume that "if a small amount is good, more must be better." People who continue to feel sick after they have started taking an herbal may end up increasing the dose to dangerous levels.

LEGAL CONSEQUENCES

Legal history

For decades, the FDA and the herbal products industry have engaged in disputes over the proper way to regulate herbal drugs. The FDA has tried to protect consumers from ineffective or unsafe products. The herbal manufacturers, who have grown more influential as their products have increased in popularity, have argued that consumers should have access to information about herbal drugs and be allowed to make their own choices. Following are some of the important laws passed in the United States affecting herbal drugs that highlight the history of this conflict.

The 1938 Federal Food, Drug, and Cosmetic Act mandated that all new drugs, including herbals, be proved safe before they could be sold. This legislation was prompted when a sulfa drug containing an unsafe additive killed more than 100 people in 1937. However, this law said that it was up to the FDA to prove a drug was unsafe. Drug manufacturers did not have to explicitly prove their products were safe.

The Kefauver-Harris Drug Amendments of 1962 shifted the burden of proof to drug manufacturers. For the first time, drug manufacturers had to prove their products were safe and effective before they could be sold. The tragedy in Europe of birth defects caused by the sedative thalidomide spurred U.S. public concern about drug safety and public support for this legislation. (It should be noted that the FDA did not allow thalidomide in the United States because of safety concerns.) In response to this new legislation, many manufacturers of herbal drugs began marketing them as "dietary supplements." This shift allowed them to bypass the new law, but they could no longer make any therapeutic claims about their products.

Congress passed the 1976 Proxmire Amendments to stop the FDA from regulating vitamin and mineral supplements as drugs based on their potency. This legislation also prohibited the FDA from regulating the potency of vitamin and mineral supplements. Although the language of this law did not expressly state that herbal products were also protected from regulation as drugs, it was assumed that herbals were covered as well.

The 1990 Nutrition Labeling and Education Act permitted manufacturers to make some health claims for foods, including dietary supplements, if the claims were approved by the FDA. This law stipulated stringent requirements for claims made on behalf of herbal and dietary supplements. The law also required standardized nutrition labels for all packaged foods.

Federal guidelines, regulations, and penalties

The 1994 Dietary Supplement Health and Education Act expressly defines a dietary supplement as a vitamin, a mineral, an herb or other botanical, an amino acid, or any other "dietary substance." This law prohibits claims that herbs can treat diseases or disorders, but it allows more general health claims about the effect of herbs on the "structure or function" of the body or about the "well-being" they induce. Under this law, the FDA bears the burden of having to prove an herbal is unsafe before restricting its use. This law also established the Office of Dietary Supplements within the National Institutes of Health to promote and compile research on dietary supplements.

The poison squad of 1903

To determine the safety of additives and preservatives in foods and medicines, the U.S. government established a "poison squad" in 1903. This group of young men volunteered to eat foods treated with chemicals such as borax, formaldehyde, and benzoic acid. The principles of the federal laws that arose from this experiment still govern herbal dietary supplements in 2002.

Although establishing the "poison squad" might seem a drastic measure, at the time the U.S. food and drug industry operated virtually without control. Although many manufacturers provided wholesome products, many others used chemical preservatives and toxic coloring agents in foods, and did so with very little regulation or oversight. The government desperately needed knowledge about these additives in order to properly regulate them.

In addition, the purveyors of thousands of patent medicines—containing drugs such as opium, morphine, heroin, and cocaine—sold them without restriction. The makers of these medicines, who regularly made false claims about their therapeutic value, did not even list ingredients or warnings on the labels.

The poison squad was established by Dr. Harvey W. Wiley, head of the U.S. Bureau of Chemistry, the precursor to the FDA. Wiley campaigned for more stringent food and drug laws, sharing his findings with the public through speaking at women's clubs and civic and business organizations.

Patent medicine firms and whiskey distilleries opposed Wiley's campaign, believing new federal regulations would put them out of business. But Wiley's efforts were instrumental in influencing Congress to pass the Food and Drug Act of 1906, which prohibited interstate commerce in misbranded or adulterated foods and drugs. In 1912, Congress passed the Sherley Amendment, which prohibited manufacturers from making fraudulent therapeutic claims when labeling their medicines.

See also Ephedra

RESOURCES

Books

Bratman, Steven, and David J. Kroll. Clinical Evaluation of Medicinal Herbs and Other Therapeutic Natural Products. Roseville, CA: Prima Publishing, 1999.

Ernst, Edzard, ed. Herbal Medicine: A Concise Overview for Professionals. Oxford: Butterworth-Heinemann, 2000.

Fleming, Thomas, ed. Physicians' Desk Reference for Herbal Medicines. Montvale, NJ: Medical Economics Company, 1998.

Klein, Siegrid, and Chance Riggins. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston: Integrative Medicine Communications, 1998.

Miller, Lucinda G., and Wallace J. Murray, eds. Herbal Medicinals: A Clinician's Guide. Binghampton, NY: Pharmaceutical Products Press, 1998.

Periodicals

Dodes, Rachel. "Alternative Medicine from an Ethnobiological Perspective." For Health Priorities 11 no. 3 (1999).

Ernst, Edzard. "Harmless Herbs? A Review of the Recent Literature." The American Journal of Medicine 104 (February 1998): 170-178.

Goldman, Peter. "Herbal Medicines Today and the Roots of Modern Pharmacology." Annals of Internal Medicine 135 no. 8 (October 2000): 594-600.

Hatcher, Tiffani. "The Proverbial Herb." American Journal of Nursing 101 no. 2 (February 2001).

Mitka, Mike. "FDA Never Promised an Herb Garden-But Sellers and Buyers Eager to See One Grow." Journal of the American Medical Association 280 no. 18 (November 11, 1998).

Shine, Kenneth I. "A Critique on Complementary and Alternative Medicine." The Journal of Alternative and Complementary Medicine 7 supplement 1 (2001): S-145-S-152.

Winslow, Lisa Corbin, and David J. Kroll. "Herbs as Medicines." Archives of Internal Medicine 158 no. 20 (November 9, 1998): 2192-2199.

Organizations

American Botanical Council, P.O. Box 144345, Austin, TX, USA, 78714-4345, (512) 926-4900, <http://www.herbalgram.org>.

Food and Drug Administration, Center for Food Safety and Applied Nutrition, 200 C Street, SW, Washington, DC, USA, 20204, (888) 723-3366, <http://www.cfsan.fda.gov>.

National Center for Complementary and Alternative Medicine, National Institutes of Health (NIH), P.O. Box 8218, Silver Spring, MD, USA, 20907-8218, (888) 644-6226, <http://nccam.nih.gov/nccam>.

Office of Dietary Supplements, NIH, 31 Center Drive, Room 1B29, Bethesda, MD, USA, 20892-2086, (301) 435-2920, <http://odp.od.nih.gov/ods>.

Anne Jacobson