Facts & Comparisons > Echinacea

Echinacea

Scientific Name(s): Echinacea angustifolia DC. The related species E. purpurea (L.) Moench and E. pallida (Nutt.) Britton have also been used in traditional medicine. Family: Asteraceae (sunflowers)

Common Name(s): American coneflower , black susans , comb flower , echinacea , hedgehog , Indian head , Kansas snakeroot , narrow-leaved purple coneflower , purple coneflower , scurvy root , snakeroot

Clinical Overview

Uses of Echinacea

There is some evidence that echinacea ( E. purpurea and E. pallida ) is effective in shortening the duration of symptoms of URIs, including the common cold, but it has not been shown to be effective as a preventative. The variation in available products makes specific recommendations difficult to determine.

Echinacea Dosing

Echinacea clinical trials for prevention or treatment of cold symptoms have been run primarily on the fresh pressed juice of the herb, which is preserved with 22% alcohol. Typical daily doses are 5 to 10 mL of the juice. Echinacin ( Madaus , EC31) and Echinagard are fresh juice prepared from the herb. Extracts of the root are available, including Echinaforce and Echinacea Plus . These have been given at doses corresponding to 1 g of the crude herb or root 3 times/day. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9

Contraindications

Childhood, chronic diseases such as diabetes, bronchial asthma, allergy, or autoimmune deficiency, tuberculosis, leukemia, collagenous disease, multiple sclerosis, polyarthritis, HIV infection, organ transplantation, pneumonia, or fungal infections, other infections not involving the respiratory tract, known inflammatory GI disease or impairment of resorption, acute influenza, chronic diseases of the respiratory tract; patients taking any immunosuppressants including corticosteroids, antibiotics, or cytostatic therapy; pregnancy or lactation; fever; hypersensitivity to plants of the Asteraceae/Compositae family; and any type of acute infection. 1 , 2 , 3 , 4 , 5 , 10 , 11 , 12

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Best avoided during pregnancy, but a small prospective cohort study found no increased risk for malformations or other adverse outcomes. 13

Echinacea Interactions

None well documented.

Echinacea Adverse Reactions

Side effects are rare. Patients with allergies, specifically allergies to daisy-type plants (Asteraceae family) might be more susceptible to reactions. Nausea and other mild GI effects have been reported in clinical trials. Because of the potential immune stimulating property of echinacea, patients who are immunocompromised should not take echinacea. Many patients were excluded from clinical trials (see Pharmacology, Clinical Trials, Toxicology).

Toxicology

Little is known about the toxicity of echinacea.

Botany

There are at least 9 species of echinacea. The ones most commonly studied are E. purpurea , E. pallida , and E. angustifolia . 14

Echinacea is native to Kansas, Nebraska, and Missouri. There has been confusion regarding the identification of echinacea. Because of this confusion, it should be recognized that much of the early research conducted on this plant (in particular with European E. angustifolia ) was probably conducted on E. pallida . 15 At least 6 synonyms have been documented for these plants.

E. angustifolia is a perennial herb with narrow leaves and a stout stem that grows to 90 cm in height. The plant terminates in a single, colorful flower head. The plant imparts a pungent, acrid taste when chewed and causes tingling of the lips and tongue.

Echinacea products have been found to be adulterated with another member of the family Compositae, Parthenium integrifolium L. This plant has no pharmacologic activity.

History

Echinacea is a popular herbal remedy in the central US, an area to which it is indigenous. The plant was used in traditional medicine by the American Indians and quickly adopted by the settlers. During the 1800s, claims for the curative properties of the plant ranged from a blood purifier to a treatment for dizziness and rattlesnake bites. 16 During the early part of the 20th century, extracts of the plant were used as anti-infectives; however, the use of these products fell out of favor after the discovery of modern antibiotics.

The plant and its extracts continue to be used topically for wound-healing action and internally to stimulate the immune system. Most of the research during the past 10 years has focused on the immunostimulant properties of this plant.

Chemistry

Echinacea contains about 0.1% echinacoside, a caffeic acid glycoside. The pungent component of the plant is echinacein, a isobutylamide. 17 This compound is toxic to adult houseflies. The plant also contains a complex mixture of components that are now being elucidated. Depending on the species, the essential oil obtained from the root may be high in unsaturated alkyl ketones or isobutylamides. 15 Fresh aerial portions of echinacea contain a highly volatile germacrene alcohol that is not usually identified in dried plant material. 18 In addition, a number of alkamides have been found in the lipophilic fraction of E. angustifolia and E. purpurea roots. 19

Echinacea Uses and Pharmacology

A small but growing body of evidence is developing to support the traditional uses of echinacea as a wound-healing agent and immunostimulant.

Most studies have indicated that the lipophilic fraction of the root and leaves contains the most potent immunostimulating components. Although a number of pharmacologically active components have been isolated, no single compound appears to be responsible for the plant's activity. Polyunsaturated alkamides from E. angustifolia have been shown to inhibit in vitro the activity of sheep cyclooxygenase and porcine 5-lipoxygenase assays. 20

Treatment of the common cold
Animal data

Research reveals no animal data regarding the use of echinacea for treatment of the common cold.

Clinical data

Nineteen German controlled clinical trials examined the efficacy of 7 different echinacea preparations, alone or in combination, for the prevention or treatment of upper respiratory tract infections (URIs) including the common cold. The authors rated the overall quality of the studies, with a median score of 37% and a range of 7% to 70%. 21 These results correspond to the average scores (38.5%) found for other clinical trials in journals from 1990. 22 The authors of this review determined that the studies available as of 1993 revealed that echinacea may have an effect on the immune system, but that there is insufficient evidence to provide specific recommendations. 21

Barrett and colleagues published an evidence-based clinical review of echinacea in 1999. They examined 13 trials, 9 of which were reviewed by Melchart in 1994, and 4 additional studies (1 unpublished report). Barrett et al, found conclusions similar to those of Melchart in that there is some evidence that echinacea is effective for treatment, not for the prevention of URIs, but there is still a lack of definitive information to provide specific recommendations. 23 Brinkeborn and colleagues reported that patients receiving a commercially available echinacea product in Germany with 7 mg, 95% herb, and 5% root or a concentrate with 48 mg of the same crude extract, had a 50% reduction in 12 cold symptoms as judged by the patient and 60% as judged by physicians compared with placebo (see Table 1 for description of clinical trials). In addition, approximately 70% of physicians and 80% of patients judged the treatment to be effective. There was no information on whether echinacea decreased the duration of a cold. The authors did not speculate as to why it was effective while the fresh plant preparation was not. 1 Degenring provided information concerning an open-label, “adjunctive treatment” (term not described) trial in 77 patients receiving echinacea. Results showed that 72% of patients became symptom-free within 14 days. However, without a placebo control, it is impossible to determine if patients would have improved without treatment. 10 Dorn and colleagues used an unidentified E. pallida radix extract 900 mg/day in an unspecified divided dose regimen for 8 to 10 days to determine its effect on both viral and bacterial infections compared with a placebo. E. pallida decreased the length of the illness from 13 to 9.8 days compared with placebo for bacterial infections and 12.9 days to 9.1 days for viral infections ( P < 0.0001). 11

Another study used a commercially available echinacea product in Germany. Results showed a direct correlation to time of administration with patients taking the medication during the early phase (“...identified by the course of an indicator symptom during the first three days of observation”) showing faster improvement than those who started echinacea later. In the treatment group, 55.3% had greater than or equal to 50% improvement in global score compared with 27.3% in the placebo group. 2 Hoheisel and colleagues demonstrated that another commercially available product in Germany was more effective in shortening the duration of a cold and required treatment of a cold than placebo using subjective measures such as “Did you have a ‘real cold'?” (fully expressed symptoms of acute respiratory tract infection). Although more patients experienced a “real cold” with placebo than echinacea, the severity of symptoms were similar in the 2 groups. 3 Thom and colleagues used a commercially available E. pallida root extract combination product (Kanjang mixture) in Scandinavia. Compared to placebo, the Kanjang mixture caused a decrease in subjective symptoms such as degree and frequency of cough, quality of sleep, efficacy of mucus discharge, nasal congestion, and global evaluation compared with placebo. These improvements were noted as early as 2 days after initiation of treatment and were more prominent at day 4. Patients took the echinacea treatment for an average of 5.2 days vs 9.2 days for placebo. No side effects were reported in either group; however, 2 patients discontinued the active treatment because they could not tolerate the taste of the medication. 12

There were several limitations of the studies listed in Table 1. Only 2 studies measured patient compliance and 3 studies addressed concomitant medication use that might affect cold symptoms. 1 , 2 , 12 Inclusion and exclusion criteria were not always provided, and if provided, they were poorly defined. Four studies mentioned that the placebo product was similar to the echinacea preparation to help ensure blinding. However, one of these studies reported that the treatments “...could almost not be distinguished from one other by their smell or taste.” However, Melchart mentioned that “because of the characteristic taste of echinacea extracts it is almost impossible to prepare a completely indistinguishable placebo.” 1 , 2 , 4 None of the studies asked patients if they had tried an echinacea product before. If so, what kind was it and did it work? The methods for randomization and verification were not provided. The studies used subjective measures of a cold that can be highly variable from patient to patient, and the methods for measuring these subjective outcomes varied greatly. Some of the studies used plant parts ( purpurea root) that are not approved by The German Commission E because they lack documentation pertaining to efficacy. There were 6 different preparations (extract vs. tab vs squeezed sap vs combination product), 2 different species ( E. purpurea or pallida ), and 6 different doses used in the 6 studies. None of the studies tested the products for quality testing procedures currently available or standardized the products prior to initiation of the study. 24 Two of the studies used patients who were more prone to the common cold. 1 , 3 One of the studies lacked a placebo control, which makes it virtually impossible to reach a conclusion regarding efficacy. 10 The exact time of initiation of echinacea treatment was not well defined in the studies. Some mentioned echinacea was taken at the first sign of a cold, others did not mention when therapy was initiated.

Table 1: English–Language Studies of Echinacea for the Treatment of the Common Cold Study & country N Study design Species Formulation Dose Outcome Side effects Brinkeborn (1999) Sweden 246 R, D-B, P-C, intent-to-treat, healthy volunteers “prone to common cold” E. purpurea (1) Echinaforce (6.78 mg, 95% herb, and 5% root) or (2) Echinaforce concentrate (48.27 mg of the same crude extract) or (3) special E. purpurea extract preparation (29.6 mg crude extract based on root only). 2 tabs tid at the first sign of a cold for ≤ 7 days or until pt felt better Echinaforce and the concentrate were more effective at relieving 12 symptoms of the common cold compared with special Echinacea extract and placebo. Similar to placebo. Most common was GI upset. Degenring (1995) Austria 77 Open-label, 4-week observation E. purpurea Echinaforce (6.78 mg, 95% herb, and 5% root) “made from stems and leaves, together with the root.” Alcohol content, 57%. 30 drops tid × 14 days at the first sign of a cold; ≤ 3 days after 88.2% of pts and 86.8% of physicians rated echinacea to have clinically relevant efficacy (very good, good, or satisfactory). 76 pts and physicians rated tolerability as good. One pt dc'd therapy due to SEs. Dorn (1997) Germany 160 R, D-B, P-C, single-center E. pallida Liquid form of E. pallida radix extract. 90 drops (900 mg) in divided doses for 8 to 10 days Length of illness, overall symptom scores, and whole clinical scores were decreased compared with placebo. None mentioned. Henneicke-von Zepelin (1999) Germany 259 R, D-B, P-C, multi-center, intent-to-treat E. purpurea , E. pallida Esberitox N tablets (ethanolic-aqueous extracts of 2 mg of herba thujae occidentalis , 7.5 mg of radix echinaceae [ purpureae + pallidae = 1+1], 10 mg radix baptiaiae tinctorae , plus other ingredients). “3 tabs tid for 7 to 9 days, and at least until the final visit to the investigator” Esberitox N was more effective in relieving 18 cold symptoms than placebo. Mean time to response was 4.8 days in the echinacea group vs 7 days in the placebo group. Similar to placebo. Hoheisel (1997) Sweden 120 R, D-B, P-C, intent-to-treat, healthy volunteers with history of recurrent URIs. E. purpurea Echinagard (“squeezed sap of the herb”). 20 drops q 2 hrs for the first day, at the first sign of URI then tid for ≤ 10 days 60% of placebo and 40% of echinacea pts experienced a “real” cold, with faster improvement time by 4 to 5 days. Pts stopped treatment median 6 days on echinacea vs 10 on placebo. None reported. Thom (1997) Norway 60 R, D-B, P-C pts with the common cold E. pallida Kanjang mixture with E. pallidia radix 10 g/100 mL mixed with 4 other “active ingredients.” 15 mL tid for 5 to 10 days Kanjang mixture improved symptoms compared with placebo on days 2 and 4. None reported.

R = randomized; D-B = double-blind; P-C = placebo-controlled; pt = patients.

Severity of illness, runny nose and sneezing, tearing/burning eyes, sore throat, headache, dizziness, weakness, drowsiness, muscle pain, limb pain, fever, cough, blocked nose, earache, or any other complaint most probably related to the cold.

Prevention of the common cold
Animal data

Research reveals no animal data regarding the use of echinacea for prevention of the common cold.

Clinical data

Three clinical trials, 2 were randomized, double-blind, placebo-controlled English-language trials, and 1 placebo-controlled have been conducted that examined the effectiveness of echinacea in the prevention of the common cold and other URIs (see Table 2). None of the studies found echinacea to be effective. However, 1 study did not calculate power (ie, the ability of a study to find a significant difference, if in fact, one exists). One calculated the study power at only 20% and the other 75%, suggesting that neither study probably enrolled enough subjects. 4 , 5 , 25 Melchart and colleagues commented that echinacea may cause a 10% to 20% relative risk reduction for the occurrence of a cold; however, larger sample sizes than those used would be required to prove this theory. 4 As with the treatment trials, 2 of the studies determined whether the placebo was a true placebo. 4 , 5 The other study questioned whether patients thought they were receiving a placebo, and the investigators found no significant difference between groups. However, the dosage form used in this study was not described. Only 1 of the studies tested the products for quality. 25 However, the study did not list the species they used or if the product contained the desired components. None of the studies standardized their products prior to initiation of the study. 24 Melchart and colleagues reported that 45% of the subjects had tried echinacea before, which could have affected the results. This study also used an echinacea species ( E. angustifolia ) and plant parts ( E. purpurea root) that are not approved by The German Commission E because they lack documentation of efficacy. 4

Table 2: English-Language Studies of Echinacea for Prevention of the Common Cold Study & country N Study design Species Formulation Dose Outcome Side effects Grimm (1999) Germany 108 R, D-B, P-C, pts with a history of cold > 3x/yr E. purpurea Echinacin-Liquidum made from fresh expressed juice of whole flowering plants of Echinacea purpurea (verum) harvested without its roots with 22% alcohol. 4 mL bid for 8 weeks No difference in occurrence, severity, or duration. Similar to placebo. Melchart (1998) Germany 289 R, D-B, P-C E. purpurea , E. angustifolia Ethanolic extracts (plant ratio 1:11 in 30% alcohol) from the roots of E. angustifolia or E. purpurea . 50 drops bid, M-F × 12 weeks Not an effective preventative. Similar to placebo. Turner (2000) USA 92 P-C, experimental rhinovirus Possibly E. pallida , E. angustifolia but not directly stated 0.16% cichoric acid with almost no echinacosides or alkamides. 300 mg tid × 14 days prior to virus challenge Not an effective preventative. Similar to placebo.

R = randomized; D-B = double-blind; P-C = placebo-controlled; pt = patients.

Other uses

When injected IV in mice or rats, echinacea extract almost completely inhibited carrageenan-induced mice or rat paw edema. Similarly, when the extract was applied topically, it inhibited almost completely the inflammation induced by croton oil applied to the mice or rats' ear. 26 Its activity was slightly less than that of topical indomethacin. The most active anti-inflammatory compound(s) has a molecular weight of between 30,000 and 100,000. 27

Several caffeoyl conjugates have been isolated from E. angustifolia that demonstrate antihyaluronidase activity; these include chicoric acid, cynarine, chlorogenic acid, and caftaric acid. 28 The inhibition of this enzyme is believed to limit the progression of certain degenerative inflammatory diseases.

Perhaps the most intriguing activity of this plant rests in the ability of its extracts to enhance the immune response. A number of in vitro and animal studies have documented the activation of immunologic activity. These extracts appear to exert their effects by stimulating phagocytosis, increasing cellular respiratory activity, and increasing the mobility of leucocytes. When ethanolic extracts were administered orally to rats, phagocytosis was enhanced. The lipophilic fraction was more active than the polar fraction. 29

The purified polysaccharide arabinogalactan, isolated from E. purpurea , was effective in activating macrophages to cytotoxicity against tumor cells and microorganisms following intraperitoneal injection in mice. 30 Arabinogalactan induces macrophages to produce tumor necrosis factor, interleukin-1, and interferon beta-2. Polysaccharides derived from E. purpurea enhance the cytotoxic activity of treated macrophages against tumor cells and the intracellular parasite Leishmania enrietti . 31 The research suggests that this activity may be of clinical value in the defense against tumors and infectious diseases, particularly in immunocompromised patients. However, a study involving 23 patients with tumors showed that an echinacea complex made with E. angustifolia had no effect on cytokine or leukocytes. 32

Dietary supplementation with E. purpurea to rats who were undergoing experimental irradiation resulted in the mobilization and enhancement of vitamin E-mediated oxidation/reduction pathways, suggesting that echinacea could have potential as a radioprotector. 33

One study found the administration of echinacea extracts to humans stimulated cell-mediated immunity following a single dose, but that repeated daily doses suppressed the immune response. 34 In a more recent German study conducted in a small number of patients (15) with advanced metastasized colorectal cancer, echinacin (a component of the plant) was added to treatment consisting of cyclophosphamide and thymostimulin; the mean survival time was 4 months, and two patients survived for more than 8 months, suggesting that this form of immunotherapy may have some value in treating these ill patients. 35

Although the results are encouraging, they are too preliminary to draw conclusions about the appropriate therapeutic uses of echinacea extracts. Similarly, there are no well-controlled studies that have evaluated the effects of OTC echinacea supplements. Consequently, dosages are not well defined.

An in vitro study demonstrated that typical constituents of echinacea species applied topically were effective in prevention/treatment of photo damage of the skin caused by UV/UVB radiation. 36

Dosage

Echinacea clinical trials for prevention or treatment of cold symptoms have been run primarily on the fresh pressed juice of the herb, which is preserved with 22% alcohol. Typical daily doses are 5 to 10 mL of the juice. Echinacin ( Madaus , EC31) and Echinagard are fresh juice prepared from the herb. Extracts of the root are available, including Echinaforce and Echinacea Plus . These have been given at doses corresponding to 1 g of the crude herb or root 3 times/day. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Best avoided during pregnancy, but a small prospective cohort study found no increased risk for malformations or other adverse outcomes. 13

Interactions

None well documented.

Adverse Reactions

Most of the contraindications and some of the possible side effects are theoretical and are not derived from actual case reports or studies of oral echinacea. According to The German Commission E, Echinacea purpurea and pallida , when taken orally, do not cause any side effects. 37 Parnham and colleagues reported results from an unpublished practice study to determine adverse effects and safety of the squeezed sap of E. purpurea . A total of 1231 patients with relapsing respiratory and urinary infections given echinacea for 4 to 6 weeks demonstrated the following side effects: Unpleasant taste (1.7%); nausea or vomiting (0.48%); abdominal pain, diarrhea, sore throat (0.24%). The authors reported that 90% of patients took the medication as directed. Parenteral administration was associated with immunostimulating-type reactions such as shivering, fever, and muscle weakness. 38 Degenring reported that 1 out of 77 patients who received the 6.78 mg, 95% herb, and 5% root formulation experienced nausea, restlessness, and aggravation of cold symptoms 4 days after starting the medication. 10 The symptoms were severe enough to require discontinuation of therapy. Other side effects reported in clinical trials were primarily GI in nature, such as mild nausea. 1 , 2 , 5 , 10 At the American Academy of Allergy, Asthma and Immunology 2000 annual meeting, 23 unpublished cases (2 “certain,” 10 “probable,” and 11 “possible”) of allergic reaction to echinacea consistent with IgE-mediated hypersensitivity were reported. Of the 23 cases, 34% were atopic, 13% were nonatopic, and 44% did not provide this information. Of another 100 atopic patients who had never taken echinacea, 20% had positive skin test reactions to echinacea, indicating a hypersensitivity without prior exposure to echinacea. 39 There was also a case of anaphylaxis caused by a combination echinacea product ( E. angustifolia and E. purpurea ) with other dietary supplements. The amount of echinacea product consumed was approximately double that recommended by the manufacturer. The patient had a high incidence of allergies to other substances. Of an additional 84 patients with asthma or allergic rhinitis, 16 subjects (19%) reacted to an echinacea skin prick. Only 2 patients had prior exposure to echinacea. 40

Toxicology

Little is known about the toxicity of echinacea despite its widespread use in many countries. It has been documented in American traditional medicine for more than a century and generally has not been associated with acute or chronic toxicity. Purified echinacea polysaccharide is relatively nontoxic. Acute toxicity studies found that doses of arabinogalactan as high as 4 g/kg injected intraperitoneally or IV were essentially devoid of toxic effects. 30

High-dose oral and IV administration (ie, several times the normal human therapeutic dose) of the expressed juice of E. purpurea to rodents for 4 weeks demonstrated no acute, subacute, genotoxic, carcinogenic, mutagenic, or other toxic reactions. 41

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