Clinical use of echinacea

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 archeologic 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 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 approximately 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 anti-inflammatory 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 and studies have been small and of variable quality. Further, the specific echinacea products used in studies are often not standardized. However, meta-analysis of the available randomized, double-blind, placebo-controlled trials may be informative, 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 — Although echinacea may have a role in preventing community-acquired URIs, the certainty of evidence regarding its benefit is low, and the likely magnitude of reduction in cold incidence is small and offset by side effects. Well-designed, randomized trials have generally not shown statistically significant differences between echinacea preparations and placebo, but their small size limited precision [4,20]. In an exploratory meta-analysis of nine mostly low-quality trials, prophylactic echinacea reduced the number of participants with at least one cold episode (relative risk 0.83; 95% CI 0.75-0.92; I² = 0 percent; number needed to treat = 10) [19,21]. It is not clear if this difference is clinically meaningful to patients or if the quality of evidence is sufficient to support its use for this purpose. Moreover, adverse events occurred more frequently in those randomized to echinacea and most commonly included headache, nausea, and a bad taste.

A subsequent trial that randomized 201 asymptomatic children to Echinaforce (400 mg freshly harvested E. purpurea alcoholic extract) versus vitamin C (50 mg) found fewer URI episodes at four month follow-up in children randomized to echinacea (odds ratio 0.52; 95% CI 0.30-0.91) [22]. Children randomized to echinacea were also less likely to have any cold episodes (39 versus 55 percent), receive antibiotics (5.8 versus 13.5 percent), have URI-related complications (eg, pneumonia, otitis media, sinusitis), or have influenza detected (3 versus 20 detections, p = 0.012), compared with those assigned to vitamin C. Adverse events occurred slightly more frequently in those randomized to vitamin C. These findings await replication in larger clinical trials.

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 [23]. One trial found that rash was also more frequent in children treated with oral echinacea compared with placebo (7.1 versus 2.7 percent) [24].

A few case reports of anaphylaxis associated with use of E. angustifolia and E. purpurea have been published [23,25].

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 [26-28]. 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 [29].

Use in pregnancy — A cohort study followed pregnant individuals who contacted the Toronto Motherisk Program about gestational use of echinacea [30]. 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 [31]. A systematic review also did not find evidence suggesting that echinacea is teratogenic [32]. 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 [33], 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 [34]. 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 doses are not standardized. Typical doses 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 [35], experts have criticized these standards as insufficient and enforcement activities as inadequate [36,37]. 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 5^th to 6^th 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 10^th to 12^th 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.)

●Uncertain efficacy in preventing viral upper respiratory infections – We do not recommend for or against echinacea for prevention of upper respiratory tract infections. Although echinacea may have a weak effect on the prevention of colds and some of their complications, it requires taking a daily pill that can have side effects. (See 'Prevention' above.)

●Safety – Echinacea appears to be relatively safe; although, allergic reactions and side effects of headache, nausea, and bad taste 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".)