Scientific Name(s): Echinacea angustifolia DC, Echinacea pallida (Nutt.) Britton, Echinacea purpurea (L.) Moench Common Name(s): American coneflower, Black Sampson, Black Susan, Comb flower, Echinacea, Echinaceawurzel, Hedgehog, Igelkopfwurzel, Indian head, Kansas snakeroot, Narrow-leaved purple coneflower, Purple coneflower, Purpursonnenhutkraut, Racine d'echininacea, Radix Echinaceae, Rock-up-hat, Roter sonnenhut, Scurvy root, Snakeroot, Sonnenhutwurzel
Although evidence of efficacy in the treatment of infections is limited, use of echinacea as prophylaxis for upper respiratory tract infections has been reported. Use of echinacea for the treatment of anxiety and cancer has been investigated. Specific recommendations for use are unreliable due to variations in the composition of commercial products and inconsistent clinical trial results.
A major limitation of available dosing information is the lack of standardization of echinacea preparations. Commercial preparations contain echinacea components derived from different plant parts, species, and varieties. Recommended dosing includes the following: 300 mg of dry powdered extract (standardized to echinacoside 3.5%), 0.25 to 1.25 mL of liquid extract (1:1 in alcohol 45%), 1 to 2 mL of tincture (1:5 in alcohol 45%), 2 to 3 mL of expressed juice of E. purpurea, and 0.5 to 1 g of dried root or tea (all administered 3 times daily). Long-term use of echinacea or use for longer than 10 days in acute infections in otherwise healthy individuals is not recommended. Parenteral use is not recommended.
Avoid use with known hypersensitivity to plants of the Asteraceae/Compositae family. Echinacea is also contraindicated in patients with rheumatoid arthritis, systemic lupus erythematosus, leukosis, multiple sclerosis, tuberculosis, and HIV infection.
Information regarding safety and efficacy in pregnancy and lactation is lacking. Limited clinical evidence, expert opinion, and long-term traditional use suggest that oral echinacea use is safe during pregnancy at normal dosages. Echinacea should be used with caution during lactation.
Specific case reports of interactions are limited, although one report describes an interaction with etoposide. Data regarding echinacea effects on the cytochrome P450 (CYP-450) enzyme system are conflicting.
Adverse reactions with echinacea are rare. The most commonly reported reactions were allergy, GI upset, and rash. A case report of leukopenia, possibly caused by long-term echinacea use, has been published. Due to conflicting data, echinacea should not be used in any condition potentially affected by immune stimulation or suppression such as HIV, tuberculosis, multiple sclerosis, and immunosuppressive therapy. Use caution in patients with hepatic impairment.
There is little evidence regarding toxicity with echinacea, despite its widespread use. Echinacea has not been associated with acute or chronic toxic effects. Patients with hepatic impairment should use echinacea with caution, as case reports of hepatotoxicity exist.
Echinacea is a member of the Compositae family (also called the Asteraceae family), which is native to eastern and central North America. "Kansas snakeroot" or "snakeroot" should not be confused with white snakeroot (Ageratina altissima).1 There are at least 9 species of echinacea, with E. purpurea, E. pallida, and E. angustifolia most commonly used for medicinal purposes.1, 2 Because of the difficulty in identifying echinacea species, much of the early European research, particularly on E. angustifolia, may have actually been conducted on E. pallida.3
Echinacea species are perennial herbs that grow up to 1.2 m in height. The plant has narrow leaves and stout stems that blossom into large, solitary flower heads with lavender or purple florets and central rigid bracts. The traditional Radix Echinaceae preparation consists of the fresh or dried roots (either single taproots or fibrous roots) of E. angustifolia.3 When chewed, the root has a pungent taste and causes tingling of the lips and tongue.2, 3 Additional plant parts used include fresh or dried flowering tops and fresh pressed juice from the flowering tops of E. purpurea.
Echinacea is a popular herbal remedy in the United States. The plant was used in traditional medicine by American Indians and was quickly adopted by settlers. During the 1800s, claims for the curative properties of the plant ranged from blood purification to treatment of dizziness and rattlesnake bites. During the early 20th century, extracts of the plant were used as anti-infectives; however, 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 and internally to stimulate the immune system.2, 3, 4
The chemical constituents of echinacea are well described; biologically active constituents include a volatile oil (containing pentadecadiene, pentadecene, ketoalkynes, and ketoalkenes), alkamides (mainly a mixture of isobutylamides), polyalkenes, polyalkynes, caffeic acid derivatives, and polysaccharides.2, 3, 4, 5 It has been reported that the alkamides found in echinacea are available following oral administration, but that caffeic acid derivatives are not.4
Toxic pyrrolizidine alkaloids (isotussilagine and tussilagine) have also been identified at low levels.3, 6
Uses and Pharmacology
Methodological concerns, including variations in plant species, plant parts, preparations, and dosages, as well as high dropout rates and a lack of intention-to-treat analyses, make comparisons within individual clinical trials difficult.7, 8
Antihyaluronidase activity,9 inhibition of prostaglandins,10, 11 and reduction in proinflammatory mediators in vitro12 and in rodents have been demonstrated.13 When injected intravenously (IV) and applied topically, echinacea inhibited inflammation induced in rodents.14
No clinical data exist regarding the use of echinacea in the management of inflammatory conditions.
Root extracts from 3 echinacea species (E. purpurea, E. angustifolia, and E. pallida) produced concentration- and time-dependent induction of apoptosis in human pancreatic and colon cancer cell lines.15 In mice, the mean survival age was prolonged and thymic lymphoma enlargement suppressed with 8 weeks of echinacea therapy; other experiments demonstrated elevated natural killer cell levels and prolonged survival times in leukemic mice.16, 17 In a study in rats, coadministration of cadmium and echinacea led to significantly increased concentrations of cadmium in certain organs and in blood.18 In an in vitro study, typical constituents of echinacea species applied topically were effective in the prevention and/or treatment of skin damage caused by ultraviolet/ultraviolet B radiation. Another study suggested radioprotection following oral administration of echinacea.20
In a trial investigating the effects of an IV-administered polysaccharide fraction of echinacea among 15 patients with advanced gastric cancer, increases in median number of leukocytes occurred; however, the differences were not considered clinically relevant.21 Another study involving 23 patients with tumors showed no effect on cytokine or leukocytes after use of an E. angustifolia preparation.22
Anxiolytic activity of echinacea has been demonstrated in limited animal studies.23, 24, 25
An open-label study investigated anxiolytic activity of E. angustifolia extract in healthy individuals (n = 33) with elevated anxiety scores. The study did not include a placebo group, and participants were randomized to 1 or 2 capsules (each capsule containing 20 mg of extract) daily for 1 week. Only the higher dose resulted in a reduction in anxiety scores during treatment and for 2 weeks afterward.26 The observed effect may be due to lipophilic alkylamide constituents interacting with cannabinoid receptors.23
Many studies investigating the immunomodulatory properties of various echinacea species, extracts, and plant parts have been conducted. Reviews of the literature generally agree that echinacea extracts exert effects on markers of the immune system.4, 27 In vivo animal studies with negative findings have also been published. In vitro and animal studies are ongoing.28, 29
Clinical studies have been conducted largely in healthy adults10, 30, 31, 32, 33, 34, 35 or to investigate echinacea's potential in preventing or treating specific infections (see Infections/Antimicrobial Effects section).4, 27 Effects such as enhanced macrophage function, stimulation of cytokine production (including certain interleukins and tumor necrosis factor alpha), enhanced natural killer cell function, and increased mean circulating total white blood cell counts have been demonstrated; however, the impact of these effects on clinical outcomes has not been established.4, 27, 36 Reviews note that overt stimulation of immune functions is not without potential for harm4, 27; a case report of potential activation of autoimmune disease (Sjogren syndrome) with echinacea use exists.37
Antifungal, antibacterial, and antiviral (herpes simplex virus, HIV, and influenza) properties have been studied in vitro4, 38, 39, 40, 41; however, widespread traditional use of echinacea for infections, especially for the common cold, and the availability of clinical trial data make animal data mostly irrelevant.7
According to a Cochrane review of quality clinical trials (conducted up to mid 2013) evaluating echinacea products in the treatment of upper respiratory tract infections, only 1 of 7 studies showed a reduction in duration of infection.7 A pooled analysis was not conducted due to the strong clinical heterogeneity of the studies, which made definitive statements about effects difficult.7, 42 In a clinical trial investigating the effect of echinacea on the severity and recurrence of genital herpes, no difference was observed when compared with placebo.43 A placebo effect was reported in a clinical study using echinacea for treating upper respiratory tract infections,44 and another clinical study suggested an increased risk of disease in echinacea-treated children with otitis media.45
Published reviews of echinacea for infection prevention should be considered separately from those evaluating its role in infection treatment, as prophylactic administration occurs prior to symptom onset and for a longer duration.7, 46 A Cochrane review of quality clinical trials (N = 4,631), including trials published up to mid 2013, evaluating echinacea products in the prevention of upper respiratory tract infections showed a nonsignificant trend in favor of echinacea as prophylaxis; however, the effect size was of limited clinical relevance (10% to 20% relative risk [RR] reduction).7 In a meta-analysis of 6 clinical studies (N = 2,458 patients), 4 evaluating echinacea and 2 evaluating other supplements, the risk for recurrent respiratory infections was reduced with echinacea (RR, 0.649; 95% confidence interval [CI], 0.545 to 0.774; P < 0.0001).46
The literature includes limited studies evaluating the effects of echinacea on exercise enhancement in animals; however, studies demonstrating anti-inflammatory and antioxidant effects of echinacea have led to supplementation of horse feeds with echinacea products.47
Studies in athletes did not demonstrate enhanced performance or change in hemoglobin concentration with echinacea 8,000 mg daily over 6 weeks.48, 49, 50
According to a consensus statement, there is a lack of evidence supporting use of echinacea in athletes to maintain immune health.36
Chicoric acid extracted from E. purpurea was protective against alcohol-induced hepatic steatosis in mice.51
Extracts of the flowering parts of echinacea demonstrated antitussive and bronchodilatory effects in rodents.52
Effects on adipogenesis occurred in vitro, suggesting that extracts of echinacea may have a role in treating obesity or diabetes.53
A major limitation reported in meta-analyses of available trial data was the lack of standardization of echinacea preparations. Many products lacked active echinacea chemical compounds or were contaminated with other chemical entities.4, 7
Recommended dosing includes the following: 300 mg of dry powdered extract (standardized to echinacoside 3.5%), 0.25 to 1.25 mL of liquid extract (1:1 in alcohol 45%), 1 to 2 mL of tincture (1:5 in alcohol 45%), 2 to 3 mL of expressed juice of E. purpurea, and 0.5 to 1 g of dried root or tea (all administered 3 times daily).36 Safety and tolerability have been studied in children with equivocal results.45, 54, 55
Parenteral use is not recommended due to a lack of evidence of safety or effectiveness.7, 21
Long-term use or use for longer than 10 days in acute infections in otherwise healthy individuals is not recommended.56
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
A prospective cohort study (N = 206) demonstrated no increased risk of fetal malformations with the use of echinacea during the first trimester57; however, the study was limited by small sample size, allowance of detection of common malformations only, and lack of standardization of preparations.4, 58
Evidence regarding safety of echinacea use during lactation is lacking; a case report documented breast milk concentrations that were similar to serum levels 1 to 4 hours after consumption.59, 60
Despite the Complete German Commission E Compendium Monographs statement that oral echinacea is safe for use during lactation at recommended dosages,61 echinacea should be used with caution during lactation.59, 60, 62
Data regarding effects on the CYP-450 enzyme system are conflicting.63, 64, 65, 66
In 2 small studies, no impact of echinacea on docetaxel67 or etravirine68 pharmacokinetics was found; however, a case report describes an interaction with etoposide.69 Due to upregulation of CYP1A2 (caffeine) and CYP3A4 (midazolam), effects on therapeutic agents such as amitriptyline, haloperidol and olanzapine, theophylline, zileuton, efavirenz and nevirapine, tamoxifen, and etoposide have been suggested.70, 71 Echinacea was less active in inhibiting CYP2C8 enzyme activity (metabolism of antihyperglycemic agents) than were 2 of the other 6 plants tested (ie, cranberry and saw palmetto).72
Clozapine: CYP3A4 inducers (weak) may decrease the serum concentration of clozapine. Monitor therapy.83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93
Etoposide: Echinacea may increase the serum concentration of etoposide. Monitor therapy.94, 95, 96, 97, 98, 99
Etoposide phosphate: Echinacea may increase the serum concentration of etoposide phosphate. Monitor therapy.94, 95, 96, 97, 98, 99
Immunosuppressants: Echinacea may diminish the therapeutic effect of immunosuppressants. Consider therapy modification.100, 101
Nimodipine: CYP3A4 inducers (weak) may decrease the serum concentration of mimodipine. Monitor therapy.102, 103
In reviews and meta-analyses of clinical trials of echinacea in the treatment and prevention of the common cold, allergic reactions, facial edema, and mild transient GI complaints were reportedly the most relevant.7, 46, 81 In trials evaluating echinacea for treatment of the common cold, equal dropout rates due to adverse events were reported for control and treatment arms, whereas in prevention studies, there was a trend toward higher dropout rates due to adverse effects in the treatment arm.7
Echinacea should be used with caution in individuals with hypersensitivity to ragweed, chrysanthemum, marigold, daisies, or related allergens.4, 73, 74
A case report of leukopenia, possibly caused by long-term use of echinacea, has been published.75
Debate exists regarding echinacea use in patients with autoimmune disorders. Until this issue is clarified, echinacea should not be used in any condition potentially affected by immune stimulation or suppression such as HIV, tuberculosis, multiple sclerosis, and immunosuppressive therapy.4, 76 One case report describes potential activation of autoimmune disease (Sjogren syndrome) with echinacea use.37
Patients with hepatic impairment should use echinacea with caution.76 Acute cholestatic hepatitis likely associated with echinacea root tablets (600 mg/day × 5 days) was reported in a 44-year-old healthy Greek male; possible product adulteration was not evaluated.82 In a study of patients with advanced gastric cancer, an association between use of IV E. purpurea extract and the deaths of 2 patients could not be eliminated.21
There is little evidence regarding toxicity with echinacea, despite its widespread use. Echinacea has not been associated with acute or chronic toxic effects.4
Despite low levels of pyrrolizidine alkaloids in echinacea,3, 6 limited case reports describe acute cholestatic hepatitis related to supplementation with echinacea in adults,77, 78 and acute liver failure in a child after 2 weeks of supplementation (total daily echinacea dose of 100.7 mg/day).79 Patients with hepatic impairment should use echinacea with caution.
High-dose oral and IV administration (ie, several times the standard human therapeutic dose) of the expressed juice of E. purpurea to rodents for 4 weeks produced no short-term, genotoxic, carcinogenic, mutagenic, or other toxic reactions.80 However, an association between use of IV E. purpurea extract and the deaths of 2 patients with advanced gastric cancer could not be eliminated.21
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