Echinacea: Remedy or Ruse?
abstract & commentarySource: Grimm W, Muller HH. A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infection. Am J Med 1999;106:138-143.
Echinacea purpurea, derived from those beautiful purple cone flowers in your garden, has been widely used for the prevention and treatment of colds and respiratory infection. Despite its popularity (Grimm and Muller point out that Germans alone spent 45 million marks on echinacea-based products in 1993), controversy exists regarding the value of this product. Grimm and Muller randomly assigned 108 patients with a history of three or more respiratory infections during the past year to receive either daily echinacea extract or a matching placebo for eight weeks, during which time the frequency and severity of respiratory illness was assessed. The extracts were prepared from the freshly expressed juices of the whole flowering plant without its roots, and contained 22% alcohol. Patients were instructed to note any symptoms suggestive of upper respiratory illness, including burning eyes, headache, joint pain, myalgia, as well as generalized weakness and fatigue. The presence and severity of illness was clinically assessed by one of two practitioners blinded to the study medication.
Unfortunately, no significant difference in the incidence, duration, or severity of colds and respiratory infections between the two groups was found. During the eight weeks of follow-up, 65% of patients receiving echinacea and 74% of the control group had at least one cold or upper respiratory illness (RR = 0.88; P = 0.33). Nevertheless, nearly half of the participants wished to continue their study medication after completion of the study, including 43% of the placebo group.
Comment by Carol A. Kemper, MD
Various plant parts of several different Echinacae species have been the basis of investigation in recent years, with lots of tantalizing in vitro and in vivo data in mice and humans demonstrating potentially beneficial immunomodulatory properties. Polysaccharide extracts of E. purpurea activate murine and human monocytes and macrophages in vitro, resulting in increased IL-1, IL-6, IL-10, and TNF-a production.1-3 Peritoneal macrophages from immunodeficient mice treated with polysaccharide extract of echinacea exhibit increased production of TNF, as well as enhanced cytotoxicity against Leishmania enrietti and tumor cells.4 Most compelling was data suggesting a protective effect of echinacea extracts administered for three days to mice subsequently challenged with lethal doses of Listeria monocytogenes and Candida albicans.5
In addition to its potential immunomodulatory effects, echinacea may have direct antiviral properties, although the data are limited. Thompson demonstrated that a topical blend of phytochemicals of echinacea had reasonable activity in vitro against both acyclovir-susceptible and acyclovir-resistant strains of HSV-1 and HSV-2.8
On the other hand, a number of studies demonstrate negative results.6,7 For example, following the administration of echinacea for four weeks to 23 patients with malignancy undergoing chemotherapy, cultured supernatants of peripheral blood cells produced levels of cytokines similar to that of cells obtained from untreated control subjects.7
Clinical trials in humans have also yielded conflicting results. Two earlier clinical studies reportedly found that treatment with echinacea products decreased the duration and severity of symptoms associated with upper respiratory tract infection (URTI).9,10 However, these papers, written in German, are not included in Medline and have not been accessible. Unfortunately, Grimm and Muller found no such benefit in their study. Daily echinacea did not appear to prevent URTI in highly susceptible patients, nor did it appear to have an effect on the signs and symptoms of illness once it occurred. Additional work performed at the Center for Complementary Medicine Research in Munich involving 302 military personnel and employees of a large industrial plant also failed to demonstrate that ethanolic extracts from either of two different species of echinacea were more effective than placebo in the prevention of URTI.11 While 37% of patients in the placebo group developed a cold or upper respiratory illness, 32% of those receiving extracts of E. angustifolia and 29% receiving E. purpurea developed a URTI (RR = 0.8; 95% CI, 0.53-1.31). The median time to upper respiratory infection was slightly more than two months, irrespective of the group assignment.
It is not surprising that variable results may have been reported. Different echinacea species and plant parts, which may have varying levels of activity, have been variously used for study. In addition, Grimm and Muller note that the study medication in one of the earlier reports contained at least 50% alcohol, which could theoretically counteract any beneficial cellular effects (it’s no wonder that half the participants wished to continue their study medication!). The unusually high frequency of apparent upper respiratory illness seen in the group of patients studied by Grimm and Muller suggests that perhaps some suffered from recurrent allergic symptoms and not viral respiratory infection, in which case, echinacea would not be expected to have an effect. Furthermore, none of these earlier studies was sufficiently powered to detect smaller differences in therapeutic outcome (e.g., 10-20%).
Nevertheless, data providing support for its immunomodulatory properties and effectiveness in humans, as well as the widespread popularity of this product, appear sufficiently compelling to warrant its further study. Participants in future studies should be aware, however, that little-known side effects, such as the possible inhibition of sperm enzymes and motility, may occur.12 In vitro work by Ondrizek and colleagues on washed sperm showed that sperm motility and velocity were significantly inhibited at 24 and 48 hours by high concentrations of saw palmetto, St. John’s wort, ginkgo, and echinacea.
Based on a lack of conclusive data demonstrating its clinical effectiveness, the German health board recently elected to exclude echinacea from its formulary. Although working with natural products, for which standardization is an issue, provides a challenge to investigators, clinical trials could be better designed to examine the effectiveness of these products. For example, basing the assessment on the results of nasopharyngeal swabs for culture, DFA for respiratory viruses, and swab cultures for Streptococcus pyogenes would provide firmer endpoints for study. In addition, studies could be designed using intranasal preparations of Corona virus as a therapeutic challenge.
With billions of dollars at stake in the health food industry, the results of these kinds of studies are going to become increasingly important. Large pharmaceutical companies are attempting to obtain marketing rights to many natural products and dietary supplements, and some believe they are laying the groundwork for control of the health food industry. Despite the fact that two large European pharmaceutical companies made headline news and were fined $500 million for price fixing the vitamin market, the pharmaceutical industry is pushing the ECC to adopt international standards for regulating natural foods and dietary supplements. Under GATT, the United States may be obligated to follow suit.
For example, a recent proposal set forth by the German delegation to the United Nations/World Health Organization commission to establish worldwide standards for food and drugs states that no minerals, herbs, or vitamins can be sold for prophylactic or therapeutic use without authorization, and none can be sold in excess of established dose limits. Canada’s new Food and Drug Policy restricts the sale of any substance with therapeutic effect or medical claims (e.g., St. John’s wort). It is anticipated that the attendant regulation required for registration and approval of any new product will cause Canadian prices of herbal/nutritional products to double.
To be sure, consumer protection and product safety is an important government function, but do we really want only patented, pharmaceutical versions of common herbs and dietary supplements, such as ginger and St. John’s wort? We should decide whether such substances should be required to meet the same safety and efficacy standards as other drugs, and how accessible they will remain without prescription in the future. v
References
1. Roesler J, et al. Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system. Int J Immunopharmacol 1991;13:931-941.
2. Burger R, et al. Echinacea-induced cytokine production by human macrophages. Int J Immunopharmacol 1997;19:371-379.
3. Stimpel M, et al. Macrophage activation and induction of macrophage cytotoxicity by purifed polysaccharide fractions from the plant Echinacea purpurea. Infect Immun 1984;46:845-849.
4. Steinmuller C, et al. Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenes. Int J Immunopharmacol 1993;15: 605-614.
5. Roesler J, et al. Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to mice mediates protection against systemic infections with Listeria monocytogenes and Candida albicans. Int J Immunopharmacol 1991;13:27-37.
6. Melchart D, et al. Results of five randomized studies on the immunomodulatory activitity of preparations of Echinacea. J Altern Complement Med 1995;1:145-160.
7. Elsasser-Beile U, et al. Cytokine production in leukocyte cultures during therapy with Echinacea extract. J Clin Lab Anal 1996;10:441-445.
8. Thompson KD. Antiviral activity of Viracea against acyclovir susceptible and acyclovir resistant strains of herpes simplex virus. Antiviral Res 1998;39:55-61.
9. Brauning B, et al. Echinacea purpurea radix. Z Phytother 1992;13:7-13.
10. Brauning B, Knick E. Therapeutische erfahrungen mit Echnicaea pallidae bei grippalen infekten. Naturheilpraxis 1993;1:72-75.
11. Echinacea root extracts for the prevention of upper respiratory tract infections: A double-blind, placebo-controlled randomized trial. Arch Fam Med 1998;7: 541-545.
12. Ondrizek RR, et al. Inhibition of human sperm motility by specific herbs used in alternative medicine. J Assist Reprod Genet 1999;16:87-91.
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