By David Kiefer, MD
Echinacea products continue to represent both the popular use of herbal remedies by the general public and the uncertainty and even controversy in the scientific and medical communities about proper and proven indications. Recent clinical trials and review articles have shed some light on these issues, expanding on the information provided in past reviews published in this newsletter by Udani and Ofman,1 and Kattapong.2 It is important for physicians to know what to tell patients taking echinacea as a "cure" for the common cold or for its other popular uses.
Traditional Uses
The name echinacea comes from a genus (Echinacea) of plants in the daisy family (Asteraceae, also includes chamomile and milk thistle); these plants are native to North America and commonly are referred to as purple coneflower, a name immediately obvious given the shape and color of the flowering parts. There are many species and varieties of echinacea, though three of them are the ones primarily used medicinally. Until recently, the medicinally used species were called Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea; these are also the names that show up in the medical literature as detailed below.
Recent taxonomic work has clarified the correct naming of these species. According to this analysis, E. purpurea remains its own species, as does E. pallida.3 However, E. pallida includes many different varieties, including Echinacea pallida var. angustifolia, the new name for Echinacea angustifolia. Of these, E. purpurea is the most widely cultivated and used species.4
Native Americans were the first to use echinacea for medicinal purposes, the specifics of which were continued and expanded upon by a variety of practitioners who prescribed herbal medicines (including the Eclectic physicians, homeopaths, and naturopaths) in the late 1800s and early 1900s in the United States.4,5 At that time, echinacea was recommended for a variety of ailments, including snakebite, syphilis, cancer, dysentery, scarlet fever, and other infectious diseases.4,5
Contemporary Uses
Modern times have seen a resurgence in interest and use of echinacea. In Germany, the largest market for echinacea in Europe, general acceptance of herbal medicines and popularity of echinacea follow a long tradition of research in botanical medicine. However, the United States has begun to catch up in research and market sales.5
Mechanism of Action
There are numerous in vitro and animal studies showing the effect of echinacea on various immune system parameters.5 Most of these studies demonstrate that echinacea increases macrophage phagocytosis, and stimulates other monocytes, natural killer cells, and polymorphonuclear cells. In addition, echinacea may enhance antibody responses and increase levels of certain interleukins, tumor necrosis factor, and interferon.
The specific effects on the immune system have been found to be variable, a function of the plant part, extraction process, and species used.5 Of the many phytochemicals present in echinacea, most of the immune system effects derive from the polysaccharides, glycoproteins, and alkylamides.4,5 Of note, it is the alkylamides that account for the tingling sensation in the mouth caused by some echinacea tinctures, though these compounds are absent in E. pallida.
In vitro and animal studies have also demonstrated anti-inflammatory effects; echinacea inhibits hyaluronidase, cyclooxygenase, and 5-lipoxygenase via its cichoric acid, and alkylamide compounds.4,5 E. purpurea may act as an inhibitor of COX-I and COX-II enzymes, or the nitric oxide synthase system.6
Other studies have demonstrated antifungal effects (such as against Candida albicans); there is disagreement about the quality of evidence for direct anti-viral effects.4,5
Clinical Trials
The latest review on echinacea in this newsletter2 described some of the clinical trials investigating the use of echinacea for colds, citing overall a lack of evidence, some possible benefit in treating colds, and no demonstrated efficacy in preventing colds.2 Since then, there has been further research defining the role of echinacea in the common cold.
A recent trial investigated the safety and efficacy of echinacea in treating upper respiratory infections (URI) in children.7 Healthy children ages 2-11 were randomized to receive echinacea or placebo for up to three URIs over a four-month period. The treatment product was dried pressed E. purpurea juice of the above-ground plant parts combined with syrup dosed at 50-67% of the adult dose twice a day; the placebo was only syrup. The researchers analyzed 707 URIs in 407 children focusing on duration and severity of URIs and adverse events.
There was no significant difference between the two groups with respect to duration of symptoms, severity of symptoms, days of fever, peak severity of symptoms, and number of days of peak severity. There also was no significant difference in rates of adverse events between the two groups, except for a slightly higher rate of rash in the echinacea group (7.1%) as compared to the placebo group (2.7%, P = 0.008). The results of this study do not support the use of this product and this dosing regimen in children as an URI treatment.
Another study examined the use of echinacea in treating the common cold in a college student population.8 One hundred forty-eight students were randomized to receive either a dried, whole-plant, unrefined echinacea capsule (50% E. purpurea, 50% E. angustifolia) or placebo (a capsule containing alfalfa) on the first day of a URI. No statistically significant differences were noted in any of the parameters measured, including self-reported severity and duration of symptoms. Also, there were no statistical differences between the two groups in reports of adverse effects. Although clearly a negative trial, the authors mention that it may be a result of an ineffective or bio-unavailable formulation, the use of self-reported symptoms, or the healthy college population studied.
In one study, 80 adult employees of a German company were randomly allocated at the first signs of a common cold to receive either a placebo or a specific echinacea extract (EC31J0, the juice expressed from the fresh, above-ground parts of E. purpurea) for 10 days.9 This double-blind trial then used the number of days of illness as the primary endpoint. The echinacea-treated group had a mean number of illness days of six, as compared to nine in the placebo group, a statistically significant finding. There were no relevant differences between the two groups with respect to adverse events, and there were no serious reactions. One researcher pointed out some of the weaknesses of this trial, including a lack of evidence of blinding, unclear data analysis, and the use of unvalidated measures.5
Another study looked at the use of an echinacea tea product.10 The researchers in this double-blind, placebo-controlled study randomized 95 people (81 women, 14 men) with early symptoms of a cold to drink 5-6 cups of a proprietary echinacea tea (made out of leaves, flowers, and stems of E. angustifolia and E. purpurea, as well as a small amount of lemongrass and spearmint) daily for five days or a placebo drink (made out of ginger, peppermint, and cinnamon). A self-scoring, three-part questionnaire revealed that the group assigned to echinacea tea had significantly fewer days of cold symptoms, more effective symptom relief, and more days of noticeable symptom change. Some problems with this study include no evidence of blinding and a poor outcome measure (a retrospective assessment).5
Other Literature
In addition to the individual clinical trials mentioned above, readers should be aware of literature reviews examining the topic of echinacea in the treatment or prevention of the common cold.11,12 In general, these authors underscore the inability to make specific recommendations regarding the use of echinacea given the significant heterogeneity in research trials, including the form and species of plant used, as well as the large variation in the methodological quality of the research conducted. However, the authors note that most of the studies report positive results in the treatment of the common cold early in its course.
Furthermore, in an effort to translate some of the in vitro and animal research results of echinacea’s effect on the immune system to humans, researchers examined the effect of orally administered juice from fresh E. purpurea on various immune system parameters of 40 healthy men in a double-blind, placebo-controlled crossover trial.13 Two treatment periods of 14 days separated by a washout period of one month failed to show any differences between the echinacea group and placebo group on phagocytic activity of polymorphonuclear leukocytes or monocytes, or on the production of TNF-alpha or IL-1beta. This study conflicts with past research showing that echinacea does modulate several different immunological parameters;5 there is still debate about the exact mechanism of action as well as which forms of the herb might be most active and for which people.
As mentioned above, there are methodological flaws in some of the research evaluating the therapeutic actions of echinacea that make practical application of the data problematic. For example, studies may not mention the species of echinacea used,14 or use a variety of forms and preparations that complicate the final assessment.
Adverse Effects and Contraindications
Adverse reactions to echinacea are rare and mild, most often involving gastrointestinal distress or dizziness.15,16 Allergic reactions, including anaphylaxis, angioedema, and exacerbation of asthma, have been documented especially in people with atopic conditions or a history of allergies to plants in the daisy family (which includes ragweed, sagebrush, marigolds, and sunflowers).16,17
Some authors advise against the long-term use of echinacea due to the possibility for immunosuppression18,19 and because of the lack of evidence for efficacy in prevention of URIs. Others note that due to this possibility for immunosuppression, as well as the above-mentioned immune system stimulation, echinacea is contraindicated for long-term use in patients for whom immune system depression (i.e., AIDS) or enhancement (i.e., autoimmune disorders, tuberculosis, multiple sclerosis, during immunosuppressive therapy, etc.) would have serious consequences.18-20 These are, however, theoretical possibilities that have yet to be documented in humans.16
Recommendations for the oral use of echinacea in pregnant or lactating women vary, from avoidance due to a lack of information21 to no effects or warnings listed.19 One recent cohort study compared 206 women who had used echinacea during pregnancy to 206 women in a control group; there were no significant differences in the rates of major malformations, minor malformations, miscarriages, or neonatal complications between the two groups.22
Echinacea Preparations
There are a wide variety of echinacea formulations available in the current dietary supplement market, including variable combinations of the three medicinally active species, the plant parts used, the extraction process, and the final form of the plant. Another compounding factor is the frequent lack of correlation between listed label contents and the actual amount of echinacea in a given product;22 there is, however, difficulty in arriving at consensus about correct assay protocols for the phytochemicals listed in a standardized product.
Dosage
Recommended dosage of echinacea depends on the form, the product, and the source consulted. The usual range is 900-1,000 mg three times a day, 6-9 mL of pressed juice daily, or 0.75-1.5 mL of tincture daily;15 some authors recommend higher doses in the early stages of a cold, tapering off over the course of 7-10 days.16 Echinacea tea is ingested 6-8 oz four times daily for days 1-2 of a cold, down to once or twice daily for the remainder of a week.16
Conclusion
Evidence continues to accumulate about the use of echinacea in treating and preventing the common cold. As noted, there is still a problem in arriving at specific recommendations on the use of echinacea given the heterogeneity in form and species of plant used, as well as the large variation in methodological quality of the research conducted.
A review of some recent trials, however, suggests that echinacea is not useful in treating URIs in healthy children or college students. Two other trials did, however, show some benefit in treating the common cold in adults. Any conclusions that are drawn from these results, or attempts to extrapolate the data, must take into consideration the different types of extracts used, the plant species involved, and the populations being studied.
There are some groups of people for whom echinacea is not appropriate, including atopic individuals who might be at a greater risk for an allergic reaction to these plants.
Recommendation
Uncertainties remain about which form of echinacea to recommend and for which populations. However, with a paucity of effective cold treatments in the conventional medical armamentarium, for most people echinacea is safe, well-tolerated, and potentially effective. Echinacea may be a reasonable treatment choice for adults if used early in the course of an upper respiratory infection. The most favorable studies used an extract of the juice of fresh E. purpurea; dried forms of the herb in the few studies available seem to be less effective. Caution is advised in atopic individuals and in people for whom any immunomodulatory effects might be detrimental.
Dr. Kiefer recently completed a fellowship at the Program in Integrative Medicine, College of Medicine, University of Arizona, Tucson.
References
1. Udani JK, Ofman JJ. Echinacea for the common cold. Altern Med Alert 1998;1:16-18.
2. Kattapong VJ. Echinacea for colds. Altern Med Alert 2000;3:128-130.
3. Binns SE, et al. A taxonomic revision of echinacea (Asteraceae: Heliantheae). Systematic Botany 2002;27:610-632.
4. Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh, England: Churchill Livingstone; 2000.
5. Barrett B. Medicinal properties of echinacea: A critical review. Phytomedicine 2003;10:66-86.
6. Clifford LJ, et al. Bioactivity of alkamides isolated from Echinacea purpurea (L.) Moench. Phytomedicine 2002;9:249-253.
7. Taylor JA, et al. Efficacy and safety of echinacea in treating upper respiratory tract infections in children: A randomized controlled trial. JAMA 2003;290: 2824-2830.
8. Barrett BP, et al. Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2002;137: 939-946.
9. Schulten B, et al. Efficacy of Echinacea purpurea in patients with a common cold: A placebo-controlled, randomised, double-blind clinical trial. Arzneimittelforschung 2001;51:563-568.
10. Lindenmuth GF, Lindenmuth EB. The efficacy of echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: A randomized, double-blind placebo-controlled study. J Altern Complement Med 2000;6:327-334.
11. Barrett B, et al. Echinacea for upper respiratory infection. J Fam Pract 1999;48:628-635.
12. Melchart D, et al. Echinacea for preventing and treating the common cold (Cochrane Review). In: The Cochrane Library. Issue 1. Chichester, UK: John Wiley & Sons, Ltd.; 2004.
13. Schwarz E, et al. Oral administration of freshly expressed juice of Echinacea purpurea herbs fail to stimulate the nonspecific immune response in healthy young men: Results of a double-blind, placebo-controlled crossover study. J Immunother 2002;25: 413-420.
14. Turner RB, et al. Ineffectiveness of echinacea for prevention of experimental rhinovirus colds. Antimicrob Agents Chemother 2000;44:1708-1709.
15. Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John’s wort, ginseng, echinacea, saw palmetto, and kava. Ann Intern Med 2002;136:42-53.
16. Kligler B. Echinacea. Am Fam Phys 2003;67:77-80.
17. Mullins RJ, Heddle R. Adverse reactions associated with echinacea: The Australian experience. Ann Allergy Asthma Immunol 2002;88:42-51.
18. Kemp DE, Franco KN. Possible leukopenia associated with long-term use of echinacea. J Am Board Fam Pract 2002;15:417-419.
19. Blumenthal M, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; 1998.
20. Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy, OR: Eclectic Medical Publications; 2001.
21. Gallo M, et al. Pregnancy outcome following gestational exposure to echinacea: A prospective controlled study. Arch Intern Med 2000;160:3141-3143.
22. Gilroy CM, et al. Echinacea and truth in labeling. Arch Intern Med 2003;163:699-704.
Kiefer D. Echinacea: An update on the popular cold cure. Altern Med Alert 2004;7(4):41-44.
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