User login
Do you know how many of your patients are taking herbal preparations? With the proliferation of herbal products, the number could be greater than you think. Between 1990 and 1997, the US population increased its use of herbal medicines by 380%.1 Total out-of-pocket expenditure for herbal medicines in 1997 was $5.1 billion.1Table 1 lists the 10 best-selling herbal medicines in the US.2
Safety issues related to herbal medicine are complex: possible toxicity of herbal constituents, presence of contaminants or adulterants, and potential interactions between herbs and prescription drugs. The quality of herbal medicines is often suboptimal. One reason for this is that they are not adequately regulated, and many experts are calling for a change in this situation. Cost-evaluations of herbal medicine are not available, so they cannot form the basis for clinical decisions.
This article provides guidelines for prescribing herbal medications appropriately.
TABLE 1
10 best-selling herbal medicines (United States, 2001)
| Rank | Herb | Retail sales |
|---|---|---|
| 1 | Ginkgo biloba | 46 |
| 2 | Echinacea | 40 |
| 3 | Garlic | 35 |
| 4 | Ginseng | 31 |
| 5 | Soy | 28 |
| 6 | Saw palmetto | 25 |
| 7 | St John’s wort | 24 |
| 8 | Valerian | 12 |
| 9 | Cranberry | 10 |
| 10 | Black cohosh | 10 |
| Retail sales are rounded figures in million US dollars. | ||
Efficacy
One of the first things to consider when a patient proposes trying an herbal medicine is efficacy. Data on efficacy of herbal medicines are incomplete, yet some treatments have shown promise. The critical question is, Does the remedy work for the patient’s condition? Clinicians should not prescribe or recommend herbal remedies if that question cannot be answered with a firm Yes.
Medical herbalism (ie, the medicinal use of preparations that contain exclusively plant material) once dominated our pharmacopeia but went into rapid decline when pharmacology established itself as a leading branch of therapeutics. During the last part of the 19th and the early 20th century, herbalism virtually vanished from the therapeutic map of the US and the UK. In contrast, many developing countries never abandoned medical herbalism (Ayurvedic medicine in India, Kampo medicine in Japan, and Chinese herbalism in China). In other countries (such as Germany and France), medical herbalism continued a “low-key” coexistence with modern pharmacology. More recently, herbal medicine has experienced a remarkable comeback.
Herbal medicines usually contain a range of pharmacologically active compounds. In some cases it is not known which of these constituents produces the therapeutic effect. Testing for efficacy in this situation is obviously more complex than with synthetic drugs. One approach is to view the entire herbal extract as the active component. To optimise the reproducibility of efficacy studies, extracts must be sufficiently characterised. This is often achieved by standardizing the amount of a single key constituent of the extract (eg, a pharmacologically active ingredient or, if such an ingredient is not known, a marker suitable substance).
Other than the dilemma of standardization, herbal medicines can be scrutinized in clinical trials in much the same way as are other drugs. Several randomized clinical trials of herbal medicines have been published, and systematic reviews/meta-analyses of these studies have become available (Table 2).3,4 The Cochrane database includes about 30 systematic reviews of herbal medicines, and several authoritative books have recently become available.3-6 The conclusions of systematic reviews are often limited by the paucity and varied methodological quality of the primary studies.3,7 Research funds in this area are generally scarce, not least because plants are not patentable.
Generalizations about efficacy of herbal medicines are not possible; each one must be judged on its own merits. Some herbal products have demonstrated efficacy for certain conditions, while others have not. Most products have not been submitted to extensive clinical testing.3 “Clinicians should not prescribe or recommend herbal remedies without well-established efficacy….”7
TABLE 2
Examples of systematic reviews and meta-analyses of herbal remedies
| Common (Latin) name | Active ingredients | Indications | No. of trials | Avg. methodological quality of primary studies | Efficacy | Main result |
|---|---|---|---|---|---|---|
| Feverfew (Tanacetum parthenium) | Parthenolide | Migraine prevention | 5 | Good | Likely | 3 trials were positive, 2 were negative |
| Garlic (Allium sativum) | Alliin | Hypercholesterolemia | 13 | Good (some excellent) | Certain but effect small | Overall effect is significant but of debateable clinical relevance |
| Ginkgo (Ginkgo biloba) | Ginkgolides, bilobalide | Intermittent claudication | 8 | Good to excellent | Certain | Overall positive result |
| Horse chestnut seed extract (Aesculus hippocastanum) | Triterpene saponins | Chronic venous insufficiency | 8/5* | Good | Likely | Active treatment more effective than placebo and equally effective as reference treatments |
| Peppermint oil (Menta x piperial)† | Menthol | Symptoms of irritable bowel syndrome | 8 | Good | Likely | Positive effect of peppermint oil compared with placebo |
| Sources: Ernst et al 20013; Fugh-Berman 2003.4 | ||||||
| *8 trials vs placebo; 5 trials vs reference treatments. † Am J Gastroenterol 1997; 93:1131–1135. | ||||||
Safety
Consumers are attracted to herbal medicines in part because they equate “natural” with “safe.” Yet some herbal medicines pose serious risks.7
First, the active ingredients in herbal preparations can, of course, cause desirable as well as undesirable effects. Table 3 lists examples of commonly used herbal medicines that have been associated with serious adverse effects.3 Traditional use is no guarantee of safety and no acceptable substitute for data.8
A poignant example is kava (Piper methysticum), an herbal remedy that has been used for centuries apparently without problems. Numerous rigorous clinical trials have shown it to be a powerful anxiolytic medicine.9 Recently it has been associated with several cases of serious liver damage.10 Hence it has been withdrawn from the markets of several European countries, and the FDA has issued warnings about its hepatotoxic potential.
Second, the active ingredients in herbal medicines might interact with prescription drugs. For instance, extracts of St. John’s wort (Hypericum perforatum) act as an enzyme inducer on the cytochrome P450 system and increase the activity of the P-glycoprotein transmembrane transporter mechanism. Both effects lead to a reduction of the plasma level of several conventional drugs.11 Perhaps the most serious consequence could be insufficiently low cyclosporine levels in patients after organ transplantation, which jeopardize the success of this procedure.12
Third, some herbal medicines (particularly Asian herbal mixtures) have repeatedly been shown to be contaminated with heavy metals,13 or to contain misidentified herbal ingredients that turned out to be toxic,14 or to be adulterated with prescription drugs.15
Before prescribing or recommending an herbal medication, clinicians must ensure that it cannot generate undue harm.
TABLE 3
Examples of herbal medicines associated with serious adverse effects
| Common (Latin) name | Indication | Adverse effects (examples) |
|---|---|---|
| Aloe vera (Aloe barbadensis) | Various | Juice may cause intestinal pain and electrolyte loss |
| Feverfew (Tanacetum parthenium) | Migraine prevention | “Post-fever syndrome” after discontinuation (migraine, anxiety, insomnia, muscle stiffness) |
| Hawthorn (Crataegus) | Congestive heart failure | Additive effects with other cardiac glycosides |
| Kava (Piper methysticum) | Anxiety | Toxic liver damage |
| St. John’s wort (Hypericum perforatum) | Depression | Increased clearance of a range of prescribeddrugs |
| Tea tree oil (Malaleuca alternifolia) | Skin problems (external) | Allergic reactions |
| Valerian (Valeriana officinalis) | Insomnia | Morning hangover |
| Without positive data demonstrating safety, herbal medications cannot automatically be considered safe for pregnant or nursing women. | ||
Quality
The quality of an herbal preparation partly determines its efficacy as well as its safety. Herbal dietary supplements are not usually regulated as drugs and have repeatedly been found to vary in quality, sometimes being suboptimal.7,16
In the US, such preparations have to meet the requirements set forth in the Dietary Supplement and Health Education Act (DSHEA) of 1994. Thus they are marketed without approval of their efficacy and safety by the FDA. The DSHEA does not allow medical claims to be made for such products. Structure or functional claims are, however, allowed. If safety concerns of a product arise, the burden of proof lies not with its manufacturer but with the FDA. Many experts find this regulation insufficient to guarantee consumer safety and argue for it to be changed.16 In Europe, new legislation will soon regulate herbal medicines. Essentially the legislation will provide that efficacy be demonstrated on the basis of bibliographic data; safety, too, will be governed as it is with conventional drugs.17
Cost
Clinicians should recommend treatments that save money for patients and the healthcare system. Many herbal medications are relatively inexpensive. However, very few proper economic analyses of herbal medicines exist.18,19 So far, only 1 cost evaluation of an herbal medicine has been published.20 This study of symptomatic treatment of chronic venous insufficiency compared the cost-effectiveness of compression stockings with that of an extract of horse chestnut seeds. Its results implied that the treatments were similarly effective and associated with similar costs.
For the prescribing physician, this means decisions cannot presently be based on conclusive cost-analyses. While waiting for such data to become available, decisions will have to be informed by our knowledge on the efficacy, safety, and quality of herbal medications.
Correspondence
Edzard Ernst, MD, PhD, Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, United Kingdom. E-mail: Edzard.Ernst@pms.ac.uk.
1. Eisenberg DM, David RB, Ettner SL, et al. Trends in alternative medicine use in the United States. JAMA 1998;280:1569-1575.
2. Blumenthal M. Herb sales down in mainstream market, up in natural food stores. Herbal Gram 2002;55:60.-
3. Ernst E, Pittler MH, Stevinson C, White AR. The Desktop Guide to Complementary and Alternative Medicine. Edinburgh: Mosby; 2001.
4. Fugh-Berman A. The 5-minute herb & dietary supplement consult. Philadelphia: Lippincott Williams & Wilkins; 2003.
5. Capasso F, Gaginella TS, Grandolini G, Izzo AA. Phytotherapy: A Quick Reference to Herbal Medicine. Berlin: Springer-Verlag; 2003.
6. Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy. Berlin: Springer-Verlag; 2001.
7. De Smet PAGM. Herbal remedies. N Engl J Med 2002;347:2046-2056.
8. Ernst E, De Smet PAGM, Shaw D, Murray V. Traditional remedies and the “test of time.” Eur J Clin Pharmacol 1998;54:99-100.
9. Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Library 2002.
10. Teschke R, Gaus W, Loew D. Kava extracts: safety and risks including rare hepatotoxicity. Phytomed 2003;10:440-446.
11. Carlo GD, Borrelli F, Ernst E, Izzo AA. St. John’s wort: Prozac from the plant kingdom. TRENDS in Pharmacol Sci 2001;22:292-297.
12. Ernst E. St John’s wort supplements endanger the success of organ transplantation. Arch Surg 2002;137:316-319.
13. Ernst E, Thompson Coon J. Heavy metals in traditional Chinese medicines: a systematic review. Clin Pharmacol Ther 2001;70:497-504.
14. Nortier JL, Muniz Martinez. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 2000;342:1686-1692.
15. Ernst E. Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review. J Int Med 2002;251:107-113.
16. De Angelis CD, Fontanarosa PB. Drugs alias dietary supplements. JAMA 2003;290:1519-1520.
17. Silano M, De Vincenzi M, De Vincenzi A, Silano V. The new European legislation on traditional herbal medicines: main features and perspectives. Fitoterapia 2004;75:107-116.
18. Kernick D, White A. Applying economic evaluation to complementary and alternative medicine. In: Getting Health Economics into Practice, ed. Kernick DE. Oxford: Radcliffe Medical Press; 2002;173-180.
19. De Smet PAGM, Bonsel G, Van der Kuy A, et al. Introduction to the pharmacoeconomics of herbal medicines. Pharmacoeonomics 2000;18:1-7.
20. Rychlik R, Marshall M, Bachinger A, et al. Ökonomische Aspekte der Therapie der chronisch venösen Insuffizienz. Gesundh ökon Qual Manag 1997;2:86-91.
Do you know how many of your patients are taking herbal preparations? With the proliferation of herbal products, the number could be greater than you think. Between 1990 and 1997, the US population increased its use of herbal medicines by 380%.1 Total out-of-pocket expenditure for herbal medicines in 1997 was $5.1 billion.1Table 1 lists the 10 best-selling herbal medicines in the US.2
Safety issues related to herbal medicine are complex: possible toxicity of herbal constituents, presence of contaminants or adulterants, and potential interactions between herbs and prescription drugs. The quality of herbal medicines is often suboptimal. One reason for this is that they are not adequately regulated, and many experts are calling for a change in this situation. Cost-evaluations of herbal medicine are not available, so they cannot form the basis for clinical decisions.
This article provides guidelines for prescribing herbal medications appropriately.
TABLE 1
10 best-selling herbal medicines (United States, 2001)
| Rank | Herb | Retail sales |
|---|---|---|
| 1 | Ginkgo biloba | 46 |
| 2 | Echinacea | 40 |
| 3 | Garlic | 35 |
| 4 | Ginseng | 31 |
| 5 | Soy | 28 |
| 6 | Saw palmetto | 25 |
| 7 | St John’s wort | 24 |
| 8 | Valerian | 12 |
| 9 | Cranberry | 10 |
| 10 | Black cohosh | 10 |
| Retail sales are rounded figures in million US dollars. | ||
Efficacy
One of the first things to consider when a patient proposes trying an herbal medicine is efficacy. Data on efficacy of herbal medicines are incomplete, yet some treatments have shown promise. The critical question is, Does the remedy work for the patient’s condition? Clinicians should not prescribe or recommend herbal remedies if that question cannot be answered with a firm Yes.
Medical herbalism (ie, the medicinal use of preparations that contain exclusively plant material) once dominated our pharmacopeia but went into rapid decline when pharmacology established itself as a leading branch of therapeutics. During the last part of the 19th and the early 20th century, herbalism virtually vanished from the therapeutic map of the US and the UK. In contrast, many developing countries never abandoned medical herbalism (Ayurvedic medicine in India, Kampo medicine in Japan, and Chinese herbalism in China). In other countries (such as Germany and France), medical herbalism continued a “low-key” coexistence with modern pharmacology. More recently, herbal medicine has experienced a remarkable comeback.
Herbal medicines usually contain a range of pharmacologically active compounds. In some cases it is not known which of these constituents produces the therapeutic effect. Testing for efficacy in this situation is obviously more complex than with synthetic drugs. One approach is to view the entire herbal extract as the active component. To optimise the reproducibility of efficacy studies, extracts must be sufficiently characterised. This is often achieved by standardizing the amount of a single key constituent of the extract (eg, a pharmacologically active ingredient or, if such an ingredient is not known, a marker suitable substance).
Other than the dilemma of standardization, herbal medicines can be scrutinized in clinical trials in much the same way as are other drugs. Several randomized clinical trials of herbal medicines have been published, and systematic reviews/meta-analyses of these studies have become available (Table 2).3,4 The Cochrane database includes about 30 systematic reviews of herbal medicines, and several authoritative books have recently become available.3-6 The conclusions of systematic reviews are often limited by the paucity and varied methodological quality of the primary studies.3,7 Research funds in this area are generally scarce, not least because plants are not patentable.
Generalizations about efficacy of herbal medicines are not possible; each one must be judged on its own merits. Some herbal products have demonstrated efficacy for certain conditions, while others have not. Most products have not been submitted to extensive clinical testing.3 “Clinicians should not prescribe or recommend herbal remedies without well-established efficacy….”7
TABLE 2
Examples of systematic reviews and meta-analyses of herbal remedies
| Common (Latin) name | Active ingredients | Indications | No. of trials | Avg. methodological quality of primary studies | Efficacy | Main result |
|---|---|---|---|---|---|---|
| Feverfew (Tanacetum parthenium) | Parthenolide | Migraine prevention | 5 | Good | Likely | 3 trials were positive, 2 were negative |
| Garlic (Allium sativum) | Alliin | Hypercholesterolemia | 13 | Good (some excellent) | Certain but effect small | Overall effect is significant but of debateable clinical relevance |
| Ginkgo (Ginkgo biloba) | Ginkgolides, bilobalide | Intermittent claudication | 8 | Good to excellent | Certain | Overall positive result |
| Horse chestnut seed extract (Aesculus hippocastanum) | Triterpene saponins | Chronic venous insufficiency | 8/5* | Good | Likely | Active treatment more effective than placebo and equally effective as reference treatments |
| Peppermint oil (Menta x piperial)† | Menthol | Symptoms of irritable bowel syndrome | 8 | Good | Likely | Positive effect of peppermint oil compared with placebo |
| Sources: Ernst et al 20013; Fugh-Berman 2003.4 | ||||||
| *8 trials vs placebo; 5 trials vs reference treatments. † Am J Gastroenterol 1997; 93:1131–1135. | ||||||
Safety
Consumers are attracted to herbal medicines in part because they equate “natural” with “safe.” Yet some herbal medicines pose serious risks.7
First, the active ingredients in herbal preparations can, of course, cause desirable as well as undesirable effects. Table 3 lists examples of commonly used herbal medicines that have been associated with serious adverse effects.3 Traditional use is no guarantee of safety and no acceptable substitute for data.8
A poignant example is kava (Piper methysticum), an herbal remedy that has been used for centuries apparently without problems. Numerous rigorous clinical trials have shown it to be a powerful anxiolytic medicine.9 Recently it has been associated with several cases of serious liver damage.10 Hence it has been withdrawn from the markets of several European countries, and the FDA has issued warnings about its hepatotoxic potential.
Second, the active ingredients in herbal medicines might interact with prescription drugs. For instance, extracts of St. John’s wort (Hypericum perforatum) act as an enzyme inducer on the cytochrome P450 system and increase the activity of the P-glycoprotein transmembrane transporter mechanism. Both effects lead to a reduction of the plasma level of several conventional drugs.11 Perhaps the most serious consequence could be insufficiently low cyclosporine levels in patients after organ transplantation, which jeopardize the success of this procedure.12
Third, some herbal medicines (particularly Asian herbal mixtures) have repeatedly been shown to be contaminated with heavy metals,13 or to contain misidentified herbal ingredients that turned out to be toxic,14 or to be adulterated with prescription drugs.15
Before prescribing or recommending an herbal medication, clinicians must ensure that it cannot generate undue harm.
TABLE 3
Examples of herbal medicines associated with serious adverse effects
| Common (Latin) name | Indication | Adverse effects (examples) |
|---|---|---|
| Aloe vera (Aloe barbadensis) | Various | Juice may cause intestinal pain and electrolyte loss |
| Feverfew (Tanacetum parthenium) | Migraine prevention | “Post-fever syndrome” after discontinuation (migraine, anxiety, insomnia, muscle stiffness) |
| Hawthorn (Crataegus) | Congestive heart failure | Additive effects with other cardiac glycosides |
| Kava (Piper methysticum) | Anxiety | Toxic liver damage |
| St. John’s wort (Hypericum perforatum) | Depression | Increased clearance of a range of prescribeddrugs |
| Tea tree oil (Malaleuca alternifolia) | Skin problems (external) | Allergic reactions |
| Valerian (Valeriana officinalis) | Insomnia | Morning hangover |
| Without positive data demonstrating safety, herbal medications cannot automatically be considered safe for pregnant or nursing women. | ||
Quality
The quality of an herbal preparation partly determines its efficacy as well as its safety. Herbal dietary supplements are not usually regulated as drugs and have repeatedly been found to vary in quality, sometimes being suboptimal.7,16
In the US, such preparations have to meet the requirements set forth in the Dietary Supplement and Health Education Act (DSHEA) of 1994. Thus they are marketed without approval of their efficacy and safety by the FDA. The DSHEA does not allow medical claims to be made for such products. Structure or functional claims are, however, allowed. If safety concerns of a product arise, the burden of proof lies not with its manufacturer but with the FDA. Many experts find this regulation insufficient to guarantee consumer safety and argue for it to be changed.16 In Europe, new legislation will soon regulate herbal medicines. Essentially the legislation will provide that efficacy be demonstrated on the basis of bibliographic data; safety, too, will be governed as it is with conventional drugs.17
Cost
Clinicians should recommend treatments that save money for patients and the healthcare system. Many herbal medications are relatively inexpensive. However, very few proper economic analyses of herbal medicines exist.18,19 So far, only 1 cost evaluation of an herbal medicine has been published.20 This study of symptomatic treatment of chronic venous insufficiency compared the cost-effectiveness of compression stockings with that of an extract of horse chestnut seeds. Its results implied that the treatments were similarly effective and associated with similar costs.
For the prescribing physician, this means decisions cannot presently be based on conclusive cost-analyses. While waiting for such data to become available, decisions will have to be informed by our knowledge on the efficacy, safety, and quality of herbal medications.
Correspondence
Edzard Ernst, MD, PhD, Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, United Kingdom. E-mail: Edzard.Ernst@pms.ac.uk.
Do you know how many of your patients are taking herbal preparations? With the proliferation of herbal products, the number could be greater than you think. Between 1990 and 1997, the US population increased its use of herbal medicines by 380%.1 Total out-of-pocket expenditure for herbal medicines in 1997 was $5.1 billion.1Table 1 lists the 10 best-selling herbal medicines in the US.2
Safety issues related to herbal medicine are complex: possible toxicity of herbal constituents, presence of contaminants or adulterants, and potential interactions between herbs and prescription drugs. The quality of herbal medicines is often suboptimal. One reason for this is that they are not adequately regulated, and many experts are calling for a change in this situation. Cost-evaluations of herbal medicine are not available, so they cannot form the basis for clinical decisions.
This article provides guidelines for prescribing herbal medications appropriately.
TABLE 1
10 best-selling herbal medicines (United States, 2001)
| Rank | Herb | Retail sales |
|---|---|---|
| 1 | Ginkgo biloba | 46 |
| 2 | Echinacea | 40 |
| 3 | Garlic | 35 |
| 4 | Ginseng | 31 |
| 5 | Soy | 28 |
| 6 | Saw palmetto | 25 |
| 7 | St John’s wort | 24 |
| 8 | Valerian | 12 |
| 9 | Cranberry | 10 |
| 10 | Black cohosh | 10 |
| Retail sales are rounded figures in million US dollars. | ||
Efficacy
One of the first things to consider when a patient proposes trying an herbal medicine is efficacy. Data on efficacy of herbal medicines are incomplete, yet some treatments have shown promise. The critical question is, Does the remedy work for the patient’s condition? Clinicians should not prescribe or recommend herbal remedies if that question cannot be answered with a firm Yes.
Medical herbalism (ie, the medicinal use of preparations that contain exclusively plant material) once dominated our pharmacopeia but went into rapid decline when pharmacology established itself as a leading branch of therapeutics. During the last part of the 19th and the early 20th century, herbalism virtually vanished from the therapeutic map of the US and the UK. In contrast, many developing countries never abandoned medical herbalism (Ayurvedic medicine in India, Kampo medicine in Japan, and Chinese herbalism in China). In other countries (such as Germany and France), medical herbalism continued a “low-key” coexistence with modern pharmacology. More recently, herbal medicine has experienced a remarkable comeback.
Herbal medicines usually contain a range of pharmacologically active compounds. In some cases it is not known which of these constituents produces the therapeutic effect. Testing for efficacy in this situation is obviously more complex than with synthetic drugs. One approach is to view the entire herbal extract as the active component. To optimise the reproducibility of efficacy studies, extracts must be sufficiently characterised. This is often achieved by standardizing the amount of a single key constituent of the extract (eg, a pharmacologically active ingredient or, if such an ingredient is not known, a marker suitable substance).
Other than the dilemma of standardization, herbal medicines can be scrutinized in clinical trials in much the same way as are other drugs. Several randomized clinical trials of herbal medicines have been published, and systematic reviews/meta-analyses of these studies have become available (Table 2).3,4 The Cochrane database includes about 30 systematic reviews of herbal medicines, and several authoritative books have recently become available.3-6 The conclusions of systematic reviews are often limited by the paucity and varied methodological quality of the primary studies.3,7 Research funds in this area are generally scarce, not least because plants are not patentable.
Generalizations about efficacy of herbal medicines are not possible; each one must be judged on its own merits. Some herbal products have demonstrated efficacy for certain conditions, while others have not. Most products have not been submitted to extensive clinical testing.3 “Clinicians should not prescribe or recommend herbal remedies without well-established efficacy….”7
TABLE 2
Examples of systematic reviews and meta-analyses of herbal remedies
| Common (Latin) name | Active ingredients | Indications | No. of trials | Avg. methodological quality of primary studies | Efficacy | Main result |
|---|---|---|---|---|---|---|
| Feverfew (Tanacetum parthenium) | Parthenolide | Migraine prevention | 5 | Good | Likely | 3 trials were positive, 2 were negative |
| Garlic (Allium sativum) | Alliin | Hypercholesterolemia | 13 | Good (some excellent) | Certain but effect small | Overall effect is significant but of debateable clinical relevance |
| Ginkgo (Ginkgo biloba) | Ginkgolides, bilobalide | Intermittent claudication | 8 | Good to excellent | Certain | Overall positive result |
| Horse chestnut seed extract (Aesculus hippocastanum) | Triterpene saponins | Chronic venous insufficiency | 8/5* | Good | Likely | Active treatment more effective than placebo and equally effective as reference treatments |
| Peppermint oil (Menta x piperial)† | Menthol | Symptoms of irritable bowel syndrome | 8 | Good | Likely | Positive effect of peppermint oil compared with placebo |
| Sources: Ernst et al 20013; Fugh-Berman 2003.4 | ||||||
| *8 trials vs placebo; 5 trials vs reference treatments. † Am J Gastroenterol 1997; 93:1131–1135. | ||||||
Safety
Consumers are attracted to herbal medicines in part because they equate “natural” with “safe.” Yet some herbal medicines pose serious risks.7
First, the active ingredients in herbal preparations can, of course, cause desirable as well as undesirable effects. Table 3 lists examples of commonly used herbal medicines that have been associated with serious adverse effects.3 Traditional use is no guarantee of safety and no acceptable substitute for data.8
A poignant example is kava (Piper methysticum), an herbal remedy that has been used for centuries apparently without problems. Numerous rigorous clinical trials have shown it to be a powerful anxiolytic medicine.9 Recently it has been associated with several cases of serious liver damage.10 Hence it has been withdrawn from the markets of several European countries, and the FDA has issued warnings about its hepatotoxic potential.
Second, the active ingredients in herbal medicines might interact with prescription drugs. For instance, extracts of St. John’s wort (Hypericum perforatum) act as an enzyme inducer on the cytochrome P450 system and increase the activity of the P-glycoprotein transmembrane transporter mechanism. Both effects lead to a reduction of the plasma level of several conventional drugs.11 Perhaps the most serious consequence could be insufficiently low cyclosporine levels in patients after organ transplantation, which jeopardize the success of this procedure.12
Third, some herbal medicines (particularly Asian herbal mixtures) have repeatedly been shown to be contaminated with heavy metals,13 or to contain misidentified herbal ingredients that turned out to be toxic,14 or to be adulterated with prescription drugs.15
Before prescribing or recommending an herbal medication, clinicians must ensure that it cannot generate undue harm.
TABLE 3
Examples of herbal medicines associated with serious adverse effects
| Common (Latin) name | Indication | Adverse effects (examples) |
|---|---|---|
| Aloe vera (Aloe barbadensis) | Various | Juice may cause intestinal pain and electrolyte loss |
| Feverfew (Tanacetum parthenium) | Migraine prevention | “Post-fever syndrome” after discontinuation (migraine, anxiety, insomnia, muscle stiffness) |
| Hawthorn (Crataegus) | Congestive heart failure | Additive effects with other cardiac glycosides |
| Kava (Piper methysticum) | Anxiety | Toxic liver damage |
| St. John’s wort (Hypericum perforatum) | Depression | Increased clearance of a range of prescribeddrugs |
| Tea tree oil (Malaleuca alternifolia) | Skin problems (external) | Allergic reactions |
| Valerian (Valeriana officinalis) | Insomnia | Morning hangover |
| Without positive data demonstrating safety, herbal medications cannot automatically be considered safe for pregnant or nursing women. | ||
Quality
The quality of an herbal preparation partly determines its efficacy as well as its safety. Herbal dietary supplements are not usually regulated as drugs and have repeatedly been found to vary in quality, sometimes being suboptimal.7,16
In the US, such preparations have to meet the requirements set forth in the Dietary Supplement and Health Education Act (DSHEA) of 1994. Thus they are marketed without approval of their efficacy and safety by the FDA. The DSHEA does not allow medical claims to be made for such products. Structure or functional claims are, however, allowed. If safety concerns of a product arise, the burden of proof lies not with its manufacturer but with the FDA. Many experts find this regulation insufficient to guarantee consumer safety and argue for it to be changed.16 In Europe, new legislation will soon regulate herbal medicines. Essentially the legislation will provide that efficacy be demonstrated on the basis of bibliographic data; safety, too, will be governed as it is with conventional drugs.17
Cost
Clinicians should recommend treatments that save money for patients and the healthcare system. Many herbal medications are relatively inexpensive. However, very few proper economic analyses of herbal medicines exist.18,19 So far, only 1 cost evaluation of an herbal medicine has been published.20 This study of symptomatic treatment of chronic venous insufficiency compared the cost-effectiveness of compression stockings with that of an extract of horse chestnut seeds. Its results implied that the treatments were similarly effective and associated with similar costs.
For the prescribing physician, this means decisions cannot presently be based on conclusive cost-analyses. While waiting for such data to become available, decisions will have to be informed by our knowledge on the efficacy, safety, and quality of herbal medications.
Correspondence
Edzard Ernst, MD, PhD, Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, United Kingdom. E-mail: Edzard.Ernst@pms.ac.uk.
1. Eisenberg DM, David RB, Ettner SL, et al. Trends in alternative medicine use in the United States. JAMA 1998;280:1569-1575.
2. Blumenthal M. Herb sales down in mainstream market, up in natural food stores. Herbal Gram 2002;55:60.-
3. Ernst E, Pittler MH, Stevinson C, White AR. The Desktop Guide to Complementary and Alternative Medicine. Edinburgh: Mosby; 2001.
4. Fugh-Berman A. The 5-minute herb & dietary supplement consult. Philadelphia: Lippincott Williams & Wilkins; 2003.
5. Capasso F, Gaginella TS, Grandolini G, Izzo AA. Phytotherapy: A Quick Reference to Herbal Medicine. Berlin: Springer-Verlag; 2003.
6. Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy. Berlin: Springer-Verlag; 2001.
7. De Smet PAGM. Herbal remedies. N Engl J Med 2002;347:2046-2056.
8. Ernst E, De Smet PAGM, Shaw D, Murray V. Traditional remedies and the “test of time.” Eur J Clin Pharmacol 1998;54:99-100.
9. Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Library 2002.
10. Teschke R, Gaus W, Loew D. Kava extracts: safety and risks including rare hepatotoxicity. Phytomed 2003;10:440-446.
11. Carlo GD, Borrelli F, Ernst E, Izzo AA. St. John’s wort: Prozac from the plant kingdom. TRENDS in Pharmacol Sci 2001;22:292-297.
12. Ernst E. St John’s wort supplements endanger the success of organ transplantation. Arch Surg 2002;137:316-319.
13. Ernst E, Thompson Coon J. Heavy metals in traditional Chinese medicines: a systematic review. Clin Pharmacol Ther 2001;70:497-504.
14. Nortier JL, Muniz Martinez. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 2000;342:1686-1692.
15. Ernst E. Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review. J Int Med 2002;251:107-113.
16. De Angelis CD, Fontanarosa PB. Drugs alias dietary supplements. JAMA 2003;290:1519-1520.
17. Silano M, De Vincenzi M, De Vincenzi A, Silano V. The new European legislation on traditional herbal medicines: main features and perspectives. Fitoterapia 2004;75:107-116.
18. Kernick D, White A. Applying economic evaluation to complementary and alternative medicine. In: Getting Health Economics into Practice, ed. Kernick DE. Oxford: Radcliffe Medical Press; 2002;173-180.
19. De Smet PAGM, Bonsel G, Van der Kuy A, et al. Introduction to the pharmacoeconomics of herbal medicines. Pharmacoeonomics 2000;18:1-7.
20. Rychlik R, Marshall M, Bachinger A, et al. Ökonomische Aspekte der Therapie der chronisch venösen Insuffizienz. Gesundh ökon Qual Manag 1997;2:86-91.
1. Eisenberg DM, David RB, Ettner SL, et al. Trends in alternative medicine use in the United States. JAMA 1998;280:1569-1575.
2. Blumenthal M. Herb sales down in mainstream market, up in natural food stores. Herbal Gram 2002;55:60.-
3. Ernst E, Pittler MH, Stevinson C, White AR. The Desktop Guide to Complementary and Alternative Medicine. Edinburgh: Mosby; 2001.
4. Fugh-Berman A. The 5-minute herb & dietary supplement consult. Philadelphia: Lippincott Williams & Wilkins; 2003.
5. Capasso F, Gaginella TS, Grandolini G, Izzo AA. Phytotherapy: A Quick Reference to Herbal Medicine. Berlin: Springer-Verlag; 2003.
6. Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy. Berlin: Springer-Verlag; 2001.
7. De Smet PAGM. Herbal remedies. N Engl J Med 2002;347:2046-2056.
8. Ernst E, De Smet PAGM, Shaw D, Murray V. Traditional remedies and the “test of time.” Eur J Clin Pharmacol 1998;54:99-100.
9. Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Library 2002.
10. Teschke R, Gaus W, Loew D. Kava extracts: safety and risks including rare hepatotoxicity. Phytomed 2003;10:440-446.
11. Carlo GD, Borrelli F, Ernst E, Izzo AA. St. John’s wort: Prozac from the plant kingdom. TRENDS in Pharmacol Sci 2001;22:292-297.
12. Ernst E. St John’s wort supplements endanger the success of organ transplantation. Arch Surg 2002;137:316-319.
13. Ernst E, Thompson Coon J. Heavy metals in traditional Chinese medicines: a systematic review. Clin Pharmacol Ther 2001;70:497-504.
14. Nortier JL, Muniz Martinez. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 2000;342:1686-1692.
15. Ernst E. Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review. J Int Med 2002;251:107-113.
16. De Angelis CD, Fontanarosa PB. Drugs alias dietary supplements. JAMA 2003;290:1519-1520.
17. Silano M, De Vincenzi M, De Vincenzi A, Silano V. The new European legislation on traditional herbal medicines: main features and perspectives. Fitoterapia 2004;75:107-116.
18. Kernick D, White A. Applying economic evaluation to complementary and alternative medicine. In: Getting Health Economics into Practice, ed. Kernick DE. Oxford: Radcliffe Medical Press; 2002;173-180.
19. De Smet PAGM, Bonsel G, Van der Kuy A, et al. Introduction to the pharmacoeconomics of herbal medicines. Pharmacoeonomics 2000;18:1-7.
20. Rychlik R, Marshall M, Bachinger A, et al. Ökonomische Aspekte der Therapie der chronisch venösen Insuffizienz. Gesundh ökon Qual Manag 1997;2:86-91.