Introduction     ▲

Compared with other medicinal herbs, history of usage for healing of echinacea is recent[1].

The plant is native to North America and was used for medicinal purposes by the original inhabitants of the continent before the Discovery. There are documents about this usage dating from the eighteenth century. Echinacea has been used for external application in the healing of wounds, burns and insect bites. The root was used chewed as a remedy for toothache and throat infections. It was also used for coughs, pains, snake bites and epigastric pain 2].

Biology     ▲

Echinacea angustifolia is a herbaceous plant of the family Asteraceae, native to North America that has similar characteristics as the purple and pale varieties, of which slightly differs its morphology. The description of properties and studies listed below specifically deal with Echinacea angustifolia, although in many cases the data are shared with the other varieties, as the authors of the original papers make no distinction between them.

Echinacea angustifolia is, as stated, a herbaceous plant reaching up to a meter high. The flowers have floral rays, narrow, hence the name angustifolia and are pinkish. The disk flowers are tubular and pale yellow. Floral disk is spiny, like fruit.

Composition     ▲

Echinacea contains an essential oil, which represents 1.5% of the weight of the plant, mainly composed of humulene. Also contains echinacoside and various high-molecular weight polysaccharides composed mainly of rhamnose, arabinose, xylose and galactose.

In the composition of Echinacea angustifolia are various organic acids (cichoric, chlorogenic acid, isochlorogenic, caffeic, cafeoilethylic, verbascosideo, etc) and a composite resin containing fatty acids (oleic, linoleic, palmitic and cerotinic).

Other components were identified as isobutylamide, polyacetylene, 8-pentadecene-2-one, 1,8 pentadecadiene, echinolone, cynarin, inulin, and pentosan. Cichoric acid and verbascoside predominated in extracts of E. purpurea root whereas cynarine and dodeca-2E,4E,8Z,10Z/E-tetraenoic acid isobutylamide were the major chemicals characteristic of E. angustifolia root extracts[3].

The total phenolic content in E.Angustifolia is 10.49 mg/g while in the variety Purpurea is 23.23 mg/g[4].

All plant tissues contain acetaldehyde, dimethyl sulfide, camphene, hexanal, beta-pinene, and limonene[5]. Aerial parts of the plant contain beta-myrcene, alpha-pinene, limonene, camphene, beta-pinene, trans-ocimene, 3-hexen-1-ol, and 2-methyl-4-pentenal. Root tissues varieties contain alpha-phellandrene (present only in the roots of E. purpurea and E.angustifolia), dimethyl sulfide, 2-methylbutanal, 3-methylbutanal, 2-methylpropanal, acetaldehyde, camphene, 2-propanal, and limonene[5].

Traditional applications     ▲

It is primarily used the root. More rarely used the whole plant. It is considered that the fresh root is more potent than dry.

Popularly is admitted that it is an organic stimulant of defenses, therefore used for the treatment and prevention of viral respiratory diseases such as colds and flu. Before the antibiotic era, during the second half of the nineteenth century and the first thirty years of the twentieth century, Echinacea was the treatment of choice for infectious processes [6]. Probably for this reason, echinacea has been improperly called "antibiotic plant".

The external application is considered useful for the treatment of ulcers and wounds.

Despite its relatively recent use as a medicinal plant, its use has spread worldwide. For example, in a rural community in New South Wales, 62.7% of respondents to a questionnaire reported using one or more alternative therapeutic resources, including medicinal plants as echinacea and garlic. These people got the information for use primarily in his circle of friends [7].

A lower figure, although significant, show some gated communities, like the Amish. Among these, 36% of 66 women interviewed said to use at least one resource from complementary medicine and/or alternative. Ten of these women, who were pregnant when they carried out the study, reported to use medicinal herbs during pregnancy, including echinacea[8].

In agreement with these findings, a study in Vancouver showed similar figures. Among 575 patients who were administered a questionnaire (84% response), showed that 34% reported consuming medicinal plants. Of these, 39% reported daily use these plants and echinacea was the agent most consumed. Less than half of these patients referred to their GP this consumption[9].In another study, also in Canada, one-third of the patients admitted to a hospital for surgery reported having consulted a naturopath, while the percentage of patients who had taken prior to any intervention alternative medicine product was 17%[10].

Globally it is estimated that 3 in 10 patients used herbal remedies each year [11].

Among the peri-and postmenopausal women, 36.5% used daily alternative medicine remedies. About half of these patients (48.4%) used three or more botanical dietary supplements [12]. Echinacea is Among the most used (15.44%). The 70% of respondents had not reported to their doctor the use of these alternative resources.

In children with attention deficit-hyperactivity disorder, the prevalence of use of herbal therapy was 20%. 15% of patients had received these remedies over the last year. More medicinal plants used were ginkgo biloba, echinacea and St. John's wort, usually administered to treat behavioral disorders.

Not always what the consumer is buying is equal to what the label says.A study published in 2003 in Archives of Internal Medicine evaluated by thin layer chromatography different content from commercial preparations of echinacea. Six of 59 samples did not contain a detectable amount of the plant. Only 52% of those (n = 31) contained what is stated on the package, while nine of the 21 samples prepared nonstandard met the quality requirements [13].

In 2001, Lanski et al[14] reported the use of medicinal plants in children according to data obtained in the emergency department of a hospital. 45% of caregivers of children, whose average age was 5.3 years, recognized administer medicinal plants to their children. At least one third of the cases involved echinacea. Over three-quarters of the caregivers did not believe this had any adverse effect on small patients.

The 57% of patients undergoing elective surgery who responded to a survey claimed to have used medicinal plants at some point in their lives. Echinacea was consumed by 48% of responders. Those patients with self-perception of being in good health and women undergoing gynecological surgical procedures were the biggest users of medicinal plants [15].

A survey conducted in 2002 on children showed that 21% of parents and 4% of patients from a pediatric surgery service were consumers of medicinal plants, mainly echinacea. Almost half of these consumers did it simultaneously with prescription drugs[16].

A study by interviewing 400 Norwegian women who had recently given birth, reveals that 36% had used herbs during pregnancy, at an average amount of 1.7 plants per woman and increasing ratably over the period of gestation . Among the plants, echinacea was the most consumed [17], which in turn was also the best known[18].

Among the older population, the use of medicinal plants has been increasing over the past five years. According to published data, 12.9% of the U.S. elderly population had used a botanical supplement during the previous twelve months. This consumption was higher among persons 65-69 years old, women, ethnic minorities, greater socioeconomic and cultural status or higher self-perception of being in good health. As in other studies, echinacea appeared in prominent places in terms of consumption [19]. For most respondents, the main reason of its use resided in higher profits with the combined use of conventional therapy and medicinal plants.

Echinacea is not only consumed in America. A study of Turkish students in 2004 reported an overall prevalence of botanical supplements consumption of 16.5%. The reasons given for this were generally increased energy and vitality, lose weight and get improved athletic performance. In 26 of the 308 consumers of these remedies adverse reaction occurred. The most frequently used plant was echinacea (38.6%) [20].

Among Italian women treated as outpatients at a university hospital, a study published in 2006 on a random sample of 1044 women, reflects a prevalence of consumption of 47% over the previous year [21]. Often (35.2%), these remedies are administered to children or take them also during pregnancy. Echinacea was included among the remedies more consumed.

A study conducted in 2002 in a hospital in Melbourne [22] by performing a pre-admission questionnaire prior to surgical procedures, consumption of medicinal plants showed a prevalence of 14.3%. 61.4% of patients who consumed were women. Among the products most used was echinacea.

The alternative supplement use was higher among Hispanic children(33%) than among Caucasians(9%). Among the most used substances were herbal teas(56%) and echinacea 14%)[23].

Among plastic surgery patients, echinacea was the third resource used(14%)[24]. Among patients with cardiovascular disease, echinacea was also one of the plants or alternative remedies most used[25].

According to data from the Canadian National Population Health Survey (NPHS) 2000-2001, the three most used alternative resources included echinacea, garlic and glucosamine [26].

In Ireland, a survey revealed that 57% of parents report use alternative resources for their children. In addition of vitamins and fish oil, the most widely used resource was echinacea (26%)[27].

According to data from a survey on elite athletes, 31% reported using echinacea, along with protein, caffeine, various vitamins, iron and creatine [28].

Between pre-and postmenopausal women, 64% reported using alternative resources always, while 34% said they were frequent user of these, being echinacea the most used product [29].

Among adults who use medicinal plants, 41% reported using echinacea. Next in frequency of consumption are ginseng (25%), ginkgo (22%) and garlic (20%) [30].

Experimental studies     ▲

Notice to reader

The findings of the various experimental studies are not directly applicable to humans and should not provide a basis for arguing for its application to people. By contrast, neither animal physiology nor the conditions of each experiment and the doses applied, which are often unacceptable in man, allow conclusions for its direct application.

Antiinflammatory activity

Several studies seem to have established the anti-inflammatory activity of Echinacea angustifolia. Thus, the aqueous extract of the root of the plant has shown anti-inflammatory effect locally in an experimental animal model [31]. According to survey data, this activity could reside in the high molecular weight polysaccharides. Previously, it had formulated the thesis that the polysaccharide fraction would have anti-inflammatory properties[32], as evidenced in the croton oil test and carrageenan-induced edema, which would be slightly lower in potency to indomethacin.

Alkylamides contained in echinacea have ability to inhibit cyclooxygenase A in vitro [33] [34]. These substances have an activating effect on macrophages [35], possibly increasing arginase activity [36]. According to some studies in vitro, Echinacea extract significantly reduces the presence of mediators of inflammation [37] [38]. Alkylamides inhibit lipopolysaccharide-induced inflammation in the blood and appear to exert a modulatory effect on the expression of cytokines [39].

Some studies seem to indicate that Echinacea extract could inhibit the release of cytokines and thereby reduce the inflammatory [40] [41], specifically IL-6 and IL-8 induced by rhinovirus.

Immunomodulatory effect

Several observations identify an immunostimulatory effect overall of the extract of Echinacea[42], in particular on the activities as phagocytosis, bactericidal power and metabolism of peritoneal macrophages [43] [44], as well as those of the lung and spleen in normal rats [45] . This extract would increase the total weight of the spleen compared to controls [43].

The group of patients treated with echinacea showed a significant increase in primary and secondary response to antigen IgG, suggesting stimulation of immune function by increasing production of specific IgG [45].

A double-blind placebo controlled on Sprague-Dawley male rats produced a significant increase in mononuclear cells[46]. According to the study data, the aerial parts of Echinacea would affect the level of circulating mononuclear cells and IL-2.

One study seems to show the influence of alkylamides on gene expression of tumor necrosis factor and its influence as immunomodulator [47]. Such alkylamides modulate the immune response in macrophages, although chicoric acid would also play a secondary role in this effect. [48]

Polinácea, an echinacea root extract containing echinacoside, the polysaccharide IDN 5405 and isobutyl amide fraction, appears to stimulate immune function, which would be revealed by the rate of production of gamma interferon in cell cultures of T lymphocytes. As can be seen in the study, Polinácea show a stimulating action in vivo reducing the mortality induced by Candida in pretreated mice both normal as treated with cyclosporine [49].

Immunostimulatory activity would reside more in the main water-soluble substances than in the lipophilic, especially polysaccharides linked[50].

Effect on tumor

Echinacea would modulate apoptosis of spleen lymphocytes in mice [51].

Echinacea would have proliferative effect on cells pretreated with doxorubicin [52], which could have an opposite effect of the antitumor substance. These results require further validation.

Applied in vitro on some tumor cell lines, such as those from cell cultures of colon or pancreas cancer, echinacea and other plants seem to reduce the viability of these cells a dose dependent manner [53].

Teratogenic effects

Compared with levamisole, echinacea would have a prophylactic effect against velopalatal fissure caused by phenytoin in mouse fetuses [54], although the data are not statistically significant.

Photoprotective effects

A study evaluating the free radical degradation of collagen showed a protective effect against this degradation by this order of potency: echinacoside -> chicory acid -> cynarine -> caffeic acid -> chlorogenic acid, suggesting the possible use of Echinacea extract for topical prevention and treatment of photodamaged skin produced by UVA / UVB, in which oxidative stress plays an important role [55].

Pharmacological data     ▲

Echinacea based preparations have a weak potential to interact with the CYP450 isoenzymes, including CYP1A2 and CYP3A4, there being no communication about clinical influence of such interactions [56] [57].

Experimental data show a slight influence on the different isozymes, strong on the CYP3A4 and weak on CYP2D6 [58] [59], although the inhibitory potency is extremely variable depending on the substrate being considered. Apparently the alkylamides are partly responsible for this interaction. Recent research indicates that prolonged use of echinacea has minimal risk for the user of drugs metabolised by P450 [60]. Care must be taken, however with the potential increase in risk in patients receiving paracetamol, since can increase risk of hepatotoxicity [61].

There are reasons to discourage long-term use of echinacea preparations with anticancer drugs, although possible interactions between echinacea and these substances, mediated by nuclear receptors, are not yet well established [62]. There is also sufficient evidence of potential interactions with antiretroviral drugs [63], so that their combined use should be avoided.

Interactions with substrates of P-glycoprotein does not appear to be relevant. Thus, a study of the possible interaction with digoxin, P-glycoprotein substrate, showed no significant influence on the pharmacokinetics of this drug[64].

Caffeic acid is not detectable after ingestion of the preparation, probably because it does not cross the intestinal barrier [65]. By contrast, alkylamide is rapidly absorbed, being detected after 20-30 minutes [66], being identifiable in the plasma of healthy volunteers for 12 hours, reaching peak concentration at 2.3 hours of ingestion[67].

Clinical studies     ▲

Clinical trials:

Echinacea is one of the medicinal plants most and best studied in the scientific literature. It has a good amount of trials with a variable methodological quality, from acceptable to excellent, although results are controversial.

Most of the studies deal with the prevention or treatment with this plant of upper respiratory infections, but also for other clinical applications. So, in this regard, a clinical trial in 30 women with idiopathic megacystis using a commercial preparation containing echinacea and sabal serrulata seemed to improve some parameters of the functionalism of the bladder and detrusor tone [68]. <

Regarding the preventive aspects, a controlled clinical trial with good methodological quality during twelve-month, found no significant difference in prevention versus placebo of both extracts, echinacea angustifolia and echinacea purpurea [69]. Also, another controlled clinical trial versus placebo, published in NEJM on a sample of 437 volunteers showed no significant differences on the prevention or treatment of experimental rhinovirus infection in patients treated with echinacea[70]. However, Cohen et al found a preventive effect on upper respiratory infections from a preparation containing echinacea, propolis, and vitamin C, that, regardless of the objections about the quality of the study, cannot reach interpretable conclusions[71].

As for treatment of the common cold, a combination of plant roots (Echinaceae, Baptisiae and Thujae) appeared be effective and safe in the treatment of common cold, with rapid improvement of symptoms, higher than the control group in a controlled clinical trial versus placebo[72 ]. In contrast, the work of Turner et al concluded, in a study published in 2000, that the plant does not have a significant effect on the severity or course of experimental rhinovirus infection[73].

Another controlled clinical trial versus placebo evaluating early intervention on the common cold by treatment with a standard prepared echinacea reduced the severity of symptoms in patients treated with the preparation, although the authors recommend conducting more studies [74]. A study of only 95 patients, treated early with a commercial preparation of echinacea or placebo appeared to be effective for the symptomatic relief of patients [75], although the small number of patients is a serious objection to obtaining valid conclusions. By contrast, another trial, this time made ??with dried and encapsulated echinacea showed no significant differences versus placebo in the treatment of the common cold [76].

A clinical trial conducted in 24 healthy volunteers showed a significant increase in erythropoietin in subjects treated with 8000 mg of echinacea compared with placebo treatment (p <0.001). Also significantly elevated interleukin 3 compared to controls (p <0.011) [77]. It is unknown whether these effects have any clinical significance.

A prospective study, which analyzed the potential risks of fetal malformation attributable to taking echinacea during pregnancy, showed no significant difference compared to controls [78]. However, the low statistical power of the study does not allow extrapolate the findings of the authors to the general population.

Systematic reviews:

In a review were evaluated five clinical trials on the immunomodulatory activity of preparations of Echinacea on 134 healthy volunteers. The primary endpoint was the relative phagocytic activity of neutrophils, while the secondary was the number of leukocytes in peripheral blood[79].

In two of the five studies significant differences were found with respect to the primary variable. The secondary endpoint did not change in any of the studies. This disparity of results provides elements for the implementation of new and more extensive studies, both in volunteers and in patients with different conditions.

Another review of published trials on efficacy and safety of echinacea concludes that plant derivatives may be beneficial in the early stages of treatment of acute upper respiratory processes, however, there is little scientific support for its prolonged application on prevention of infection of respiratory tract [80].

A Cochrane Collaboration review notes that most of the available studies show positive results regarding the prevention and treatment of common cold with echinacea. But for the authors of the work, there is not enough scientific evidence to recommend a specific preparation of echinacea or a product for the treatment or prevention of the common cold [81].

A systematic review of the scientific literature spanning from 1961-1999 collects twelve trials on the application of Echinacea in upper respiratory infections. From the five published since 1997, two showed no efficacy for the treatment or prevention of upper respiratory infection, while the remaining three ends that Echinacea was effective in reducing the frequency, duration and severity of common cold [82 ].

A systematic review published in 2006 in the Canadian Journal of Clinical Pharmacology, indicates that there is good scientific evidence based in a prospective observational study about oral consumption of echinacea during the first trimester of pregnancy and not increases the risk of major malformations. It also indicates that, in the opinion of experts, oral consumption of echinacea at recommended doses is safe during pregnancy and lactation [83]. The same work concludes that echinacea should be used with caution during breastfeeding.

A meta-analysis of data from three studies (out of a total of 234 preselected works) dealing on experimental rhinovirus infection, highlights a likelihood of symptomatic rhinovirus infection 55% higher in patients who received placebo versus those treated with echinacea although the score of the intensity of symptoms showed no significant differences between placebo and patients receiving echinacea [84].

A meta-analysis published in 2007 in the prestigious journal The Lancet , which assesses the effect of echinacea on the incidence and duration of the common cold and including fourteen items, suggests that echinacea decreases by 58% the likelihood of developing cold symptoms (OR 0.42, 95% CI 0.25 to 0.71, P <0.001). Catarrhal episodes lasted an average of 1.4 days less (95% CI -2.24 to -0.64, p = 0.01)[85].

A systematic review of the Cochrane Database published in 2006 [86] recorded no preventive differences in favor of echinacea for upper respiratory infections. However, in nine studies found significant effects in the symptomatic treatment of these conditions with echinacea, although in six others there were not differences with respect to placebo. The authors conclude that some of the preparations based on Echinacea purpurea might be effectives in the early treatment of upper tract infections, being to demonstrate the beneficial effect of other preparations of echinacea or preventive treatment of upper tract infections based in this plant family.

A review of Carr and Nahata, based on six clinical trials published up to June 2005 concluded that echinacea did not reduce the duration or extent of upper respiratory infections, although it decreases nasal secretions (p <0.01), noting that this plant was associated with a higher frequency of skin rash compared with placebo (p = 0.008)[87].

A systematic review including 322 studies indicated that, of the nine studies initially selected, only two met the quality requirements of the established protocol for review. In the opinion of the authors, both studies provided negative data, and concluded that the results suggested that the potential effectiveness of echinacea in treating the common cold had not been established[88].

Adverse reactions     ▲

According to available data, the risk of adverse reactions with echinacea is 1 in 100,000, which makes this plant considered as relatively risk-free[56].

Before and after surgery, a significant number of patients are turning to alternative medicine[93]. These patients seem to use these resources more frequently than the general population. For example, Tsen et al report that 22% of patients undergoing preoperative examination take herbs[94]. Also, Kaye et al report that 32% of patients seen in an outpatient surgery admit using these alternative resources[95]. Given the possible adverse effect on the course of the intervention of the administration of medicinal plants, it is necessary that the doctor specifically inquire about the use of such plants.

Patients requiring immunosuppression as well as waiting for a transplant should avoid continue consuming echinacea. In contrast to the immunostimulatory effect in the short-term use, continued use of the plant, especially the use of longer than eight weeks may involve the risk of promoting immunosuppression, with certain theoretical risk of postoperative complications, such as poor wound healing and increased susceptibility to opportunistic infections.

Different authors recommend patients to suspend all dietary supplements at least one week before undergoing any surgery of any importance or diagnostic procedures[96].

Echinacea has been associated with allergic reactions, including one case report of anaphylaxis[97], so it should be used with caution in patients with asthma, atopy or allergic rhinitis. Echinacea has a potential risk of liver toxicity, although there is no detailed documentation of cases[98]. In the absence of sufficient information on hepatotoxicity, it is prudent to act with extreme caution in patients with impaired liver function known, so treatment should be discontinued when echinacea provides a possible liver or circulatory compromise, as often happens in the surgical manipulation or general anesthesia[93].

Data from published studies and established pharmacovigilance programs suggest that adverse reactions caused by echinacea are referenced unfrequently. However, digestive discomfort and rashes are the most common side effects[2]. In rare cases, echinacea is associated with potentially severe allergic reactions.

Despite the large number of trials evaluating the efficacy, rarely has been considered the safe use of the derivatives of this plant. Probably the short-term use is relatively safe, with a slight increase in adverse effects temporary and reversible. The association of Echinacea with allergic reactions are probably rare, however, patients with a history of asthma or other allergic diseases should consider this risk before taking any preparation of this plant. Similarly, the absence of sufficient information on the use of echinacea during pregnancy or lactation should be taken into account.

Echinacea is the second supplement related to adverse reactions recorded in the database of the California Poison Control System, representing more than 7% of cases, being the first plant in importance of the database[99].

Adverse effects attributable to Echinacea are rare and consist primarily of adverse reactions, which in some cases can be severe. The Adverse Drug Reactions Advisory Committee (ADRAC) of Australia received eleven communications of adverse reactions attributable to echinacea from July 1996 to September 1997, including cases of hepatitis, asthma, generalized rash, with or without symptoms of myalgia and nausea, episodes of vertigo with simultaneous swelling of the tongue and anaphylaxis [100], No systematic study has reported adverse effects with this popular plant. An underpowered study did not find evidence of adverse pregnancy after consumption of this plant.

A recent revision of the ADRAC database rises to 51 cases reported to the agency, of which 26 are probably mediated by IgE (4 anaphylaxis, 12 cases of acute asthma, 10 cases of urticaria or angioedema) [101]. Some atopic patients have hypersensitivity to this plant in the absence of prior contact, which suggests to some authors that there is a kind of cross-reactivity with some other environmental agent. By contrast, the three varieties of Echinacea are one of the resources more used in alternative medicine for the treatment of allergic diseases, especially respiratory[102].

Echinacea consumption has been associated with numbness of the tongue[103]. Patients suffering lymphoma should be warned of the risks of using echinacea[104]. Patients with diseases in which the immunity plays a major role can be seen worsen its course when receiving echinacea. For example, there have been two cases of exacerbation of pemphigus vulgaris after taking echinacea supplements[105].

In 2001, Soon describe a case of recurrent erythema nodosum associated with echinacea consumption, perhaps related to the immunostimulatory effect of the plant[106].

One patient with a prior history of atopy presented a severe anaphylactic crisis after ingesting a commercial preparation of echinacea extract. Skin tests and RAST showed hypersensitivity to the plant [97]. Patients with previous allergic manifestations has a high risk of severe reactions to complementary medicines, including this plant.

Echinacea may cause hepatotoxicity and should not be used in conjunction with other potentially hepatotoxic substances such as anabolic steroids, amiodarone, methotrexate, or ketoconazole[107].

Conclusions     ▲

There are insufficient data to formally establish the efficacy of echinacea definitively [89] [90]. Were identified numerous components of the plant, although the mechanism of action is today unknown. It is not know basic pharmacological data as bioavailability, relative potency or the synergistic effects of the different components.

An overall assessment of the available documentation does not exclude that echinacea is effective in the treatment of common cold, although this may not be applicable to all preparations of the plant. The differences between the various preparations makes it even more difficult to assess and compare them, since there is no known active ingredient as a reference [91].

It would be necessary to conduct prospective studies of sufficient power and appropriate methodology that could confirm the benefits of echinacea[92].

References     ▲

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Date page update: February 6, 2009.