Echinacea is native to the United States and a small region of southern Canada. There are nine species of Echinacea: E. angustifolia, E. dicksoni, E. dubia, E. gloruisa, E. pallida, E. paradoxa, E. purpurea, E. simulate, E. angustifoliae; however, only three of the species are normally harvested for medicinal purposes: E. angustifolia, E. pallida, and E. purpurea. Originally, Echinacea was used in North America by Native Americans for therapeutic uses such as blood purification, snake bites, infections, and malignancy. In the late 1800’s a Nebraska physician, HCF Meyer, learned of its being used by Native Americans and proposed its uses to a pharmaceutical manufacturer, Lloyd Brothers of Cincinnati. The physician expounded on the uses of Echinacea proposing that it could be used for rheumatism, streptococcal erysipelas, stomach upset, migraines, pain, sores, wounds, eczema, sore eyes, snake bites, gangrene, typhoid, diphtheria, rabies, hemorrhoids, dizziness, herbal poisoning, tumors, syphilis, malaria, and bee stings. At this point it began to be marketed as an anti-infective (Cupp, 2000; Blumenthal et al., 2000; Rotblatt and Ziment, 2002).
Today, Echinacea is mostly used as an immune modulator to aide the body in fighting or preventing infections, such as the common cold, flu, and chronic infections such as respiratory and lower urinary tract infections. In addition, there have been a few studies that support its use for chronic candidiasis. The active components of Echinacea are phenolic compounds, terpenoid compounds, nitrogenous compounds, such as alkylamides and alkaloids, and carbohydrates, such as polysaccharides. Polysaccharide components have been proven to activate macrophages (stimulation of phagocytosis), increase leukocyte mobility, and increase cellular respiration that may lead to the attack of tumor cells (increased tumor necrosis factor) and microorganisms (Cupp, 2000; Blumenthal et al., 2000; Rotblatt and Ziment, 2002).
Echinacea seems to be a good example of an herb that proves there is no such thing as a generic herbal medicine. The quality of Echinacea in studies has definitely had some influence on the confounding results of studies. As there are a number of pharmacologically important compounds in Echinacea, researchers should be careful to characterize the nature of their preparation. Likewise, consumers and health care professionals should be aware of the potential of buying poor quality product.
The Common Cold and Flu
In a recent randomized, double-blind, placebo-controlled study on the efficacy of a standardized preparation of Echinacea purpurea (100 mg freeze-dried pressed juice from the aerial portion of the plant 3 times daily) on the severity and duration of the common cold. Of the 180 patients that were enrolled and given the active or placebo treatment, no statistical differences were found between groups in the total symptom scores, or mean individual scores, nor was there a difference noted in the times to resolution of symptoms (Yale and Liu, 2004).
In another recent randomized, double-blind, placebo-controlled study Echinacea was again studied to elucidate it effects on the common cold. The authors theorized that much of the inconclusive nature of the studies to date were due to the utilization of poorly standardized products that were devoid of active components. Therefore, they used a preparation that was standardized to alkamides (0.25 mg/ml), cichoric acid (2.5 mg/ml) and polysaccharides (25 mg/ml) (Echinilin, Natural Factors Nutritional Products, Inc.). The 282 healthy subjects were given either echinacea or placebo to take at the onset of the first symptom related to a cold, consuming 10 doses on day one, and 4 doses on the subsequent seven days. The total daily symptom scores were 23.1% lower in the Echinacea group than in the placebo, and the response rate was greater in this group throughout the study (Goel et al., 2004).
A randomized, double-blind placebo-controlled community-based trial was conducted to determine the efficacy of dried, encapsulated, whole plant Echinacea as early treatment for the common cold. The study concluded that compared with placebo, unrefined Echinacea provided no detectable benefit or harm for those who had the common cold. The study was designed with a power of 80% requiring 150 participants. The study enrolled 148 participants (Barrett et al., 2002).
In another randomized double-blind placebo-controlled study, researchers determined the efficacy of an Echinacea compound herbal tea preparation given at early onset of cold or flu symptoms. The study concluded that treatment with the Echinacea herbal tea was effective for relieving symptoms in a shorter period of time that a placebo. The placebo used was a different herbal tea marketed to promote healthy digestion and that should not have improved or worsened the common cold or flu symptoms (Lindenmuth and Lindenmuth, 2000).
Researchers of an another randomized placebo-controlled double-blind study wanted to determine the effect of fluid extract (Madaus AG, 4 mL twice daily for 8 weeks) of E. purpurea on the incidence and severity of colds and respiratory infections. The study concluded that treatment with fluid extract of E. purpurea did not significantly decrease the incidence, duration or severity of colds and respiratory infections compared to placebo when tested in 109 participants (Grimm and Muller, 1999).
Four types of Echinacea preparations were studied in 246 people who easily caught colds. The treatment groups were given: a) an E. purpurea crude extract consisting of 5% root and 95% above ground parts (Echinaforce®, 6.78 mg/tablet, two tablets, three times daily); b) the same extract at a higher dosage (48.27 mg/tablet, two tablets, three times daily); a unspecified crude extract of the root (E.purpurea, 29.60 mg/tablet, two tablets, three times daily); and d) placebo. The participants were instructed to start taking their medication as soon as they felt a cold coming on until it was finished (not to exceed 7 days). The placebo and treatment d) produced similar results; whereas, the a) and b) treatments produced an improvement of cold symptoms by 62.7% and 64%. The physicians found Echinacea preparations to be 70% effective, while the patients judged them to be 80% effective. The authors concluded that Echinacea was an effective and low-risk alternative for treating the symptoms of the common cold (Brinkeborn et al., 1999).
The expressed juice of the aerial parts of Echinacea purpurea (Echinagard®) was studied in a placebo-controlled study of 120 patients who presented with the first signs of the common cold. There was a highly significant decrease in the median time required before the patients improved in the treatment group vs. placebo (zero vs. five days); in those patients determined to have developed “real colds”, the difference between the treatment and placebo groups was 4 days vs. 8 days, respectively (Hoheisel et al., 1997).
An herbal formulation containing Echinacea purpurea root extract (25 mL), vitamin C (100 mg), fennel seed extract (10.3 mg), eucalyptus leaf extract (12.3 mg), and rosemary leaf extract (20.1 mg) was studied in 32 patients against the common cold. The other herbs in the formulation were added to provide expectorant and antiseptic properties. The groups were given 4 tablets of either placebo or the herbal formulation for 44 days, and evaluated based on the amount of discharge of the thin nasal mucus they produced and the number of tissues they used. The results of the groups were significantly different: the placebo group used a mean number of 1,168 tissues and recovered in 4.37±1.57 days, and the treatment group used 882 tissues and recovered in 3.37±1.25 days (Scaglione and Lund, 1995).
The expressed juice of Echinacea purpurea (Echinacin® 4 mL, twice daily for 8 weeks) vs. placebo was studied in 108 patients who had frequent cold infections. The patients who received the Echinacea treatment took a longer period of time until contracting the cold: 40 days for the treatment group vs. 25 days for the placebo. Also, 35.2% of the patients who received the treatment remained without infections vs. 25.9% of those who received placebo. The placebo group contracted infections that were more severe, and they also showed evidence of a weakened immune system (Schöneberger, 1992).
General Immune Function
A systematic review of the trials in which Echinacea was used as an immunomodulator (26 total) concluded Echinacea to be an effective immunomodulator. However, the authors also noted that the studies were not high quality, and they recommended more well designed clinical trials to better ascertain the doses for specific conditions and preparations (Melchart et al., 1994).
A study of the immunological changes produced by an extract of E. purpurea in 12 men found a 120% increased rate of granulocytic phagocytosis. This was compared against a placebo group which only showed a 30% increase over the same period of time. After cessation of treatment, phagocytosis decreased to normal levels in 3 days. No changes were found in the immunoglobulin and leukocyte levels, or the erythrocyte sedimentation rate (Jurcic et al., 1989).
Exercise-induced immunosuppression was studied in 42 male tri-athletes. Three groups comprising E. purpurea extract, magnesium supplement, and placebo treatments were formed and followed as the athletes underwent regular competitive sprint training. The magnesium and placebo treated groups gave similar results, but the Echinacea group exhibited significantly enhanced exercise-induced decrease in levels of soluble IL-2 receptor (sIL-2R), significantly greater exercise-induced levels of urine IL-6, and significantly greater exercise-induced increases in cortisol concentrations. It was noted that the most common reported cytokine responses to strenuous exercise are increased in the release of IL-6 and sIL-2R and IL-6 in the acute phase response to injury or infection. The absence of a significant decrease of NK cells in the Echinacea groups suggested a counter-effect of cortisol on these cells (Berg et al., 1998)
Safety / Dosage
Since there are many types of Echinacea preparations available, and several immunologically-active compounds in Echinacea, dosage recommendations are varying. In the United States, commercial extracts are typically standardized to the echinacosides and 4-sesquiterpene esters; however, it has been suggested that the caffeic acid derivatives (such as echinacoside and cichoric acid) and the polysaccharides, glycoproteins, alkamides and polyacetylenes make better standards. Some of the typical dosage recommendations are listed below (McKenna et al., 2002):
•Dried root or tea – 1-2 grams, three times daily;
•Freeze-dried plant – 325-650 mg, three times daily;
•Juice of aerial portions stabilized in 22% ethanol – 2-3 mL, three times daily;
•Tincture (1:5) – 3-4 mL, three times daily;
•Fluid extract (1:1) – 1-2 mL, three times daily;
•Solid dry extract (6.5:1 or 3.5% echinacoside) 100-250 mg, three times daily.
Chronic use of Echinacea is discouraged by some sources because it is believed to loose its effectiveness at boosting the immune system when needed during long-term usage(Chua, 2003). When used at the recommended doses, side-effects from taking Echinacea are rare, and there is little or no toxicity associated with its use. The LD50 of fresh-pressed E. purpurea juice in mice is 50 mL/kg, i.v.; and the polysaccharides of the aerial portions of the plant produced an LD50 of 1,000 to 2,500 mg/kg i.p in mice. Long term administration of the fresh-pressed juice also produced no toxic effects at many times the human dose; and no significant acute or subacute toxicity was found from oral administration of up to 15 g/kg and 8 g/kg, respectively (McKenna et al., 2002).
Echinacea may interfere with drugs that have immunosuppressant effects such as cyclosporine, and corticosteroids. In vitro studies showed inhibition of 3A4 enzyme activity of the CytochromeP450 system that would suggest possible interactions with lovastatin, ketoconazole, fexofenadine, and triazolam, etc. Those taking metronidazole or disulfram should avoid due to varying alcohol contents of Echinacea preparations. The use of acetaminophen, amiodarone, methotrexate, or ketoconazole with Echinacea may possibly increase the risk of hepatotoxicity (Abebe, 2002).
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EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.