Echinacea

• How It Works

  Echinacea does not appear to prevent the common cold, but it may shorten the duration of colds or be of benefit in the early treatment of influenza when taken within 24–48 hours of the first symptoms.

  Echinacea extract appears to stimulate immune cells in laboratory and animal studies. Some compounds found in echinacea appear to reduce inflammation, relieve pain, and kill bacteria and viruses directly. Human studies have found that echinacea is not effective for preventing the common cold or to treat respiratory infections, but it may shorten the duration of colds. One large clinical trial suggested a specific echinacea formulation was as effective as  a prescription drug to treat influenza, with fewer side effects.

  Few studies have been conducted on echinacea with respect to cancer or cancer treatment. Some studies suggest that echinacea could alter the effectiveness of some anticancer drugs or cause adverse effects.

• Purported Uses
  • To treat the common cold
    Most studies do not support this use. One clinical trial supports the use of echinacea for reducing the length of colds, but not the severity of symptoms. One large trial suggests a specific echinacea formulation could be as effective as a prescription drug to treat influenza, with fewer side effects.
  • As an antiseptic
    Laboratory studies suggest that echinacea has antibacterial qualities.
  • To stimulate the immune system
    Laboratory and animal studies suggest that echinacea extracts stimulate different parts of the immune system. Human studies suggest immune-changing effects.
  • To treat viral infections
    Laboratory studies suggest that echinacea has antiviral properties and a human study suggests a specific echinacea formulation could be as effective as a prescription drug to treat the influenza virus.
  • For faster wound healing
    Animal models suggest wound-healing properties, but studies have not been conducted in humans.
• Do Not Take If
  • You are taking immunosuppressants (eg, tacrolimus, cyclosporine): Echinacea may lessen their effect.
  • You are taking drugs that are substrates of cytochrome P450: Echinacea may increase the risk of side effects of these drugs.
  • You are taking tamoxifen: Lab studies suggest echinacea may weaken the effects of tamoxifen.
  • You are taking etoposide: Echinacea caused low blood platelets in a patient receiving etoposide.
  • You are taking P-glycoprotein (P-gp) substrate drugs: Lab studies suggest echinacea could alter effectiveness of some of these drugs.
  • You are taking oseltamivir: Lab studies showed that echinacea reduced the active formation of this drug, and may therefore reduce effectiveness.
  • You are undergoing eyelid surgery: Echinacea increases the risk of dry eye syndrome.
  • You have allergies or asthma: Allergic reactions have been reported with echinacea.
  • You are pregnant or nursing: Echinacea has not been adequately studied in pregnant women.
• Side Effects

  Common: Headache, dizziness, nausea, constipation, mild stomach pain, skin rash, irritation

  Rare: Serious allergic reactions

  Case Reports – Oral
  Worsening of a chronic blistering skin disease: In a 55-year-old man with a history of pemphigus vulgaris, which was controlled with immunosuppressants. Only partial remission was reported after he was treated again with immunosuppressants.

  Reduced white blood cell count: In a 51-year-old woman following chronic use of echinacea. Her white blood cell count returned to normal levels 7 months after discontinuing echinacea supplements.

  Severe hepatitis: In a 45-year-old man who complained of fatigue and jaundice lasting one week, linked to daily high doses of echinacea used to strengthen his immune system after catching the cold.

  Increased eosinophil count in the bloodstream: In a 58-year-old man, there was an increase in this type of white blood cell following use of echinacea. His symptoms improved after discontinuing echinacea.

  Low platelet and blood-coagulation disorders: Two case reports involve a 61-year-old cancer patient whose use of echinacea likely interacted with etoposide, and a 32-year-old man who used echinacea to alleviate respiratory symptoms.

  Severe acute liver failure: In a 2-year-old girl, likely cause by echinacea toxicity.

  Case Report – Topical
  Eye irritation and conjunctivitis: 7 reports following use of topical echinacea were received by The National Registry of Drug-Induced Ocular Side Effects. Symptoms resolved after discontinuing echinacea.

• Special Point

  Echinacea supplements available in stores contain varying amounts and different species of echinacea. Therefore, the beneficial results seen with echinacea in clinical trials may not apply to a product that contains a different species or quality of this herb. One study found that about half of the echinacea brands tested did not contain the type or quality of echinacea that they claimed on the label.

• Brand Name

  Echinagard®, Echinacin®, Echinaforce® Hotdrink

• Scientific Name

  Echinacea purpurea, Echinacea angustifolia, Echinacea pallida

• Clinical Summary

  The genus Echinacea belongs to the family Compositae, commonly referred to as the sunflower family. Of the known species, E. purpurea, E. angustifolia, and E. pallida are commonly used in herbal medicine. Extracts derived from the root and aerial parts are widely used in Europe and the United States as nonspecific immunostimulants and to prevent or treat the common cold and influenza. However, natural products differ greatly in composition ⁽²⁶⁾, mainly due to the use of different species, variable plant materials or extraction methods, and the addition of other components. In vitro and in vivo studies suggest immunostimulatory and anti-inflammatory effects ⁽²⁷⁾. A standardized echinacea preparation inactivated influenza viruses ⁽²⁸⁾ and may improve respiratory activity ^(2) (3). In animal models, echinacea stimulated erythropoiesis, increased blood-oxygen transport ^(29) (30), produced anxiolytic effects ⁽³¹⁾, and exhibited wound-healing properties ^{(32) (33) (34)}.

  Clinical data indicate that echinacea is ineffective in preventing the common cold caused by rhinoviruses ⁽⁴⁾ or in treating upper respiratory infections ^{(5) (6) (16)}. Studies of its ability to reduce incidence and duration of the common cold yielded mixed results ^{(7) (8) (9) (10) (22) (35) (36)}. Other analyses do not indicate any benefits for treating colds, and weak evidence for a prophylactic benefit ^(26) (37), but a large randomized trial found an echinacea formulation to be as effective as oseltamivir for influenza, and with fewer adverse events in the echinacea group ⁽³⁸⁾. Small studies have shown that a standardized echinacea root extract has immunomodulating activity ⁽³⁹⁾; and an echinacea/sage spray was useful in treating acute sore throats ⁽¹⁷⁾. Preliminary data on improving or enhancing athletic performance are mixed ^(40) (41). But a topical echinacea extract was reported effective in alleviating symptoms associated with atopic eczema ⁽⁶³⁾. Echinacea may also have anticancer potential evidenced by the cytotoxic effects exerted by an extract and a major compound, cichoric acid, in human colon cancer cells ⁽⁴²⁾.

  Some studies suggest that echinacea could decrease plasma levels, affect therapeutic efficacy, or cause adverse effects with some anticancer drugs ^(25) (43). In HIV-infected patients, co-administration with etravirine was found to be safe and well tolerated ⁽⁴⁴⁾. In a large population-based study, use of echinacea was associated with a slight increase in diastolic blood pressure ⁽⁴⁵⁾. There is insufficient evidence regarding the efficacy and safety of echinacea during pregnancy ⁽⁴⁶⁾.

• Purported Uses
  • Common cold
  • Immunostimulation
  • Viral infections
  • Wound healing
• Mechanism of Action

  Echinacea’s active constituents include cichoric and caftaric acids, polysaccharides, and alkylamides ⁽⁴⁷⁾. Immune-modulating effects of a standardized echinacea root extract include upregulation of interleukin (IL)-2 and IL-8 and downregulation of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha and IL-6 ⁽³⁹⁾. Immunemodulation by alkylamides occurs through binding to human cannabinoid receptors 1 and 2, and by inhibiting TNF-alpha ⁽⁴⁸⁾. Alkylamides may also be responsible for anti-inflammatory effects ⁽²⁷⁾. Although echinacea does not appear to have significant ergogenic or anabolizing effects, it appears to enhance the immune system and decrease oxidative damage ⁽⁴⁹⁾.

  In vitro and in vivo, echinacea extracts were shown to stimulate phagocytosis, enhance mobility of leukocytes, stimulate TNF and IL-1 secretion from macrophages and lymphocytes, and improve respiratory activity ^(2) (3). However, their effects on innate immunity such as phagocytosis could not be confirmed, and showed only minimal effects on tumor progression, although echinacea did stimulate natural killer cell activity ⁽⁵⁰⁾. Other studies suggest that bacterial components of echinacea are responsible for immune benefits, as total bacterial load differences and content of bacterial lipopolysaccharides within echinacea samples have correlated with NF-kappaB activation in THP-1 cells ⁽⁵¹⁾.

  In human colon cancer cells, cichoric acid decreased telomerase activity and induced apoptosis via DNA fragmentation, caspase-9 activation, poly-ADP-ribose polymerase (PARP) cleavage and beta-catenin downregulation ⁽⁴²⁾. Differential effects of echinacea on intestinal and hepatic CYP3A activities may be due to systemic unavailability of locally-acting constituents that inhibit CYP3A, or rapid absorption of these constituents that limits intestinal exposure and CYP3A induction, or a systemically-formed constituent metabolite that is capable of inducing hepatic but not intestinal CYP3A ⁽⁵²⁾.

• Contraindications
  • Patients undergoing chemotherapy should use caution with echinacea, as it may reduce the efficacy of some anticancer medications or cause adverse effects ^{(25) (43) (53)}.
  • Patients with allergies or asthma should exercise caution with echinacea, as allergic reactions have been reported ⁽⁵⁴⁾.
  • Patients undergoing blepharoplasty (eyelid surgery), should avoid echinacea because of added increased risk of dry eye syndrome ⁽⁵⁵⁾.
• Adverse Reactions

  Common: Headache, dizziness, nausea, constipation, gastrointestinal upset, rash ^{(5) (11) (12) (54)}
  Rare: Dermatitis, anaphylaxis ^(13) (54)

  Case Reports – Oral
  Profound thrombocytopenia: In a 61-year-old man with nonsmall cell lung cancer who was concurrently taking echinacea while receiving chemoradiation with cisplatin and etoposide ⁽²⁵⁾.
  Severe thrombotic thrombocytopenic purpura (TTP): In a 32-year-old man following ingestion of echinacea to alleviate upper respiratory tract infection symptoms. TTP resolved after treatment for a month ⁽¹⁸⁾.
  Pemphigus vulgaris exacerbation: In a 55-year-old man with a history of the condition which was controlled with immunosuppressants. Exacerbation was linked to consumption of echinacea, and only partial remission was regained after he was treated again with immunosuppressants ⁽¹⁹⁾.
  Asymptomatic leukopenia: In a 51-year-old woman following chronic use of echinacea. Her white blood cell count returned to normal levels 7 months after discontinuing echinacea supplements ⁽²⁰⁾.
  Severe acute hepatitis: In a 45-year-old man who complained of fatigue and jaundice lasting one week, linked to the ingestion of daily high doses of echinacea used to strengthen his immune system after catching the cold ⁽²³⁾.
  Severe acute liver failure: In a 2-year-old girl, likely secondary to echinacea toxicity ⁽⁵⁶⁾.
  Hypereosinophilia: In a 58-year-old man following echinacea consumption, with symptoms improving after discontinuing echinacea ⁽²⁴⁾.
  Bilateral central facial palsy and severe quadriparesis: In a 25 year-old male after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. Symptoms improved after conventional treatment ⁽⁶⁴⁾.
  Acute cholestatic hepatitis: In a 41-year-old man following consumption of echinacea to strengthen immune system. His condition improved after discontinuing its use ⁽⁶⁵⁾.

  Case Reports – Topical
  Eye irritation and conjunctivitis: 7 reports following use of topical echinacea were received by The National Registry of Drug-Induced Ocular Side Effects. Symptoms resolved after discontinuing echinacea ⁽²¹⁾.

• Herb-Drug Interactions

  Cytochrome P450 substrates: Echinacea inhibits CYP3A4 ^(14) (43) and CYP2C8 ⁽⁶⁶⁾ and can affect the intracellular concentration of drugs metabolized by this enzyme.

  Cytochrome P3A or CYP1A2 substrate drugs: Caution should be used when echinacea is coadministered with drugs dependent on CYP3A or CYP1A2 for their elimination ⁽⁵⁷⁾.

  Tamoxifen: In vitro studies suggest concurrent echinacea use may result in subtherapeutic systemic exposure of prodrugs such as tamoxifen, reducing their efficacy ⁽⁴³⁾.

  Docetaxel: In a study of cancer patients receiving docetaxel, echinacea at the recommended dosage did not significantly alter docetaxel pharmacokinetics ^(58) (59).

  Etoposide: Echinacea caused profound thrombocytopenia in a patient receiving etoposide, likely due to the inhibition of CYP3A4 ⁽²⁵⁾.

  P-glycoprotein (P-gp) substrate drugs: In vitro, echinacea has been shown to inhibit P-gp activity ⁽⁶⁰⁾, but the clinical significance of this is uncertain as echinacea supplementation in humans did not affect digoxin pharmacokinetics ⁽⁶¹⁾.

  Oseltamivir: In vitro, echinacea reduced the formation of the active drug and may therefore reduce efficacy, but clinical significance is as yet undetermined ⁽⁶²⁾.

  Immunosuppressants: Echinacea may antagonize the effects of immunosuppressants ⁽¹⁹⁾.

• References

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  2. Melchart D, Clemm C, Weber B, et al. Polysaccharides isolated from Echinacea purpurea herba cell cultures to counteract undesired effects of chemotherapy-a pilot study. Phytotherapy Res 2002;16:138-42.

  3. Groom SN, Johns T, Oldfield PR. The potency of immunomodulatory herbs may be primarily dependent upon macrophage activation. J Med Food. Mar 2007;10(1):73-79.

  4. Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An Evaluation of Echinacea angustifolia in Experimental Rhinovirus Infections. N Engl J Med. 2005;353(4):341-348.

  5. Taylor JA, Weber W, Standish L, et al. Efficacy and Safety of Echinacea in Treating Upper Respiratory Tract Infections in Children: A Randomized Controlled Trial. JAMA 2003;290:2824-30.

  6. Yale SH, Liu K. Echinacea purpurea Therapy for the Treatment of the Common Cold. Arch Intern Med. 2004;164:1237-1241.

  7. Shah SA, Sander S, White CM, Rinaldi M, Coleman CI. Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis. Lancet Infect Dis 2007;7(7):473-80.

  8. Schulten B, Bulitta M, Ballering-Bruhl B, Koster U, Schafer M. Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomized, double-blind clinical trial. Arzneimittelforschung 2001;51:563-8.

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  12. Grimm W, Muller HH. A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infections. Am J Med 1999;106:138-43.

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  17. Schapowal A, Berger D, Klein P, Suter A. Echinacea/sage or chlorhexidine/lidocaine for treating acute sore throats: a randomized double-blind trial. Eur J Med Res. 2009 Sep 1;14(9):406-12.

  18. Liatsos G, Elefsiniotis I, Todorova R, Moulakakis A. Severe thrombotic thrombocytopenic purpura (TTP) induced or exacerbated by the immunostimulatory herb Echinacea. Am J Hematol. 2006 Mar;81(3):224.

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  28. Pleschka S, Stein M, Schoop R, et al. Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian influenza virus (H5N1, H7N7) and swine-origin H1N1 (S-OIV). Virol J. 2009;6:197.

  29. Goel V, Chang C, Slama JV, et al. Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats. Int Immunopharmacol. Feb 2002;2(2-3):381-387.

  30. O’Neill W, McKee S, Clarke AF. Immunological and haematinic consequences of feeding a standardised Echinacea (Echinacea angustifolia) extract to healthy horses. Equine Vet J. May 2002;34(3):222-227.

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