Herb and Drug Interactions: An Emerging Issue

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If you ask for Siberian ginseng by name in a Chinese herb shop, you’re likely to be met with bewilderment. Eleutherococcus senticosus is more properly called eleuthero, since botanically, it’s not a gingseng.
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Licorice should be used with caution by those taking prescription diuretics and some heart medications.
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Some studies suggest that St. John’s wort may interfere with a function of the digestive system, raising or lowering the levels of some drugs in the bloodstream.
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American skullcap has long been traditionally used as a gentle sedative. Now researchers have discovered it contains two of the same sedative compounds as its better-researched Chinese relative, Baikal skullcap.

In 2000, the possibility that herbs may interact with prescription drugs caught worldwide attention, despite the fact that such herb-drug interactions are rare. Concern about these interactions increased after wide coverage of two research letters published in the February 12, 2000 issue of The Lancet.

Focus on this issue occurred largely in professional medical literature, as more health-care practitioners prescribe herbs or discuss the use of herbs with their patients. Various surveys have revealed that many consumers who are taking herbs fail to tell their physician or healthcare provider. About 24 percent (more than 44 million) of American consumers use herbs routinely, according to a survey published by Prevention magazine. And 18.4 percent of those surveyed were taking both prescription medications and herbal dietary supplements or multivitamins.

But experts in medicinal herbs caution that herb-drug interactions shouldn’t be taken out of context. Historically, herbs have caused relatively fewer side effects than prescription drugs. For example, clinical trials show that the herb saw palmetto (Serenoa repens) causes fewer problems than conventional prescription drugs for the treatment of benign prostatic hyperplasia. And the German Commission E Monographs, more than 300 therapeutic monographs produced over a sixteen-year period, record only thirty-five potential drug interactions.

Certain herb-drug interactions are well-documented and worth watching for. Below, we summarize some of the recent research. Talk to your physician if combining any of these herbs and pharmaceutical drugs.

St. John’s wort. One report suggested that the use of St. John’s wort (Hypericum perforatum)in AIDS patients taking the protease inhibitor drug indinavir led to lower blood levels of the drug. The authors suggested that St. John’s wort may interfere with a function of the digestive system–called the cytochrome P450 enzyme system –which may in turn produce lower or higher levels of the drugs in the bloodstream. A second letter to the editor in The Lancet attributed a possible drug interaction with cyclosporine in two cases of acute transplant rejection of heart transplant patients to use of the drugs and St. John’s wort. Less publicized scientific reports had previously warned that using St. John’s wort with prescription drugs such as digoxin, theophylline, and other drugs may also produce interactions.

But St. John’s wort is only one of many plant products that may interact with the cytochrome P450 enzyme system. Others include grapefruit juice, broccoli, cabbage, Brussels sprouts, red wine, and tobacco.

Licorice. Licorice root (Glycyrrhiza glabra and related species) should be used cautiously when taking prescription diuretics or digitalis glycosides such as digoxin for heart conditions. The use of licorice with these drugs increases their bioavailability, effectively increasing the dose.

Licorice is also known to cause water retention and hypertension due to sodium retention and potassium loss, according to the Commission E. Its use should be limited to four to six weeks. In addition, people with heart disease, liver disease, or hypertension should avoid licorice. It also should not be used during pregnancy.

Ginkgo and garlic. Ginkgo (Ginkgo biloba) and garlic (Allium sativum) have blood-thinning qualities. Various case reports have been published that suggest these herbs should be used under close supervision in patients taking aspirin or a prescription drug thinner such as warfarin. At least one published study showed that it took twice as long as normal for blood to clot in two patients taking both warfarin and ginkgo.

Kava-kava (Piper methysticum). Some reported interactions fall into the realm of common sense. Kava shouldn’t be combined with central nervous system depressants including alcohol and barbiturates. Using both could lead to an unexpected heightening of the herb’s sedative effects.

If you’re taking antidepressants or psychopharmacological drugs, don’t take kava without medical supervision.

Marshmallow (Althaea officinalis). Marshmallow prep- arations are recognized for their ability to soothe and soften irritated tissue, particularly mucous membranes, and to loosen a cough. The leaves and root both contain mucilagin, the substance that makes the tea “slimy.” Mucilagin coats the stomach and can absorb certain drugs, reducing their bioavailability and action. While no specific drugs are mentioned, the Commission E recommends that health care practitioners note this potential effect.

Psyllium (Plantago spp.). Psyllium seed also contains mucilagin. It has been reported that the simultaneous use of psyllium seeds as a laxative along with lithium salts inhibited the absorption of lithium in the gastrointestinal tract.

As the lines of separation between alternative medicine and modern medicine begin to disappear, the most important factor is that physicians, pharmacists, herbalists, and con- sumers learn to communicate. The future of herbs depends on it.

Siberian ginseng

Fifty years of Russian research and the long history of use in China have catapulted this herb into international prominence. Find out why you might want to call it eleuthero and keep it in your medicine cabinet.

It’s a rainy day, and you’re in San Francisco for a meeting. You have a few hours on your hands, so you decide to go on an adventure to check out herb shops in Chinatown. You wander into an herb shop and ask if they have any Siberian ginseng, which you’ve been taking and which you’re curious to see outside the confines of a gelatin capsule. Siberian ginseng? The clerk doesn’t have a clue what you’re talking about. If you knew to ask for ci-wu-jia, the Chinese name for the herb, you might have had better luck.

The reason the Chinese herb shop clerk may not have heard of Siberian ginseng? In Chinese traditions, the plant isn’t considered a ginseng. In China, “seng” is a term used by root gatherers for medicinal plants with fleshy root stocks used as tonics, so Siberian ginseng (Eleutherococcus senticosus) is not a “seng-producing” plant under this definition.

What’s in a name? When it comes to the word ginseng, the answer is money. Call a plant a type of ginseng, and you can charge more money for it. When Siberian ginseng, also called eleuthero, was first introduced into the American herb market, it was sold under the name Siberian ginseng. Some consider the name choice a marketing stratagem.

But don’t dismiss eleuthero because of a mere misnomer. Fifty years of research and the long history of use show that eleuthero helps the body resist stress and fight off infection–all without significant side effects.

At least fourteen components, collectively called eleutherosides, have been identified from eleuthero. Many of these chemicals are relatively common and found in other plants. One, called eleutheroside E, may be important for stimulant and antistress effects.

In Traditional Chinese Medicine, the bark of eleuthero’s root has been used for centuries as a preventive medicine and general tonic. It’s used for benefiting qi (vital energy), treating deficiency of “yang” in the spleen and kidney, and normalizing body functions. It has also been used as a folk remedy for bronchitis, heart ailments, and rheumatism as well as to restore vigor, improve general health, restore memory, promote good appetite, and increase longevity.

The Russian search for adaptogens

Despite this extensive traditional use, it was not Chinese herbalists who made eleuthero famous. Rather, Soviet researchers in far eastern Russian Siberia brought the herb into the limelight in the early 1960s, following a search for low-priced ginseng substitutes among their native plants.

In 1947, Russian scientist I. I. Brekhman coined the term “adaptogen” to describe substances claimed to increase someone’s resistance of adverse influences. The term was soon applied to eleuthero, which, like true ginseng, was traditionally known as a tonic.

The term adaptogen has a strict, three-part definition, which eleuthero fits:

1. It should be non-toxic, and clinical trials and extensive animal testing generally confirm that eleuthero extract is safe.

2. An adaptogen must be non-specific in its action, and studies on eleuthero show that it improves human performance under a wide-range of stressful conditions.

3. An adaptogen must have a normalizing action, irrespective of current health. Numerous reports, primarily in the Russian literature, identify the herbs ability to modulate or inhibit various disease conditions in a nonspecific manner.

The vast majority of studies on the plant were conducted in Russia using a 33 percent ethanol root extract, a form not presently available in the United States. Positive results with initial studies in Russia showed that the extract produced increased stamina, performance, endurance, reflexes, and concentration. This success prompted a flurry of studies. In 1962 the Health Ministry of the Soviet Union accepted the extract as an official medicine. Eleuthero became the national tonic.

Intensive studies

The clinical studies published by the Soviets from 1960 to 1980 involved both healthy and sick people. Individual studies generally tested only a handful of people at one time, but combined, the research involved more than 2,100 subjects. Study participants ranged from 19 to 72 years old and were generally described as normal or healthy. They were often employed in stressful jobs.

These studies used the extract developed by Brekhman. Doses ranged from 2 to 16 ml, taken one to three times a day for up to 60 consecutive days, followed by a two- to three-week break.

The studies primarily measured the subjects’ adaptogenic response under adverse conditions, including high heat, noise, motion, work-load increase, and exercise. Studies also measured the effects on hearing under conditions of increased auditory disturbances, as well as measuring the effect of the extract on mental alertness, work output, and quality of work. Results were generally positive in these wide-ranging studies, with no reports of significant side effects.

The largest study, published in 1977, included 1,000 adult men and women in Siberia, where the average daily temperature was below freezing. Participants were factory workers involved in metallurgical work or mining. At five intervals throughout the year, they took 4 ml of the extract per day for 30 days. The study reported improved subjective effects (with no elaboration of what they were), a 40 percent reduction in lost work days, and a 50 percent reduction in general illness.

Widespread use and questions

The research convinced the Soviet Health Ministry of the eleutheros value. By 1976, an estimated 3 million Soviet citizens used the extract regularly. The outstanding performance of Soviet athletes at the 1980 Olympics was attributed to their use of eleuthero, and widespread use in Western countries followed.

Some researchers questioned the validity of the Russian studies because they often contained incomplete data, lacked adequate controls, and were not double-blind. Nevertheless, the sheer volume of the data has convinced many, including the German government, of the herb’s potential value. Currently the German government allows eleuthero to be used as a tonic for invigoration and fortification during times of fatigue and debility, as well as for declining work capacity and concentration.

Recent research: immune boosting

In addition to its tonic effect, eleuthero is also considered an immunostimulant like echinacea. Head-to-head in pharmacological tests, eleuthero appears to be as useful or stronger than echinacea as an immuno-stimulating agent.

In fact, some scientists have asserted that this is the best-documented pharmacological effect in terms of quality of scientific research.

A recently published clinical study provides more evidence of immunostimulant effects. Researchers at the Pomeranian University School of Medicine in Poland studied the influence of an eleuthero product on cellular defense mechanisms, blood lipids, and physical performance in 50 volunteers of both genders. One group of 35 individuals received 25 drops of eleuthero extract three times daily. The other group of 15 volunteers received 40 drops of Echinacea purpurea three times daily. At the end of the test period, a significant reduction in total cholesterol, LDL cholesterol, free fatty acids, triglyceride levels, and glucose were observed in the eleuthero group, but not in the echinacea group. Measures of cellular immunity led the researchers to suggest that eleuthero helps susceptibility to chronic infections caused by environmental factors.

Some cautions and mistaken identity

In the United States, some batches of eleuthero have been adulterated by Periploca sepium, the root of a Chinese vine in the milkweed family. The mixup may have happened because the two plants have similar Chinese names. It’s alarming, however, given the fact that P. sepium contains cardiac glycosides and has recently been implicated in causing fetal complications, including an androgenic effect resulting in abnormal development of hair.

P. sepium is also suspected in a case where an eleuthero product interacted with digoxin treatment in a heart patient, effectively doubling the dose of the heart medication. These cases highlight the need for proper botanical identification of eleuthero materials.

One Russian study also suggested that patients with high blood pressure should avoid eleuthero. However, no further details were included. This warning has been repeated in the literature and is also included in the German government’s official regulatory monograph on eleuthero, where use is contraindicated in cases of high blood pressure.


Sedative compounds found in American skullcap

Two research groups concurrently report finding sedative compounds in American skullcap (Scutellaria lateriflora). The compounds compare with the active compounds in the herb’s better-researched Chinese relative, Baikal skullcap (S. baicalensis). This begins to provide scientific proof for its traditional use as a mild sedative.

One study found that, like its Asian counterpart, American skullcap contained the flavones baicalein and baicalin, which have been associated with the sedative and nerve-tonic effects of the Asian species. The study was conducted by pharmacognosist Stefan Gafner and researchers at the University of Ottawa.

The second study reported that the main constituent of the herb was baicalin, not scutellarin, as was previous reported in the literature. The study was conducted by researchers at Mediherb in Worwick Australia and the Australian Phytochemistry Research Institute.

Skullcap is a member of the mint family that grows in rich woods and moist soils occurring throughout eastern North America, with a range extending into the Pacific Northwest. In American herbal traditions, it is known as a nerve tonic and sedative for relieving anxiety, neuralgia, and insomnia. Few studies have been done on American skullcap, but one of its reported compounds, scutellarin, has been shown to have sedative and antispasmodic properties.

Baikal skullcap (S. baicalensis) is the root of a commonly used traditional Chinese herb called huang-qin. Native to northeast China and adjacent Russia, it has been used as a Chinese herbal medicine for more than 2,000 years in prescriptions for high blood pressure, hypertension, insomnia, headache, intestinal inflammation, and other conditions. Until now, almost all research on skullcap has been conducted on the Chinese species. (1)

Plantain review finds significant value

A major review of several hundred scientific papers on plantain confirms many traditional uses of the herb.

The review attributes several healing qualities to plantain, including antibacterial, antifungal, anti-inflammatory, pain-relieving, antioxidant, anti-ulcer, immunostimulating, diuretic, hypotensive, and hypoglycemic activities. The medicinal compounds include flavonoids, caffeic acid derivatives, polysaccharides, and alcohols.

Researcher Anne Berit Samuelsen of the School of Pharmacy at the University of Oslo in Norway recorded hundreds of folk uses of the plant from around the world along with dozens of chemical compounds reported in the literature. Common English plantain (Plantago major) is a weed found in most American backyards. This wide-ranging Eurasian species, now common wherever Europeans have settled, is a well-known folk remedy used for centuries to treat insect bites and stings, inflammation, and promote wound healing. (2)

Self-heal compounds help allergies, inflammation

Korean researchers have isolated compounds that may be responsible for the traditional uses of self-heal to treat inflammation and allergies.

The researchers isolated four organic acids, including betulinic and ursolic acid, which were found to have a strong inhibitory activity against allergenic tests systems in the lab- oratory. One of the acids was found to be as potent as clinically used anti-allergic drugs.

Ursolic acid was found to be the most important anti-inflammatory compound in the plant. Previous studies on ursolic acid have reported anti-tumor and diuretic activity.

Self-heal (Prunella vulgaris), also called all-heal, is a common weed in the mint family. It’s native to Europe and found throughout North America, mainly around dwellings, though it’s common in fields, meadows, and other wild habitats. Traditionally, the leaf tea was used as a gargle for sore throats and mouth sores and internally for asthma, fevers, and diarrhea. Externally, a wash of the tea or poultice is used for ulcers, wounds, bruises, and sores. In China, a tea made from the flowering plant is considered cooling and is used to treat heat in the liver and aid circulation.

Science confirms that self-heal helps dilate the bronchial tubes and plantain preparations are widely used in Europe to treat bronchitis and bronchial spasms. The herb is approved in Germany for treatment of catarrh of the upper respiratory tract and inflamed mucous membranes of the mouth and throat.

Earlier research suggests that self-heal possesses antibiotic, hypotensive, and antimutagenic qualities. Like several mint family members, it contains high levels of natural antioxidant components.

By Steven Foster


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(1) Gafner, S., et al. “Comparison of different extracts of Scutellaria lateriflora by HPLC.” Abstracts of Plenary Lectures, Workshops, Short Lectures and Posters. Natural Products Research in the New Millennium, September 3-7, 2000, Zurich, Switzerland.

(1) Lehmann, R., et al. “Identification of the major flavonoid from Scutellaria lateriflora.” Abstracts of Plenary Lectures, Workshops, Short Lectures and Posters. Natural Products Research in the New Millennium, September 3-7, 2000, Zurich, Switzerland.

(2) Samulesen, A. B. “The traditional uses, chemical constituents and biological activities of Plantago major–a review.” Journal of Ethnopharmacology 71(2000):1-21.

(3) Ryu, S. Y., et al. “Anti-allergic and anti-inflammatory triterpenes from the herb of Prunella vulgaris.” Planta Medica 66(2000):358-360.

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