Echinacea

Common Names: Purple coneflower, Coneflower, Combflower, Black Sampson, Missouri Snake Root, Kansas Snake Root

Clinical Names: Echinacea angustifolia, E. purpurea, E. pallida

Summary

botanical names: Echinacea purpurea, Echinacea angustifolia, Echinacea pallida.

common names: Purple coneflower, Coneflower, Missouri Snake Root (E. purpurea), Kansas Snake Root (E. angustifolia).

overview of interactions:
• herb affecting drug performance: immuno-suppressive therapy (theoretical): Cyclosporine

• herb affecting drug performance: Chemotherapy

• herb affecting drug performance: Econazole

• general herbal concern: Autoimmune conditions (controversial).

AHPA Botanical Safety Rating: 1




Clinical

botanical names: Echinacea purpurea, Echinacea angustifolia, Echinacea pallida.

common names: Purple coneflower, Coneflower, Combflower, Black Sampson, Missouri Snake Root (E. purpurea) Kansas Snake Root (E. angustifolia).

parts used: Roots, leaves, flowers and seeds.

actions: Alterative, immune stimulant, anti-inflammatory, antimicrobial, antiseptic, vulnerary.

dosage:
• dried root (decoction) : 1 oz. root to 1 pint water; drink one half to one full cup, up to four times a day.
• tincture (1:5) : 2 - 8 ml., three times a day.
• dried root powder : 1000 mg., three times a day.
• fresh juice (aerial parts) : 5 ml., three times a day.

therapy:
• internal: Viral and bacterial infections, especially chronic infections of the respiratory tract, prophylaxis of colds and influenza, immunodepression, mild septicemia, furunculosis.
• external: chronic ulcerations, bites and stings, (especially snake bites) skin complaints, urticaria, abcesses, gum disease (as mouthwash).

AHPA Botanical Safety Rating: 1

toxicity:
• Contact dermatitis is rare but has been reported in patients with known sensitivity to Asteraceae species . A single report of anaphylaxis has been published. (Mullins RJ.1998.)
• Caution during pregnancy.
(Mengs U, et al.Arzneimittelforschung 1991 Oct;41(10):1076-1081; Mullins RJ. Med J Aust 1998 Feb 16;168 (4):170-171.)

contraindications:
• For full discussion of limitations of Echinacea use controversy, see commentary below.
• According to Commission E and related German sources, Echinacea spp. are contraindicated in "progressive systemic disease conditions" such as multiple sclerosis, collagenosis, leukosis and auto-immune disorders ; probably due to non-specific stimulation of the immune response.
(Blumenthal M, et al. 1998, De Smet PGAM, et al. 1993.)
• The same sources state Echinacea spp. contraindicated in AIDS or HIV infection possibly due arabinogalactans (not present in filtered hydroethanolic extracts) inducing secretion by macrophages of tumor necrosis factor alpha which is elevated in the serum of patients with AIDS cachexia.
(Bodinet C, et al. Planta Med 1993;59 (Suppl.):A672.)
• The same sources state Echinacea spp. contraindicated in tuberculosis probably since arabinogalactan constituents are similar to those in Mycobacteria cell walls associated with cell-mediated suppression of lymphocyte responses in tuberculosis.
(Kleinhenz M, et al. J Clin. Invest.1981, 68:153-621.)

constituents:
• Alkamides (20+isobutylamides).
• Phenylpropanoids, (Caffeic acid esters).
• Flavonoids, (Rutoside).
• Polyacetylenes, (E. pallida only).
• High MW Polysaccharides (rhamnoarabinogalactan MW ca.450,00 +heteroxylan MW ca 35,000)
• Inulin, Volatile Oils, Trace amounts of Pyrrolizidine alkaloids, Phytosterols, sugars.
• Constituent profile varies between species and plant part (root, leaf, flower).

pharmacology:
• Immunostimulatory effects: Numerous studies show that Echinacea extracts stimulate nonspecific immunity, particularly phagocytosis of granulocytes. Polysaccharide fractions stimulate cytotoxic activity of macrophages, and enhance secretion of IL-1, IFNb, and TNFa as well as some proliferation of T cells. The polyacetylenes are mildly antibacterial against Streptococcal and Staphylococcal organisms. The immunostimulatory activity depends on the combined action of several constituents of the plant.
• Anti-inflammmatory effects: Echinacea extracts inhibit hyaluronidase, stimulate fibroblasts, inhibit the arachadonic cascade via inhibition of lipoxygenase and cyclooxygenase, and protect collagen from free radical induced damage. (Bauer R. Z Arztl Fortbild (Jena) 1996 Apr;90(2):111-115 ; Snow J. The Protocol Journal of Botanical Medicine, 1997 2,2:18-24).

clinical trials:
• topical: Wound healing and anti-inflammatory effects of topical Echinacea (Echinacin) were confirmed by Viehmann in a large (n=4598) population studied over a 5 month period, with an 85% success rate. Coeugniet found that adjuvant use of oral E.purpurea with a topical econazole cream improved recurrence rate of vaginal yeast infection from >60% to less than 17% compared with the econazole alone.
(Coeugniet E, Kuhnast R, Therapiewochie. 1986,36:3352-3358; Viehman P, Erfafrungsheilk, 1978,27:353-358.)

• colds and flu: E. purpurea extract at 180 drops daily relieved flu symptoms while 90 drops daily was only as effective as placebo in a double blinded study according to Braunig et al. In a controlled trial, Schoenberger observed that patients taking E. purpurea had lower frequency of cold or flu infection compared to placebo, and the severity of symptoms if infected was reduced compared to placebo.
(Braunig B, et al. Zeitschrift Phytotherapie.1992,13:13-17; Schoenberger D.Forum Immunol.1992, 8:2-12.)

• other: Lersch et al found that E. purpurea extended mean survival times in advanced colorectal cancer patients (post chemo/surgery) and led to increased tumor stabilization and even regression. A clinical trial with HIV+ patients, conducted by Berman et al, showed significant increase in NK cell activity with E.angustifolia at 1gm TID for 16 weeks. (Lersch C, et al. Cancer Invest 1992;10(5):343-348; Berman S, et al. Int Conf AIDS. 1998;12:582.)

commentary :
• Unresolved controversy over limitations of use for Echinacea. The limitations of use asserted for Echinacea spp. by some authorities, especially Commission E, are controversial because of the lack of supportive evidence for the suggested limitations. In general, the German view, represented by Commission E is cautious and conservative, for example, Commission E does not list Echinacea angustifolia root and herb as approved at all, presumably because it considers their efficacy has not been substantiated.
(Blumenthal M, et al. 1998)

• Autoimmune conditions: Opposing the use of Echinacea spp. in all autoimmune diseases is controversial since there are currently no reports in the medical literature or adverse reaction reports in the toxicological literature of Echinacea administration worsening auto-immune diseases. Professional herbalists regularly use Echinacea in a range of autoimmune conditions, particularly those where etiological factors include "leaky gut syndrome" and "molecular mimicry" by microorganisms such as Yersinia or Klebsiella. However, professional herbalists have also reported a few cases, particularly MS patients, where Echinacea administration has been associated with a worsening of flare-up symptoms. Supervision by practitioners experienced or qualified in the use of herbs is necessary for treatment of autoimmune conditions. The lack of any studies, including long term studies, should be noted.

• Tuberculosis: The Commission E contraindication of Echinacea spp. in tuberculosis is also speculative. In the 1800's the Eclectic and regular physicians used Echinacea to treat TB before the discovery of streptomycin and reported no adverse effects. There are clinical reports of successful use of Echinacea in tuberculosis, although these are not controlled clinical trials.
(Bergner P. 1997.)

• HIV: Finally, the contraindication of Echinacea in HIV patients is also speculative, based upon the elevation in vitro of TNFa titers by Echinacea extracts. TNFa has been associated with increased HIV replication and cachexia in AIDS patients. However the in vitro work was done with purified E. Purpurea polysaccharides injected into mice; human tests show that oral administration of Echinacea extracts does not increase TNFa. There is evidence to suggest that Echinacea enhances NK mediated anti HIV activity. while considerable anecdotal evidence also supports Echinacea use for both opportunistic infections and immune restorative activity in HIV+ patients.
(Berman S, et al. Int Conf AIDS. 1998;12:582; Elassier-Beile U, et al. J. Clin. Lab. Anal. 1996, 10(6):441-445.)

• Duration of use: A much repeated limitation of use, for example by Commission E, is that Echinacea spp. should be consumed for a maximum period of 8-10 weeks and even that prolonged use may actually become immunosuppressive. There is noevidence for this assertion. The one study that is cited in this regard has been extensively criticized by Bone. Some adverse reaction reports from Germany are however based upon short term responses to injected Echinacea extracts. Western clinical herbalists may use Echinacea as a component of a maintainenance protocol for chronically ill patients over a period of years. It is true however that Echinacea is possibly the most "overused" herb today by self-prescribers looking for a "fix" for immunodepression that is etiologically more likely associated with nutritional, toxicological and lifestyle considerations .
(For discussion see: Bergner P.1997 Ch 7; Bone K, Modern Phytotherapist. 1997.3(3):17-21;.)

• Adulteration: In 1986 Dr Bauer revealed that much of the Echinacea used for research, including that of his group, had been adulterated with Parthenium integrifolium (also known as Missouri Snakeroot). This accounted for many of the negative results in studies. (Bauer R, et al.1986.) In addition, it became clear that earlier workers, including the Eclectics, had confused E. pallida with E. angustifolia. The two have different constituents and activities but were only classified as different species in 1968. (Bradley P.1992.) Adulteration in commerce remains a problem due to the high price commanded by Echinacea. It is recommended that only certified organic material is purchased from reputable suppliers.
(Bauer R, et al. 1986; Bradley P.1992: 81-83.)




Interactions

herb affecting drug performance: Immuno-suppressive therapy: Cyclosporine

• mechanism: Echinacea may indirectly interfere with immuno-suppressive therapy with drugs such as cyclosporine. There is no direct evidence for this interaction which is therefore speculative. Echinacea use does not affect pharmacokinetics of immuno-suppressive drugs.

• herbal concern: Transplant patients should only use immuno-modulating herbs such as Echinacea spp. under qualified supervision.

herb affecting drug performance: Chemotherapy

• research: Lersch et al conducted studies of so-called immunotherapy looking at nonspecific immunostimulation using low doses of cyclophosphamide, thymus extract, and Echinacea purpurea extracts in patients with far advanced colorectal cancers: While the study was uncontrolled and the sample small encouraging results were obtained. Even though all the patients died the combination treatment appeared to enhance immune function and contribute to modestly extended lifespan in these patients with inoperable tumors. Researchers documented partial tumor regression in one subject and a stable disease in six other patients by abdominal ultrasound, decrease of the tumor markers and/or chest x-ray. Mean survival time was four months, two patients survived for more than eight months. Immunotherapy was well tolerated by all patients without side effects.
(Lersch C, et al. Cancer Invest 1992;10(5):343-348.)

• herbal concern: Individuals undergoing chemotherapy for cancer should consult their treating physician and/or a healthcare professional trained in herbal medicine about potential value of adding Echinacea to their regime before starting such supplementation.

herb affecting drug performance: Econazole

• research: The efficacy of econazole against recurrent candidiasis significantly improved when combined with oral or topical echinacea preparations. Additionally, researchers found that the combined therapy reduced the incidence of recurrent infections.
(Coeugniet EG, Kuhnast R. Therapiewoche 1986;36:3352-3358.)


general herbal concern: Autoimmune conditions (controversial)

• Opposing the use of Echinacea spp. in all autoimmune diseases is controversial since there are currently no reports in the medical literature or adverse reaction reports in the toxicological literature of Echinacea administration worsening auto-immune diseases. Professional herbalists regularly use Echinacea in a range of autoimmune conditions, particularly those where etiological factors include "leaky gut syndrome" and "molecular mimicry" by microorganisms such as Yersinia or Klebsiella. However, professional herbalists have also reported a few cases, particularly MS patients, where Echinacea administration has been associated with a worsening of flare-up symptoms. Supervision by practitioners experienced or qualified in the use of herbs is necessary for treatment of autoimmune conditions. The lack of any studies, including long term studies, should be noted. See commentary below.

commentary :
• Unresolved controversy over limitations of use for Echinacea. The limitations of use asserted for Echinacea spp. by some authorities, especially Commission E, are controversial because of the lack of supportive evidence for the suggested limitations. In general, the German view, represented by Commission E is cautious and conservative, for example, Commission E does not list Echinacea angustifolia root and herb as approved at all, presumably because it considers their efficacy has not been substantiated.
(Blumenthal M, et al. 1998)

• Tuberculosis: The Commission E contraindication of Echinacea spp. in tuberculosis is also speculative. In the 1800's the Eclectic and regular physicians used Echinacea to treat TB before the discovery of streptomycin and reported no adverse effects. There are clinical reports of successful use of Echinacea in tuberculosis, although these are not controlled clinical trials.
(Bergner P. 1997.)

• HIV: Finally, the contraindication of Echinacea in HIV patients is also speculative, based upon the elevation in vitro of TNFa titers by Echinacea extracts. TNFa has been associated with increased HIV replication and cachexia in AIDS patients. However the in vitro work was done with purified E. Purpurea polysaccharides injected into mice; human tests show that oral administration of Echinacea extracts does not increase TNFa. There is evidence to suggest that Echinacea enhances NK mediated anti HIV activity. while considerable anecdotal evidence also supports Echinacea use for both opportunistic infections and immune restorative activity in HIV+ patients.
(Berman S, et al. Int Conf AIDS. 1998;12:582; Elassier-Beile U, et al. J. Clin. Lab. Anal. 1996, 10(6):441-445.)

• Duration of use: A much repeated limitation of use, for example by Commission E, is that Echinacea spp. should be consumed for a maximum period of 8-10 weeks and even that prolonged use may actually become immunosuppressive. There is no evidence for this assertion. The one study that is cited in this regard has been extensively criticized by Bone. Some adverse reaction reports from Germany are however based upon short term responses to injected Echinacea extracts. Western clinical herbalists may use Echinacea as a component of a maintainenance protocol for chronically ill patients over a period of years. It is true however that Echinacea is possibly the most "overused" herb today by self-prescribers looking for a "fix" for immuno-depression that is etiologically more likely associated with nutritional, toxicological and lifestyle considerations .
(For discussion see: Bergner P. 1997, Ch 7; Bone K, Modern Phytotherapist. 1997.3(3):17-21;.)

• Adulteration: In 1986 Dr Bauer revealed that much of the Echinacea used for research, including that of his group, had been adulterated with Parthenium integrifolium (also known as Missouri Snakeroot). This accounted for many of the negative results in studies. (Bauer R, et al.1986.) In addition, it became clear that earlier workers, including the Eclectics, had confused E. pallida with E. angustifolia. The two have different constituents and activities but were only classified as different species in 1968. (Bradley P.1992.) Adulteration in commerce remains a problem due to the high price commanded by Echinacea. It is recommended that only certified organic material is purchased from reputable suppliers.
(Bauer R, et al. 1986; Bradley P.1992: 81-83.)

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.


References

Bauer R. [Echinacea drugs--effects and active ingredients]. Z Arztl Fortbild (Jena) 1996 Apr;90(2):111-115. (Review) [Article in German]
Abstract: Echinacea-containing drugs have to be classified according to the used plant species (Echinacea purpurea, E. pallida or E. angustifolia), the processed part of the plant (root, upper parts or whole plant), and the mode of processing. Significant pharmacological effects have been found in vitro and in vivo for the expressed juice of the upper parts of E. purpurea and for alcoholic extracts of the roots of E. pallida, E. angustifolia and E. purpurea. The activity is mainly directed towards the nonspecific cellular immune system. Several active constituents are discussed: polysaccharides, glycoproteins, caffeic acid derivatives (cichoric acid) and alkamides.

Bauer R, et al. Immunologically active sesquiterpene esters from Parthenium integrifolium an aldulterant of Echinacea purpurea. at Biologically Active Natural Products Symposium, Phytochemical Society of Europe, Lausanne, Switzerland, 3rd-5th Sept. 1986.

Bergner P.The Healing Power of Echinacea and Goldenseal. Rocklin, CA. Prima Publishing, 1997.

Berman S, et al. Dramatic increase in immune mediated HIV killing activity induced by Echinacea angustifolia. Int Conf AIDS. 1998;12:582 (abstract no. 32309).
Abstract: BACKGROUND: Potential eradication of HIV infection is highly likely to require both antiviral therapy as well as reconstitution of an effective immune response. In an in vitro study, E.a. induced a marked increase in natural killer (NK) cell activity against HIV-transfected cells, in both HIV(+) and HIV(-) individuals. We conducted an in vivo study of the effects of E.a. on immune system function in HIV(+) individuals. DESIGN: Double blinded placebo controlled crossover trial. All patients were on either a stable treatment regimen or no antiretrovirals for at least the previous 12 weeks; changes of therapy during the study were a basis for exclusion. Patients received placebo or E.a.@1 gm TID for 16 weeks, followed by a 4 week washout, then 16 additional weeks crossed over. HIV-1 vital loads, CD4 counts, and assays of NK mediated lysis of gp-120 transfected CEM or human herpes virus 6 (HHV-6) H9 cells were done every 4 weeks. Data were analyzed by ANOVA for repeated measurements. RESULTS: A total of 12 patients out of 61 enrolled have completed the study to date. At baseline, all had markedly suppressed killing activity against HIV transfected cells compared to 20 matched HIV (-) individuals, regardless of initial viral load (range < 400-9122 copies/ml) or CD4 count (range 45-4541/mm3, mean = 250) (p < 0.001). While receiving E.a., mean NK mediated HIV-specific killing activity increased from 3.7 +/- 3.5 lyric units (LU) to 23.1 +/- 11.7 LU (p < 0.001). After 16 weeks of placebo the killing activity was not significantly different from baseline (4.1 +/- 3.2 LU; p = NS). In six patients to date, a similar marked augmentation of killing of HHV-6 infected cells was induced by E.a. There were no reported side effects or abnormal laboratory findings during the study. CONCLUSION: Echinacea angustifolia at the dosage used in this study, induced a dramatic improvement in immune system function, as measured by a marked augmentation of NK mediated lysis of HIV-transfected cells. These effects were seen in 11/12 patients, even in those who were most immunosuppressed. This response may be an indication that in patients with HIV infection immune system reconstitution is possible and could be achieved utilizing this nontoxic, inexpensive agent.

Blumenthal M, Busse WR, Goldberg A, et al, eds. The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, MA: Integrative Medicine Communications, 1998.

Bodinet C, Willigmann I, Beuscher N, Host-Resistance Increasing Activity of Root Extracts from Echinacea Species. 1993 Planta Med, 59 (Suppl.):A672.

Bone K. Echinacea: When should it be used? Modern Phytotherapist. 1997.3(3):17-21.

Bradley PR, ed. British Herbal Compendium, vol 1. Bournemouth, Dorset, UK: British Herbal Medicine Association, 1992, 81-89.

Braunig B, et al. Echinacea purpurea root for strengthening the immune response in flu-like infections. Zeitschrift Phytotherapie.1992,13:13-17.

Bukovsky M, Vaverkova S, Kost'alova D. Immunomodulating activity of Echinacea gloriosa L., Echinacea angustifolia DC. and Rudbeckia speciosa Wenderoth ethanol-water extracts. Pol J Pharmacol 1995 Mar-Apr;47(2):175-177.
Abstract: The effect of the ethanol-water extracts of Echinacea gloriosa L., Echinacea angustifolia DC. and Rudbeckia speciosa Wenderoth on immunological system of inbred mice was investigated. The extract of the root of Rudbeckia speciosa had the highest immunostimulatory activity.

Burger RA, Torres AR, Warren RP, Caldwell VD, Hughes BG. Echinacea-induced cytokine production by human macrophages. Int J Immunopharmacol 1997 Jul;19(7):371-379.
Abstract: Echinacea purpurea, a plant originally used by native Americans to treat respiratory infections, was evaluated for its ability to stimulate the production of cytokines by normal human peripheral blood macrophages in vitro. Commercial preparations of echinacea fresh pressed juice and dried juice were tested at concentrations ranging from 10 micrograms/ml to 0.012 microgram/ml and compared to endotoxin stimulated and unstimulated controls. Cytokine production was measured by ELISA after 18 h of incubation for IL-1 and 36 and 72 h for TNF-alpha, IL-6, and IL-10. Macrophages cultured in concentrations of echinacea as low as 0.012 microgram/ml produced significantly higher levels of IL-1, TNF-alpha, IL-6 and IL-10 (P < 0.05) than unstimulated cells. The high levels of IL-1, TNF-alpha, and IL-10 induced by very low levels of echinacea are consistent with an immune activated antiviral effect. Echinacea induced lower levels of IL-6 in comparison to the other cytokines measured. These results demonstrate the immune stimulatory ability of the unpurified fresh pressed juice of Echinacea purpurea and offer some insight into the nature of the resulting immune response as compared to endotoxin.

Coeugniet E, Kuhnast R, Recurrent Candidiasis: Adjuvant immunotherapy, with different formulations of Echinacin. Therapiewochie. 1986,36:3352-3358.

De Smet PAGM et al. (eds.) Adverse Effects of Herbal Drugs 2,1993.Berlin: Springer-Verlag.

Elassier-Beile U, et al. Cytokine production in leukocyte cultures during therapy with Echinacea extract. J. Clin. Lab. Anal. 1996, 10(6):441-445.

Facino RM, Carini M, Aldini G, Saibene L, Pietta P, Mauri P. Echinacoside and caffeoyl conjugates protect collagen from free radical-induced degradation: a potential use of Echinacea extracts in the prevention of skin photodamage. Planta Med 1995 Dec;61(6):510-514.
Abstract: The protective effect of caffeoyl derivatives (echinacoside, chlorogenic acid, chicoric acid, cynarine, and caffeic acid, typical constituents of Echinacea species) on the free radical-induced degradation of Type III collagen has been investigated. The macromolecule was exposed to a flux of oxygen radicals (superoxide anion and hydroxyl radical) generated by the xanthine/xanthine oxidase/Fe2+/EDTA system and its degradation assessed qualitatively by SDS-PAGE and quantitatively as the amount of soluble peptides (according to the 4-hydroxyproline method) released from native collagen after oxidative stress. The SDS-PAGE pattern of native collagen is markedly modified by free radical attack, with formation of a great number of peptide fragments with molecular masses below 97 kDa: in the presence of microM concentrations of echinacoside, there is a complete recovery of the native profile. Collagen degradation was, in fact, dose-dependently inhibited by all the compounds, with the following order of potency: echinacoside approximately chicoric acid > cynarine approximately caffeic acid > chlorogenic acid, with IC50 ranging from 15 to 90 microM. These results indicate that this representative class of polyphenols of Echinacea species protects collagen from free radical damage through a scavenging effect on reactive oxygen species and/or C-, N-, S-centered secondary radicals, and provide an indication for the topical use of extracts from Echinacea species for the prevention/treatment of photodamage of the skin by UVA/UVB radiation, in which oxidative stress plays a crucial role.

Kleinhenz M E, Ellner J J, Spagnuolo P J, Daniel T M, Suppression of Lymphocyte Responses by Tuberculous Plasma and Mycobacterial Arabinogalactan. J Clin. Invest.1981, 68:153-621.

Lersch C, Zeuner M, Bauer A, Siemens M, Hart R, Drescher M, Fink U, Dancygier H, Classen M. Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea extracts (echinacin) in patients with far advanced colorectal cancers: preliminary results. Cancer Invest 1992;10(5):343-348.
Abstract: Outpatients (n = 15) with metastasizing far advanced colorectal cancers received immunotherapy consisting of low-dose cyclophosphamide (LDCY) 300 mg/m2 every 28 days i.v., thymostimulin 30 mg/m2, days 3-10 after low-dose cyclophosphamide i.m. once daily, then twice a week, and echinacin 60 mg/m2 together with thymostimulin i.m. All patients had had previous surgery and/or chemotherapy and had progressive disease upon entering the study. Two months after onset of therapy a partial tumor regression was documented in one and a stable disease in 6 other patients by abdominal ultrasonography, decrease of the tumor markers carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, and/or chest roentgenography, which may also be attributed to the natural course of disease. Mean survival time was 4 months, 2 patients survived for more than 8 months. Immunotherapy was well tolerated by all patients without side effects.

Luettig B, Steinmuller C, Gifford GE, Wagner H, Lohmann-Matthes ML. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Natl Cancer Inst 1989 May 3;81(9):669-675.
Abstract: In this study, acidic arabinogalactan, a highly purified polysaccharide from plant cell cultures of Echinacea purpurea, with a molecular weight of 75,000, was effective in activating macrophages to cytotoxicity against tumor cells and micro-organisms (Leishmania enriettii). Furthermore, this polysaccharide induced macrophages to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), and interferon-beta 2. Arabinogalactan did not activate B cells and did not induce T cells to produce interleukin-2, interferon-beta 2, or interferon-gamma, but it did induce a slight increase in T-cell proliferation. When injected ip, this agent stimulated macrophages, a finding that may have therapeutic implications in the defense against tumors and infectious diseases.

Melchart D, Linde K, Worku F, Sarkady L, Holzmann M, Jurcic K, Wagner H. Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea. J Altern Complement Med 1995 Summer;1(2):145-160.
Abstract: This article describes and discusses five placebo-controlled randomized studies investigating the immunomodulatory activity of preparations containing extracts of Echinacea in healthy volunteers. A total of 134 (18 female and 116 male) healthy volunteers between 18 and 40 years of age were studied. Two studies tested intravenous homeopathic complex preparations containing Echinacea angustifolia D1 (study 1) and D4 (study 5). Two studies (2 and 3a) tested oral alcoholic extracts of roots of E. purpurea, one study an extract of E. pallida roots (study 3b), and one study an extract of E. purpurea herb (study 4). Test and placebo preparations were applied for four (study 5) or five (studies 1-4) consecutive days. The primary outcome measure for immunomodulatory activity was the relative phagocytic activity of polymorphonuclear neutrophil granulocytes (PNG), measured in studies 1 and 2 with a microscopic method and in studies 3, 4, and 5 with two different cytometric methods. The secondary outcome measure was the number of leukocytes in peripheral venous blood. Safety was assessed by a screening program of blood and other objective parameters as well as by documentation of all subjective side effects. In studies 1 and 2 the phagocytic activity of PNG was significantly enhanced compared with placebo [maximal stimulation 22.7% (95% confidence interval 17.5-27.9%) and 54.0% (8.4-99.6%), respectively], while in the other studies no significant effects were observed. Analysis of intragroup differences revealed significant changes in phagocytic activity during the observation periods in five test and three control groups. Leukocyte number was not influenced significantly in any study. Side effects due to the test preparations could not be detected. Our studies provide evidence for immunomodulatory activity of the homeopathic combination tested in study 1 and the E. purpureae radix extract tested in study 2. The negative results of the other three studies are difficult to interpret due to the different methods for measuring phagocytosis, the relevant changes in phagocytic activity within most placebo and treatment groups during the observation period, and the small sample sizes. Future studies should be performed on patients rather than healthy volunteers and use standardized or chemically defined monopreparations of Echinacea.

Mengs U, Clare CB, Poiley JA. Toxicity of Echinacea purpurea. Acute, subacute and genotoxicity studies. Arzneimittelforschung 1991 Oct;41(10):1076-1081.
Abstract: Single oral or intravenous doses of the expressed juice of Echinacea purpurea (EP) proved virtually non-toxic to rats and mice. After 4 weeks of oral administration in doses amounting to many times the human therapeutic dose laboratory tests and necropsy findings gave no evidence of any toxic effects in rats. Tests for mutagenicity carried out in microorganisms and mammalian cells in vitro and in mice all gave negative results. In an in vitro carcinogenicity study EP did not produce malignant transformation in hamster embryo cells.

Mullins RJ. Echinacea-associated anaphylaxis. Med J Aust 1998 Feb 16;168 (4):170-171.
Abstract: A woman with atopy experienced anaphylaxis after taking, among other dietary supplements, a commercial extract of echinacea. Hypersensitivity was confirmed by skinprick and RAST testing. Regular ingestion of echinacea by up to 5% of surveyed patients with atopy, combined with detection of echinacea-binding IgE in atopic subjects (19% by skin testing; 20% with moderate to strong reactivity by RAST testing), raises the possibility of severe allergic reactions, even with first-time use, due to cross-reactivity with other structurally similar allergens. Patients with atopy should be cautioned about the risk of developing life-threatening reactions to complementary medicines, including echinacea.

See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology 1997 Jan;35(3):229-235.
Abstract: Extracts of Echinacea purpurea and Panax ginseng were evaluated for their capacity to stimulate cellular immune function by peripheral blood mononuclear cells (PBMC) from normal individuals and patients with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome. PBMC isolated on a Ficoll-hypaque density gradient were tested in the presence or absence of varying concentrations of each extract for natural killer (NK) cell activity versus K562 cells and antibody-dependent cellular cytotoxicity (ADCC) against human herpesvirus 6 infected H9 cells. Both echinacea and ginseng, at concentrations > or = 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups. Similarly, the addition of either herb significantly increased ADCC of PBMC from all subject groups. Thus, extracts of Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal individuals and patients with depressed cellular immunity.

Schoenberger D. The influence of immune stimulatintg effects of pressed juuice from Echinacea purpurea on the course and severity of colds. Forum Immunol.1992, 8:2-12.

Snow J. Echinacea spp. Monograph The Protocol Journal of Botanical Medicine, 1997 2,2:18-24.

Viehman P. Erfarungen mit einer echinacea haltigen hautsalbe. Erfafrungsheilk, 1978,27:353-358.

Wagner H, Jurcic K. [Immunologic studies of plant combination preparations. In-vitro and in-vivo studies on the stimulation of phagocytosis]. Arzneimittelforschung 1991 Oct;41(10):1072-1076. [Article in German]
Abstract: The activity of phagocytosis was tested in the in vitro granulocyte test and the in vivo carbon-clearance-test in the mouse for an extract combination consisting of four plant extracts (Echinacea angustifolia, Eupatorium perfoliatum, Baptisia tinctoria and Arnica montana). In both immune models, a step by step stimulation of the activity of phagocytosis by the addition of the four plant extracts was shown with an increase in effectiveness of partially over 50% in comparison to the pure Echinacea angustifolia mono-extract. The extract combination showed also in both test models a higher efficiency than two other differently composed combination preparations and two Echinacea mono-preparations.

Wildfeuer A, Mayerhofer D. [The effects of plant preparations on cellular functions in body defense]. Arzneimittelforschung 1994 Mar;44(3):361-366. [Article in German]
Abstract: Two preparations of Echinacea purpurea and a preparation of Eleutherococcus senticosus increased the in vitro phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30-45%. The chemotactic migration of granulocytes in the Boyden Chamber was increased by 45% with an Echinacea purpurea extract. The two herbal preparations had no effect in either direction on intracellular killing of bacteria or yeasts. Echinacea and Eleutherococcus preparations did not induce in vitro transformation of lymphocytes. The misteltoe preparation examined (Viscum album) did not influence the tested functions of granulocytes, monocytes or lymphocytes of healthy donors.