Echinacea spp

Abstract and key points
  • Echinacea herbal preparations are produced from the flowering plants Echinacea purpurea, Echinacea pallida and Echinacea angustifolia.
  • Several potential uses of echinacea in cancer management have been investigated but there is currently insufficient robust evidence to support these.
  • Echinacea is generally well tolerated but little is known of its effects on anticancer drugs if given concurrently.

Echinacea (coneflower) products are herbal preparations derived from the root and above ground parts of the flowering plants Echinacea purpureaEchinacea pallida and Echinacea angustifolia. Echinacea has a long history of medicinal use and is widely used in the treatment and prevention of upper respiratory tract infections. Claims in relation to cancer are that it can boost the immune system, reduce the adverse effects of chemotherapy and radiotherapy and has some anticancer effects. In vitro studies have suggested immunostimulating and anti-cancer activity of various constituents of echinacea. However, clinical studies investigating these effects have been limited by small sample sizes, lack of a control group or use of combination products. Echinacea is generally well-tolerated with the most frequently reported adverse effects being gastrointestinal upsets and rashes. Theoretically, echinacea may interact with immunosuppressive drugs and with metabolism of drugs via the cytochrome P450 system. In summary, there is currently insufficient evidence to support or refute the claims for echinacea in relation to cancer management.

Read about the regulation, supervision and reimbursement of herbal medicine at NAFKAMs website CAM Regulation.

Document history

Assessed as up to date in January 2019 by Barbara Wider.
Assessed as up to date in February 2017 by Barbara Wider.
Assessed as up to date in April 2016 by Barbara Wider.
Assessed as up to date in January 2015 by Barbara Wider.
Minor update in April 2014 by Barbara Wider.
Most recent update and revision in October 2012 by Karen Pilkington.
Summary first published in July 2011, authored by Karen Pilkington.

Citation

Karen Pilkington, CAM-Cancer Consortium. Echinacea spp [online document]. February 8, 2017.

What is it?

Description

Echinacea species are flowering plants that belong to the Aster (Asteraceae or Compositae) family.

Names

The species most commonly used as medicinal herbs are E. purpureaE. angustifolia and E.pallida. Common names include American coneflower, coneflower, purple coneflower, pale coneflower. Brand names include Echinagard, Echinacin, Echinaforce, Echinaid1,2.

Ingredients

Several groups of active constituents have been identified: Glycoproteins, alkylamides (also known as alkamides), polysaccharides including arabinogalactan and heteroxylan, and phenolic substances – caffeic acid and related compounds such as cynarine, echinacosides, chlorogenic acid, chicoric acid1,2,3. The amount of each of the constituents found in the three species in medicinal use varies3,4.

Administration and dosage

Echinacea is most frequently taken orally. It may also be applied topically for treatment of small superficial wounds.5 Injectable preparations have been used in research studies but are not generally available and have been associated with severe reactions2. For oral administration, echinacea may be given as a tablet or capsule, as herb juice or tea, or as a tincture. Various dosages have been used depending on the formulation but these generally relate to use for the prevention or treatment of the common cold or influenza1,2 Recommended doses tend to be based on historical practice2. Use in children less than 12 is not recommended and echinacea is contra-indicated in those less than 1 year.5 Preparations (extracts and whole-plant products) are produced from the roots or above ground parts of E. purpureaE. angustifolia and E.pallida. Products available as echinacea vary in composition depending on the species, parts of the plant used and the extraction method used in production6.

History/provider(s)

Echinacea species are native to North America and were originally used as traditional herbal remedies by indigenous American populations for many different conditions2,7. European settlers learned of their medicinal use and subsequently adopted them for their own use7. Echinacea preparations continued to be used in Europe, particularly Germany7. Interest in herbs such as echinacea has increased in recent years due to increased antibiotic resistance and the limitations of anti-viral agents for common infections such as colds and flu. Echinacea preparations are prescribed by herbal practitioners but are also widely available to purchase for self-treatment. Use of echinacea for cancer is documented in texts reporting traditional use data related to the Eclectics, a group of practitioners in the United States in the late 19th and early 20th centuries8.

Claims of efficacy/Alleged indication(s)

The main claim related to echinacea is that it boosts the body’s immune system by stimulating the activity of macrophages and natural killer cells. It is promoted mainly for the treatment of infections or other conditions where stimulation of the immune system is considered to be beneficial1. These include colds, influenza, other respiratory infections, urinary tract infections, vaginal candidiasis (‘thrush’) and treatment of superficial wounds. It is also promoted as a general ‘immune-stimulant’2. Some therapists have also claimed that echinacea can help relieve adverse effects of chemotherapy and radiotherapy used in the treatment of cancer9. It has also been used in an effort to prolong survival time in patients with advanced hepatocellular carcinoma and colorectal cancer1.

Mechanism(s) of action

The exact mechanism of action for the effects of echinacea preparations on the immune system is unclear. The main action of Echinacea purpurea is considered to be stimulation of the non-specific immune system, particularly phagocytosis by macrophages and the activity of natural killer cells5. Commercial preparations of echinacea juice have been shown to increase cytokine production by macrophages10. A series of in-vitro studies have demonstrated that Echinacea purpureastimulates various immune cells including macrophages, polymorphnuclear granulocytes and natural killer cells7. Effects on T-cell and B-cell activation and proliferation are less clear. Several constituents of echinacea are considered to play a role in its effects on the immune system6,11,12,13. However, the findings from in-vitro and ex-vivo studies have not always been reflected in clinical studies14,15. Recent research suggests that the action of Echinacea purpurea varies depending on the portion of the plant used and the extraction method16.

Prevalence of use

Echinacea is one of the most widely used herbs in USA and European countries. In 2002, it was the most frequently used herb in the USA being used by over 40% of the population in the previous year17. By 2007 use had declined to approximately 20% of the population18 Use is primarily for the prevention or treatment of viral upper respiratory tract infections. A large European survey confirmed that echinacea was among the herbs used by cancer patients but the extent of use or specific reason for use was not reported19. Other surveys suggested that the main reason for use by cancer patients is to boost the immune system20,21.

Legal issues

Echinacea products are widely available in pharmacies, health food and grocery stores and on the internet. Echinacea purpurea (l.) moench, and herba recens have been adopted by the European Medicines Agency’s Committee on Herbal Medicinal Products (HMPC)5. The use of Echinacea purpurea for the short-term prevention and treatment of the common cold is classed as well-established use and the treatment of small superficial wounds as traditional use5.

Cost(s) and expenditures

Typical costs are £10 (12 Euros, US prices $12-16) for a 50ml bottle of liquid extract and £10 (12 Euros, US prices $12-16) for 60 tablets. Doses are not well-established except for use in upper respiratory tract infections.

Does it work?

Systematic reviews, meta-analyses

Systematic reviews and meta-analyses of the effectiveness of echinacea have been published but these are limited to its use in prevention or treatment of the common cold6,22,23. No systematic reviews have focused on its use in cancer patients.

Clinical trials

Several clinical trials investigated the effects of a combination product (Esberitox®) containing echinacea in the management of radiation-induced leucopenia. Few details of the early studies are available2,24,25,26.

Subsequent studies also utilised a combination product and the presence of other herbs in the preparations complicates the interpretation of the findings with respect to echinacea27-29.

A more recent open prospective study with matched historical controls tested whether a polysaccharide fraction isolated fromEchinacea purpurea reduced unwanted effects of chemotherapy30. Fifteen patients with advanced gastric cancer received daily intravenous injections of the polysaccharide fraction for 10 days starting 3 days before the start of palliative chemotherapy. After treatment, the median number of leucocytes was significantly greater than that in the control group. No clinically relevant effects on phagocytic activity or lymphocyte subpopulations were observed. Adverse events including two deaths were reported but these were considered likely to be due to chemotherapy or the patients’ overall health condition. It is difficult to draw firm conclusions on beneficial or adverse effects due to the small sample size of the study and lack of a concurrent control group.

Case series/studies

Only a few attempts to investigate echinacea’s role as an anti-cancer agent have been made. Preliminary studies have investigated the anti-cancer effects of Echinacea purpurea extracts combined with chemotherapy in patients with advanced metastatic colorectal cancer who had received surgery and/or chemotherapy were treated with the extract (Echinacin®) plus cyclophosphamide and thymostimulin31. The treatment appeared well-tolerated but no major beneficial effects resulted and survival times corresponded to those expected for untreated patients.7 Similar studies were conducted in small numbers of patients with advanced pancreatic cancer and hepatocellular cancer32,33,34. All studies were reported between 1990 and 1994.

Pre-clinical studies

As described under Mechanism of Action, several constituents of echinacea (heteroxylan, arabinogalactan, cichoric acid, echinacosides) have been shown in in-vitro, in-vivo and ex-vivo studies to induce changes in immune parameters. However, there is no evidence that these activities translate to beneficial outcomes in oncology. A diene olefin isolated from Echinacea angustifolia and Echinacea pallida root oils was reported to have antitumour activity in 197235. A subsequent in vitro study appeared to indicate that root extracts from the three commonly used species of echinacea reduced cancer cell viability and induced apoptosis36. A further in vitro study showed Echinacea purpurea flower extract and cichoric acid to have a growth-inhibitory effect against colon cancer cells47. Research interest has focused on acetylenes present in Echinacea pallidaextract and alkamides isolated from Echinacea angustifolia37,38,39.

Is it safe?

Adverse events

Safety data mainly derived from clinical trials and single case reports indicates that echinacea is generally well-tolerated40. Most frequently reported adverse effects include gastro-intestinal upsets and rashes41,20. Individuals with atopia or sensitivity to the Asteraceae/Compositae plant family might be at increased risk of allergic reactions (urticaria, bronchospasm and anaphylaxis).41 Administration of echinacea by injection has been associated with shivering, fever and muscle weakness1,42. Echinacea has been implicated as a possible causative agent in joint and muscle pain, liver-related problems such as raised liver enzymes and hepatitis, and Sjögren’s syndrome but this causality has not been confirmed and these have been reported only rarely1,42.

Short-term treatment with echinacea has been assessed as likely to be safe as several forms of echinacea have been used apparently safely in trials lasting up to 12 weeks1. The EMEA recommends treatment durations for the common cold and for topical treatment of wounds of not more than 10 days and not more than a week respectively5. Duration of treatment for other indications is unclear and there is insufficient reliable evidence about the safety of long-term treatment with echinacea1.

Contraindications/Warnings

Use of echinacea purpurea juice has been assessed as possibly safe if used orally short-term in children from 2 to 11 years of age1. However, it may increase the risk of rash in some children. The EMEA does not recommend the use in children and states that use below 1 year of age is contra-indicated5.

There are limited data on the safety of echinacea in pregnancy: it is insufficient to draw firm conclusions and data on the effect on the immune system of the newborn child are not available1,42. Similarly, there is insufficient reliable information on its use in breast feeding1. The EMEA recommends that echinacea should be avoided in pregnancy and while breast feeding5. The EMEA also recommends that, because of its immunostimulating activity, echinacea should not be used in cases of progressive systemic disorders, autoimmune diseases, immunodeficiencies, immunosuppression and diseases of the white blood cell system5.

Interactions

Echinacea appears to inhibit CYP1A2 enzymes in humans and so in theory might increase levels of drugs metabolised by CYP1A21. These include paracetamol, amitriptyline, diazepam, oestradiol, ondansetron, propranolol, theophylline, warfarin and others.

Preliminary evidence suggests that echinacea inhibits intestinal CYP3A4 and induces hepatic CYP3A4 enzymes1. It is unclear how this is likely to affect drugs metabolized by CYP3A4. These include lovastatin, clarithromycin, cyclosporine, oestrogens and others. A case has been reported of a probable interaction between cytotoxic drug, etoposide, and Echinacea which resulted in trombocytopenia requiring a pplatelet transfusion45.

Echinacea purpurea did not significantly alter the pharmacokinetics of the CYP3A4 substrate docetaxel in a study of ten cancer patients receiving 135 mg, 60 min IV infusion of docetaxel before intake of a commercially available E. purpurea extract (20 oral drops three times daily) and 3 weeks later after a 14 day supplementation period with E. purpurea47.

As echinacea has immuno-stimulating activity, in theory it may interfere with immunosuppressant treatment1.

Quality issues

Products available as echinacea vary in composition depending on the species, parts of the plant used and the extraction method used in production6. Some manufacturers standardise echinacea extracts according to echinacoside content while others standardise to chicoric acid2. Analysis of a range of echinacea products, however, revealed that many were mislabelled, contained substances other than the herb or actually contained no echinacea43,44. Quality of echinacea products will depend at least partially on the regulatory standards and good manufacturing requirements in the country in which the product is manufactured.

References
  1. Natural Medicines Comprehensive Database: professional version. Echinacea monograph. Stockton (CA): Therapeutic Research Faculty. Available online. Accessed 8 February 2017.
  2. Natural Standard: the authority on integrative medicine. Echinacea monograph. Cambridge(MA): Natural Standard. 2008
  3. Sloley BD, Urichuk LJ, Tywin C, Coutts RT, Pang PK, Shan JJ. Comparison of chemical components and antioxidants capacity of different Echinacea species. J Pharm Pharmacol. 2001 Jun;53(6):849-57.
  4. Barnes J, Anderson LA, Gibbons S, Phillipson JD. Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt.,Echinacea purpurea (L.) Moench): a review of their chemistry, pharmacology and clinical properties. J Pharm Pharmacol. 2005 Aug;57(8):929-54.
  5. European Medicines Agency. Committee on Herbal Medicinal Products (HMPC): Community herbal monograph on Echinacea purpurea (l.) moench, herba recens. London: European Medicines Agency. 2008.
  6. Linde K, Barrett B, Wölkart K, Bauer R, Melchart D. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD000530.
  7. Barrett B. Medicinal properties of Echinacea: a critical review. Phytomedicine 203; 66-86, 2004.
  8. Mills S and Bone K. Echinacea. In: Principles and practice of phytotherapy: modern herbal medicine. London: Churchill Livingstone. 2000.
  9. Cancer Research UK. Cancerhelp UK: Echinacea information page. 2009. Available online. Accessed February 8 2017.
  10. Burger RA, Torres AR, Warren RP, Caldwell VD, Hughes BG. Echinacea-induced cytokine production by human macrophages. Int J Immunopharmacol. 1997 Jul;19(7):371-9.
  11. Stimpel M, Proksch A, Wagner H, Lohmann-Matthes ML.Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect Immun. 1984 Dec;46(3):845-9.
  12. Luettig B, Steinmüller C, Gifford GE, Wagner H, Lohmann-Matthes ML. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. Natl Cancer Inst. 1989 May 3;81(9):669-75.
  13. Gertsch J., Schoop R., Kuenzle U. and Suter A.: Echinacea alkylamides modulate TNF-α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Letters 2004 577 (3):563-569.
  14. Schwarz E, Metzler J, Diedrich JP, Freudenstein J, Bode C, Bode JC.Oral administration of freshly expressed juice of Echinacea purpurea herbs fail to stimulate the nonspecific immune response in healthy young men: results of a double-blind, placebo-controlled crossover study.J Immunother. 2002 Sep-Oct;25(5):413-20.
  15. Schwarz E, Parlesak A, Henneicke-von Zepelin HH, Bode JC, Bode C.Effect of oral administration of freshly pressed juice of Echinacea purpurea on the number of various subpopulations of B- and T-lymphocytes in healthy volunteers: results of a double-blind, placebo-controlled cross-over study. Phytomedicine. 2005 Sep;12(9):625-31.
  16. Benson JM, Pokorny AJ, Rhule A, Wenner CA, Kandhi V, Cech NB, Shepherd DM. Echinacea purpurea extracts modulate murine dendritic cell fate and function. Food Chem Toxicol. 2010 May;48(5):1170-7. Epub 2010 Feb 10.
  17. Barnes P, Powell-Griner E, McFann K, Nahin R. CDC Advance Data Report #343. Complementary and Alternative Medicine Use Among Adults: United States, 2002. May 27, 2004.
  18. Barnes PM, Bloom B, Nahin R. CDC National Health Statistics Report #12. Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007. December 10, 2008
  19. Molassiotis A, Fernadez-Ortega P, Pud D, Ozden G, Scott JA, Panteli V, Margulies A, Browall M, Magri M, Selvekerova S, Madsen E, Milovics L, Bruyns I, Gudmundsdottir G, Hummerston S, Ahmad AM, Platin N, Kearney N, Patiraki E. Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol. 2005 Apr;16(4):655-63. Epub 2005 Feb 2.
  20. Engdal S, Steinsbekk A, Klepp O, Nilsen OG. Herbal use among cancer patients during palliative or curative chemotherapy treatment in Norway. Support Care Cancer. 2008 Jul;16(7):763-9. Epub 2008 Jan 15.
  21. Werneke U, Earl J, Seydel C, Horn O, Crichton P, Fannon D. Potential health risks of complementary alternative medicines in cancer patients. Br J Cancer. 2004 Jan 26;90(2):408-13.
  22. 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 Jul;7(7):473-80. Review. Erratum in: Lancet Infect Dis. 2007 Sep;7(9):580.
  23. Schoop R, Klein P, Suter A, Johnston SL. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis. Clin Ther. 2006 Feb;28(2):174-83.
  24. Pohl P. CCT [On the therapy of irradiation-induced leukopenia with Esberitox]. Med Klin. 1969;64(35):1546-7.
  25. Pohl P. [Treatment of radiation-induced leukopenia with Esberitox]. Ther Ggw 1970;109(6):902-906.
  26. Sartor KJ. [Efficacy of Esberitox in the treatment of radiation-induced leukopenia]. Ther Ggw 1972;111(8):1147-1150.
  27. Bendel R, Bendel V, Renner K, et al. [Supplementary treatment with Esberitox of female patients undergoing curative adjuvant irradiation following breast cancer]. Strahlenther Onkol 1988;164(5):278-283.
  28. Bendel R, Bendel V, Renner K, et al. [Additional treatment with Esberitox N in patients with chemo- radiotherapy treatment of advanced breast cancer]. Onkologie. 1989;12 Suppl 3:32-38.
  29. Elsasser-Beile U, Willenbacher W, Bartsch HH, Gallati H, Schulte MJ, von KS. Cytokine production in leukocyte cultures during therapy with Echinacea extract. Journal of Clinical Laboratory Analysis 1996;10(6):441-5.
  30. Melchart D, Clemm C, Weber B, Draczynski T, Worku F, Linde K, et al. Polysaccharides isolated from Echinacea purpurea herba cell cultures to counteract undesired effects of chemotherapy - a pilot study. Phytotherapy Research 2002;16(2):138-42.
  31. Lersch C, Zeuner M, Bauer A, Siemens M, Hart R, Drescher M, et al. Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea extracts (echinacin) in patients with far advanced colorectal cancers: preliminary results. Cancer Investigation 1992;10(5):343-8.
  32. Lersch C, Zeuner M, Bauer A, Hart R, Wagner F, Siebenrock K, et al. Palliative chemoimmunotherapy with low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (echinacin) and thymostimulin in outpatients with far advanced pancreatic malignancies. A preliminary report. Journal of Experimental and Clinical Cancer Research 1990;9(4):247-50.
  33. Lersch C, Zeuner M, Bauer A, Berdel WE, Drescher WE, Hart R, et al. Stimulation of immunocompetent cells in patients with gastrointestinal tumors during an experimental therapy with low doses of cyclophosphamide (LDCY), thymostimulin and echinaceae purpureae extracts (Echinacin). Tumor Diagnostik und Therapie 1992;13(3):115-20.
  34. Lersch C, Zeuner M, Bauer A, Siebenrock K, Hart R, Wagner F, et al. Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), Echinacea purpurea extracts (echinacin) and thymostimulin. Archiv fur Geschwulstforschung 1990;60(5):379-83.
  35. Voaden DJ, Jacobson M. Tumor Inhibitors. 3. Identification and Synthesis of an Oncolytic Hydrocarbon from American Coneflower Roots. J Med Chem 1972 15: 619-623.
  36. Chicca A, Adinolfi B, Martinotti E, Fogli S, Breschi MC, Pellati F, Benvenuti S, Nieri P. Cytotoxic effects of Echinacea root hexanic extracts on human cancer cell lines. J Ethnopharmacol. 2007 Mar 1;110(1):148-53. Epub 2006 Sep 23.
  37. Chicca A, Adinolfi B, Pellati F, Orlandini G, Benvenuti S, Nieri P. Cytotoxic activity and G1 cell cycle arrest of a Dienynone from Echinacea pallida. Planta Med. 2010 Mar;76(5):444-6. Epub 2009 Oct 20.
  38. Chicca A, Raduner S, Pellati F, Strompen T, Altmann KH, Schoop R, Gertsch J. Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts. Int Immunopharmacol. 2009 Jul;9(7-8):850-8. Epub 2009 Mar 19.
  39. Chicca A, Pellati F, Adinolfi B, Matthias A, Massarelli I, Benvenuti S, Martinotti E, Bianucci AM, Bone K, Lehmann R, Nieri P. Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida. Br J Pharmacol. 2008 Mar;153(5):879-85. Epub 2008 Jan 14.
  40. Huntley A.L., Thompson Coon J. and Ernst E.: The safety of herbal medicinal products derived from echinacea species: a systematic review. Drug Saf. 2005; 28(5):387-400.
  41. Jeschke E, Ostermann T, Lüke C, Tabali M, Kröz M, Bockelbrink A, Witt CM, Willich SN, Matthes H. Remedies containing Asteraceae extracts: a prospective observational study of prescribing patterns and adverse drug reactions in German primary care. Drug Saf. 2009;32(8):691-706. doi: 10.2165/00002018-200932080-00007.
  42. Engdal S, Steinsbekk A, Klepp O, Nilsen OG. Herbal use among cancer patients during palliative or curative chemotherapy treatment in Norway. Support Care Cancer. 2008 Jul;16(7):763-9. Epub 2008 Jan 15.
  43. Perri D, Dugoua JJ, Mills E, Koren G. Safety and efficacy of Echinacea (Echinacea angustafolia, E. purpurea and E. pallida) during pregnancy and lactation. Can J Clin Pharmacol 2006 13(3): 262-267.
  44. Gilroy CM, Steiner JF, Byers T, et al. Echinacea and truth in labeling. Arch Intern Med 2003;163:699-704.
  45. Chardonnet CO, Charron CS, Sams CE, Conway WS. Screening of Nine Echinacea Supplements for Antitumor Activity Using the Potato Disc Bioassay. Journal of Herbs, Spices and Medicinal Plants 2006;12(1-2):107-16. Labeling issues
  46. Bossaer JB, Odle BL. Probable etoposide interaction with Echinacea. J Diet Suppl 2012; 9(2): 90-95.
  47. Tsai YL, Chiu CC, Yi-Fu Chen J, Chan KC, Lin SD. Cytotoxic effects of Echinacea purpurea flower extracts and cichoric acid on human colon cancer cells through induction of apoptosis. J Ethnopharmacol 2012;143(3):914-9.48.
  48. Goey AK, Meijerman I, Rosing H, Burgers JA, Mergui-Roelvink M, Keessen M, Marchetti S, Beijnen JH, Schellens JH. The effect of Echinacea purpurea on the pharmacokinetics of docetaxel. Br J Clin Pharmacol 2013; 76(3):467-74.

CAM Cancer is hosted by NAFKAM

Norway's National Research Center in Complementary and Alternative Medicine

Les mer om NAFKAM

Other websites from NAFKAM: