INTRODUCTION — Echinacea species are commonly referred to as coneflowers, a group of native American wildflowers from the daisy family (Asteraceae/Compositae) (picture 1) [1]. Echinacea is indigenous to North America and was used by Native Americans of the Great Plains. Samples of echinacea have been found in archeological digs from the 1600s, thought to be the location of Lakota Sioux village sites [2]. Native Americans used echinacea both topically and systemically for ailments such as burns, snakebites, pain, cough, and sore throat [3].
This topic will review the proposed clinical pharmacology of echinacea and clinical evidence addressing its efficacy, as well as precautions and contraindications to its use. A general discussion of herbal medications can be found elsewhere. (See "Overview of herbal medicine and dietary supplements".)
EPIDEMIOLOGY — Echinacea is generally used with the intention of treating or preventing uncomplicated upper respiratory tract infections (URI) such as the common cold [4]. In 2012, echinacea was the sixth most common non-vitamin, non-mineral supplement used by adults in the United States, used by 2.3 million adults [5]. A National Health Interview Survey found that echinacea use decreased by about one-half from 2007 to 2012 [6]. Similarly, echinacea use by children fell from the most commonly used herbal product in 2007 to the fourth most common in 2012 [5]. (See "Overview of herbal medicine and dietary supplements" and "The common cold in adults: Treatment and prevention".)
PROPOSED MECHANISMS OF ACTION — Various echinacea species including Echinacea purpurea, E. angustifolia, and E. pallida have been touted as "immune stimulants" by a number of investigators [7]. Medicinal preparations using the root and above-ground parts of echinacea species have been the subject of in vitro, animal, and human studies to evaluate their possible mechanism(s), safety, and efficacy.
Echinacea products contain a variety of bioactive ingredients including echinacosides, caffeic acids, alkylamides, polysaccharides, and glycoproteins [8]. Though several echinacea products are standardized to the amount of echinacosides, there is no general consensus on the active component(s) of echinacea responsible for its purported medicinal properties.
●In vitro activity – Echinacea causes macrophage activation and the release of tumor necrosis factor, interleukin 1, interleukin 6, and interferon [9-11]. Echinacea has been noted to have antiviral activity against influenza [12] and herpes virus [13]. Phenolic compounds present in echinacea demonstrate antioxidant activity [14]. It has also been reported to have antiinflammatory activity through inhibition of lipoxygenase and cyclooxygenase [15] and is able to stimulate the anterior pituitary-adrenal cortex.
●In vivo activity – In animal studies, echinacea affects several aspects of the immune system, in part by increasing the number of circulating white blood cells [16]. Echinacea also increases phagocytosis, promotes activity of lymphocytes, stimulates cytokine production, triggers the alternate complement pathway, and modulates apoptosis [17,18].
PROPOSED INDICATIONS AND CLINICAL TRIALS — Many clinical studies have attempted to elucidate the safety and effectiveness of echinacea. This research is challenging because there are differing opinions regarding the optimal echinacea species, plant part(s), active component(s), and dose to study. The specific echinacea products used in studies are often not standardized. However, several randomized, double-blind, placebo-controlled trials are of sufficient quality to derive useful information, particularly around the use of echinacea for upper respiratory tract infections (URI).
Upper respiratory tract infection — Echinacea is commonly used by patients for the treatment and prevention of nonspecific URI.
Treatment — In a 2014 systematic review including 15 randomized trials comparing various echinacea preparations with placebo, there was no benefit of echinacea for the treatment of viral URI [19].
Prevention — Well-designed studies of echinacea have generally not found evidence of efficacy for the prevention of community-acquired URI [4,20]. Although a 2014 systematic review found that the results of individual trials using echinacea for viral URI prophylaxis consistently demonstrated positive trends towards benefit, they did not meet statistical significance [19]. In a pooled data analysis using 9 of 10 prevention trials including 1167 patients, there was a 10 percent absolute risk reduction in URI incidence; this met criteria for statistical significance, although is of unclear clinical importance. In addition, the included studies were of low quality.
●In a randomized, controlled trial of a convenience sample (no power analysis provided) including 109 patients with more than three colds or respiratory infections in the preceding year, patients were randomly assigned to receive 4 mL fluid extract of E. purpurea or 4 mL of placebo twice daily [20]. While there were small differences favoring treatment, there were no differences between the groups in the number of infections and a nonsignificant trend toward more side effects in the active treatment group.
●In a randomized trial including 302 adults, participants received E. purpurea, E. angustifolia, or placebo for 12 weeks [4]. The time until onset of the first URI was not different among the three groups (66, 69, and 65 days, respectively).
Experimental studies have also generally not found that echinacea is effective in preventing URI after challenge with rhinovirus [4,21-23]:
●A small trial randomly assigned 48 adults to receive echinacea (2.5 mL three times daily) or placebo for seven days before and seven days after nasal inoculation with rhinovirus type 39 [23]. There was a similar rate of microbiological infection with rhinovirus in both groups (92 versus 95 percent). There was a trend toward fewer patients treated with echinacea developing clinical colds, although the results did not reach statistical significance. The small sample size, however, limits interpretation of the findings.
●A randomized trial examined the effects of three different preparations of E. angustifolia root (extracted with supercritical carbon dioxide, 60 percent ethanol, or 20 percent ethanol) and placebo in 399 volunteers who were challenged with rhinovirus [21]. Treatment was administered three times daily with a 1.5 mL tincture (containing the equivalent of 300 mg of echinacea root) or placebo for five days prior to rhinovirus challenge. Rates of infection and clinical URI were not different for either group.
SAFETY CONSIDERATIONS
Adverse effects — Although echinacea is generally well-tolerated, side effects can occasionally occur. Allergic reactions can occur in individuals sensitive to the Asteraceae/Compositae family. Patients with allergies to ragweed, chrysanthemums, marigolds, and daisies may have dermatologic reactions to echinacea [24]. One trial found that rash was also more frequent in children treated with oral echinacea compared with placebo (7.1 versus 2.7 percent) [25].
A few case reports of anaphylaxis associated with use of E. angustifolia and E. purpurea have been published [24,26].
Contraindications
Use in autoimmune disease — The immune stimulating effects of echinacea have led to concerns regarding the use of echinacea in patients with autoimmune disorders [1]. Despite these concerns, little is known regarding the exacerbation of autoimmune illnesses due to echinacea. Case reports include an exacerbation of pemphigus vulgaris, a recurrence of erythema nodosum, and a case of renal tubular acidosis due to Sjögren’s associated with echinacea use [27-29]. By contrast, a pilot study in patients with low-grade autoimmune idiopathic uveitis found that treatment with E. purpurea extract was associated with shorter duration of steroid treatment required to induce remission [30].
Use in pregnancy — A cohort study followed pregnant individuals who contacted the Toronto Motherisk Program about gestational use of echinacea [31]. There were 206 people who used echinacea products in pregnancy (112 during the first trimester). No increased risk for still births, spontaneous abortions, and major fetal malformations occurred in those who used echinacea compared with 206 controls matched for age, alcohol use, and cigarette smoking. Similarly, the Norwegian Mother and Child Cohort Study identified 363 pregnant individuals reporting echinacea use with no associated increased risk of congenital fetal anomalies or poor pregnancy outcomes [32]. A systematic review also did not find evidence suggesting that echinacea is teratogenic [33]. Nonetheless, it is prudent to avoid echinacea during pregnancy and lactation.
HERB-DRUG INTERACTIONS
●Because of its immunostimulating activity, echinacea may interfere with immunosuppressant therapy [1] and should be avoided in patients taking immunosuppressants.
●There is in vivo evidence that echinacea may effect CYP3A and CYP1A2 activities [34], although there are no reports of clinically significant adverse interactions in patients taking drugs metabolized by these enzymes. Nonetheless, caution should be advised in those taking such medications.
●In one in vitro study, echinacea extracts stimulated the proliferation of cervical and breast cancer cells despite exposure to doxorubicin [35]. The clinical relevance of this potentially harmful interaction between echinacea and doxorubicin is not clear and requires further study.
ADMINISTRATION
Dose — There is substantial product variation in species of echinacea, part of plant used, formulation, and extraction method, and thus dosages are not standardized. Typical dosages recommended by manufacturers and herbal experts and used in studies are 300 to 400 mg of dried extract taken orally three times daily, one cup of tea (1 gram root in 150 mL boiling water for 5 to 10 minutes) three times daily, and 0.25 to 1 mL of liquid alcohol extract three times daily [1].
Standardization — Many different preparations of echinacea are available. Despite attempts by the US Food and Drug Administration (FDA) to improve regulation of quality and safety standards for dietary supplements [36], experts have criticized these standards as insufficient and enforcement activities as inadequate [37,38]. Until the effectiveness of these regulations has been confirmed, patients who choose to use echinacea can use products that have passed specified quality criteria by independent commercial laboratories. (See "Overview of herbal medicine and dietary supplements", section on 'Quality and efficacy'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: The common cold in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Not effective for the treatment of viral upper respiratory infections – Although echinacea may have some immune stimulating effects, the evidence does not support its efficacy in treating the common cold and we recommend not using it for this purpose (Grade 1B). (See 'Treatment' above.)
●Likely ineffective in preventing viral upper respiratory infections – Echinacea may have a weak effect on the prevention of colds, but the questionable benefit may not warrant possible mild adverse events. Pending more compelling evidence of benefit, we suggest not using echinacea for prevention of upper respiratory tract infection (URI) (Grade 2C). (See 'Prevention' above.)
●Safety – Echinacea appears to be relatively safe, although allergic reactions have been reported. (See 'Safety considerations' above.)
●Lack of standardization – As with other herbal preparations, variability of echinacea preparations is an obstacle to its potential use by patients and prescription by clinicians. (See 'Standardization' above and "Overview of herbal medicine and dietary supplements".)
