Echinacea

Plant Part Used

E. angustifolia – root ; E. purpurea – root, aerial portion succus (fresh plant juice)

Active Constituents

Caffeic acid derivatives, flavonoids, polyacetylenes, alkylamides, essential oils (humulene, caryophylene), polysaccharides.(1),(2) The health properties of Echinacea have not been found to be responsible by a single constituent; rather they appear to work synergistically.

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Echinacea, commonly called purple coneflower, has been used for centuries by Native Americans as a remedy for eye conditions, snake bites, insect stings, infected wounds, eczema, enlarged glands, pain, mumps, and rabies. In the early 20th century, Echinacea was used by a group of physicians known as the "Eclectics," whose medicinal practice relied primarily on the use of plants and their disease-healing properties. Echinacea research during the last 20 years has focused on its immune-stimulating properties.

A question of concern is should Echinacea products be consumed on a cyclical basis or is it safe to use Echinacea chronically for indefinite periods of time? The length of time to dose Echinacea has been a subject of debate for some time. The concern began following the publication of the work of Jurcic, et al.(10) The data seemed to indicate that with use of Echinacea greater than 5 days, the increase in phagocytic activity eventually returned to pretreatment levels, indicating that Echinacea may lose its effectiveness. A recent review of the data suggests its misinterpretation, noting that the levels of phagocytic activity only began declining following the discontinuation of Echinacea.(11) Several clinical studies have been completed indicating the safety of Echinacea with longer-term use. A study involving an 8-week treatment period demonstrated no significant difference in the occurrence of side effects between the Echinacea group and the placebo group.(12) Another study concluded that "adverse events on oral administration [of Echinacea] for up to 12 weeks are infrequent and consist mainly of unpleasant taste."(13) The safety of Echinacea when used for periods greater than 8 to 12 weeks has not been evaluated.

Interactions and Depletions

Drugs metabolized by cytochrome P450 hepatic enzyme system – Echinacea has been reported in laboratory studies to interact with cytochrome P450 enzyme system, therefore potentially altering the levels of drugs metabolized by this pathway.(40) Echinacea may also interact with the drug efflux transporter P-glycoprotein (P-gp).(41) Use Echinacea with caution if taking prescription mediations, especially those with narrow therapeutic window, such as digoxin, theophylline, and phenytoin.

Interactions

Dosage Info

Dosage Range

250-1,000mg (standardized extract) up to 4 times a day during flu season. Some clinicians recommend a dosing cycle such as using it 3 weeks on and 1 week off or 8 weeks on and 1 week off. Please see the introduction for a discussion regarding cyclical dosing.

Angustifolia Root Tea: For colds, drink 1 cup freshly made tea several times daily.(14)

Liquid succus: Dosages range from 6-9mL daily in divided doses, for five to seven days then 60 drops three times a day with food for 1 day, then 40 drops three times a day with food for up to 10 days.

Most Common Dosage

Acute - 500mg (standardized extract), 3 times a day for day 1 then 250mg, 4 times a day. Prevention - 250mg (standardized extract), 2 times a day, a dosing cycle may be used as indicated above.

The recommended dose of Echinacea purpurea liquid (succus) is 60 drops, 3 times a day with food for 1 day, then 40 drops, 3 times a day with food for up to 10 days.

Angustifolia Root Tea: For colds, drink 1 cup freshly made tea several times daily.

Liquid succus: 6mL daily in divided doses, for five to seven days then 60 drops three times a day with food for 1 day, then 40 drops three times a day with food for up to 10 days

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 4% echinacosides (angustifolia), 4% sesquiterpene esters (purpurea).

Echinacea purpurea (succus) should be standardized to contain not less than 2.4% soluble beta-1,2 d-5 fructofuranosides.

Uses

Frequently Reported Uses

  • Immune function
  • Upper respiratory tract Infections, including colds/influenza
Other Reported Uses
  • Anti-Inflammatory
  • Antiviral
  • Skin Disorders, including eczema
  • Wound Healing

Toxicities & Precautions

General

No known toxicity and side effects are rare.(15),(16)

Allergy

Allergic reactions to Echinacea are documented and include anaphylaxis, mild to acute asthma attacks and a maculopapular rash. Pooling patients from the author's office practice, 20% of 100 atopic subjects who had never taken Echinacea had positive skin prick testing results to Echinacea.(17)

Health Conditions

Individuals with kidney disease or acute infections should not take for longer than 10 days. Use with caution in extended periods by individuals with compromised immunity.(18)

Individuals with liver damage or at risk for liver disease should use Echinacea with caution. There has been 1 case report of acute hepatitis occurring in an individual taking Echinacea, but a cause-and-effect relationship was not proven.(43)

Individuals with gastrointestinal dysbiosis or conditions associated with gut inflammation should use Echinacea with caution. Echinacea has been reported to lead to imbalances in gastrointestinal microflora.(44)

Pregnancy/ Breast Feeding

If pregnant or nursing, consult a physician before use. A recent study of 206 women using Echinacea products during pregnancy (112 women used the herb in the first trimester) concluded that Echinacea use is not associated with an increased risk for major malformations.(19)

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Immune Function

Echinacea has non-specific stimulatory effects on the immune system.(3),(4) There have been many studies supporting Echinacea's value to the immune system, with research indicating that Echinacea may stimulate the alternate and complementary pathway and activate white blood cells to scavenge for bacteria and cellular debris.(5) Echinacea has been used to improve wound healing,(6) is reported to have antibacterial and antifungal activity,(7) and to help in the treatment of colds and influenza.(8),(9)

There are several mechanisms that could explain Echinacea’s positive activity on the immune system. Echinacea reportedly stimulates an alternate pathway for the immune system.(20) In one study, ethanolic extracts of Echinacea purpurea, E. pallida, and E. angustifolia roots were examined for immunological activity in laboratory mice.(21) In the in vivo experiment, all orally administered extracts were found to enhance phagocytosis significantly. These results correlate with the stimulation of phagocytosis in the in vitro granulocyte test.

Echinacea is reported to activate and increase white blood cell activity and cell-mediated immunity.(22),(23),(24) The components of white blood cells most affected by this are T-lymphocytes, macrophages and killer cells.(25) Cell-mediated immunity provides resistance to a variety of pathogens and guards against the development of arthritis, allergies, and other potential pathologies. A polysaccharide in Echinacea (arabinogalactan) is reported to increase interferon, tumor necrosis factor and interleukin-1 production through stimulation of macrophage activity.(26) More recent studies support Echinacea’s immune support based on alkylamides which modulate tumor necrosis factor (TNF)-alpha due to moderate to high cannabinoid receptor binding activity.(44),(45) Echinacea’s use in colds and influenza is also reported to be based on the antiviral activity by inhibiting viral growth and the secretion of pro-inflammatory cytokines.(46)

Several meta-analysis reports have been conducted over the past few years regarding the effectiveness of Echinacea preparations in the treatment and management of upper respiratory infections (URI's). A 2007 meta analysis of published evidence supports Echinacea's benefit in decreasing the incidence and duration of the common cold.(47) A 2007 Cochrane Database review looked at 16 human trials including a total of 22 comparisons of Echinacea preparations and a control group (19 placebo, 2 no treatment, 1 another herbal preparation).(48) All trials except one were double-blinded, with a variety of different Echinacea preparations and species used. The authors concluded that Echinacea preparations tested in clinical trials differ greatly, with some evidence that preparations based on the aerial parts of E. purpurea being effective for the early treatment of colds in adults, but with inconsistent results. Another 2006 meta analysis evidence suggests that standardized extracts of Echinacea are effective in the prevention of symptoms of the common cold after clinical inoculation, compared with placebo. More rigorous trials are needed.

There are some negative studies using Echinacea for colds/influenza. A 2000 study evaluating the effectiveness of Echinacea for the prevention of rhinovirus colds was conducted in 117 subjects.(27) The authors concluded that the preparation of Echinacea used in the study had no significant effect on either the occurrence of infection or the severity of illness. The study used 300mg three times a day of a 4% phenolic extract of a mixture of E. purpurea and E. angustifolia formulated as a powder and given at 300 mg three times a day. It was reported that the Echinacea preparation used in this study was analyzed by reversed-phase high-pressure liquid chromatography and was found to contain 0.16% cichoric acid with almost no echinacosides or alkamides present. Another study regarding the efficacy of E. purpurea in treating upper respiratory infections (URI's) in children also gave a negative report. The quality of the extract used is unknown.(28) It is important to use standardized quality products for the best therapeutic benefits.

A randomized controlled trial in children with recurrent otitis media found no improvement of symptoms when using an alcohol liquid extract of Echinacea purpurea.(49) The extract actually was reported have a borderline increased risk of having at least one episode of acute otitis media during 6-month follow-up compared to placebo.

A small clinical study found that Echinacea is safe and effective in the control of low-grade autoimmune idiopathic uveitis.(50)

Other Uses

Echinacea (more prominently E. angustifolia) inhibits the enzyme hyaluronidase.(32) The active constituents in Echinacea seem to inhibit the breakdown of collagen ground substance and stimulate fibroblasts to make more of the ground substance. A study reported that polyphenols (caffeoyl derivatives including echinacoside, chlorogenic acid, cichoric acid, cynarin, and caffeic acid) of Echinacea species protects collagen from free radical damage through a scavenging effect on reactive oxygen species and/or C-, N-, S-centered secondary radicals.(33) The authors concluded that there may be an indication for the topical use of extracts from Echinacea species for the prevention/treatment of photodamage of the skin by UVA/UVB radiation, in which oxidative stress plays a crucial role. Echinacea is a reported antioxidant.(34) Another small human study found that Echinacea improved immune function and prevented adverse health effects in workers exposed to ionizing radiation.(51)

The anti-inflammatory activity of a polysaccharide fraction obtained from Echinacea angustifolia roots was studied for its effects on inflammation in laboratory animals.(35) The polysaccharide fraction (when injected intravenously) almost completely inhibited the carrageenan-induced edema over 8 hours. When applied topically, it inhibited mouse ear edema induced by croton oil. The fraction also reduced the leukocytic infiltration of the croton oil dermatitis, evaluated both as peroxidase activity and histologically. After topical application, the polysaccharide fraction from Echinacea angustifolia roots appears to be slightly inferior in potency to indomethacin. The authors concluded that the anti-inflammatory activity of E. angustifolia resides in its polysaccharidic content. Also, polyunsaturated alkamides isolated from Echinacea angustifolia were reported to possess inhibitory activity in the in vitro cyclooxygenase and 5-lipoxygenase assays, making it a potential agent in inflammatory conditions.(36) Laboratory studies have also reported ethanol extracts from Echinacea purpurea roots have potent TRPV1 agonist activity.(52)  TRPV1 is a mammalian pain receptor involved in pain and inflammatory processes and is a prime therapeutic target for analgesic and antiinflammatory drugs.

A 2007 study in 24 athletes found that Echinacea administration resulted in an increase in erythropoietin (EPO) and IL-3 but did not significantly alter RBCs, hemoglobin (Hb), or hematocrit (Hct).(53) Echinacea has also been reported in in vitro studies to inhibit COX-2 dependent PGE2 formation at sites of neurogliomal inflammation.(54)

Echinacea is reported to have a wide level of antimicrobial activity on bacteria, fungi, and viruses, including herpes simplex-1.(37),(38),(55) Although in more of a traditional sense, Echinacea has been used externally for a wound wash, eczema, burns, herpes, canker sores, and abscesses, as well as other conditions.(39)

References

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  49. Wahl RA, Aldous MB, Worden KA, Grant KL. Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial. BMC Complement Altern Med. 2 Oct 2008;8:56.
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  53. Whitehead MT, Martin TD, Scheett TP, Webster MJ. The effect of 4 wk of oral Echinacea supplementation on serum erythropoietin and indices of erythropoietic status. Int J Sport Nutr Exerc Metab. Aug 2007;17(4):378-390.
  54. Hinz B, Woelkart K, Bauer R. Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells. Biochem Biophys Res Commun. 24 Aug 2007;360(2):441-446. Epub 19 Jun 2007.
  55. Ghaemi A, Soleimanjahi H, Gill P, Arefian E, Soudi S, Hassan Z. Echinacea purpurea polysaccharide reduces the latency rate in herpes simplex virus type-1 infections. Intervirology. 2009;52(1):29-34. Epub 17 Apr 2009.