Echinacea spp | Cam-Cancer

Echinacea spp

Abstract and key points

Echinacea (coneflower) products are herbal preparations derived from the root and above ground parts of the flowering plants Echinacea purpurea, Echinacea 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 support 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. Clinical studies investigating these effects have been limited by small sample sizes, lack of a control group or use of combination Products.

Supportive care
• Prevention of treatment-related adverse effects: no convincing evidence exists

Antitumour treatment
• No convincing evidence exists of an effect on survival time.

Echinacea is generally well-tolerated with the most frequently reported adverse effects being gastrointestinal upsets and rashes. It is recommended that use is avoided in children under 12 years, during pregnancy and lactation and it is used with caution in those with allergies. Theoretically, echinacea may interact with immunosuppressive drugs and with metabolism of drugs via the cytochrome P450 system.

Citation

Karen Pilkington, CAM-Cancer Consortium. Echinacea spp [online document], http://cam-cancer.org/en/echinacea. November, 2021.

Document history

Fully updated and revised in October 2021 by Karen Pilkington.
Assessed as up to date in January 2019, February 2017, April 2016, January 2015 and April 2014 by Barbara Wider.
Updated and revised in October 2012 by Karen Pilkington.
Summary first published in July 2011, authored by Karen Pilkington.

What is it?

Description

Echinacea species are flowering plants that belong to the Aster (Asteraceae or Compositae) family. The species most commonly used as medicinal herbs are E. purpurea, E. angustifolia and E.pallida. Common names include American coneflower, coneflower, purple coneflower, pale coneflower. Brand names include Echinagard, Echinacin, Echinaforce, Echinaid (NMD 2021).

Background and prevalence

Echinacea species are native to North America and were originally used as traditional herbal remedies by indigenous American populations for many different conditions (Barrett 2003). European settlers adopted them for their own medicinal use (Barrett 2003). Subsequently, echinacea preparations were also used in Europe, particularly in Germany (Barrett 2003).

Echinacea is one of the most widely sold herbs in the USA and European countries. In 2002, it was the most frequently used herb in the USA but, by 2007, use declined (Barnes 2004; Barnes 2008). A further significant decline was revealed in a 2012 survey (to 0.9% of those who had used nonvitamin, nonmineral dietary supplements during the past 30 days) (Clarke 2015). Use is primarily for the prevention or treatment of viral upper respiratory tract infections. In recent years, interest in herbs such as echinacea has increased due to increased antibiotic resistance and the limitations of anti-viral agents for common infections such as colds and flu. Most recently, the focus has been on whether it has potential as an adjuvant symptomatic therapy for Covid-19 (Silveira 2020).

For cancer, use of echinacea 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 centuries (Mills 2000).  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 reported (Molassiotis 2005). A UK survey indicated use by 4% of cancer patients (Damery 2011) while other surveys suggested that the main reason for use by cancer patients is to strengthen the immune system (Engdal 2008, Werneke 2004). More recent data is not available.

Administration and dosage

Echinacea preparations are prescribed by herbal practitioners but are also widely available to purchase for self-treatment. Echinacea is most frequently taken orally. Echinacea purpurea may also be applied topically for treatment of small superficial wounds based on traditional use (EMA 2015). 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 influenza (NMD 2021). Recommended doses tend to be based on historical practice (NMD 2021). Use of Echinacea in children under 12 is not recommended, while it is contra-indicated in those less than 1 year (EMA 2015). Preparations (extracts and whole-plant products) are produced from the roots or above ground parts of E. purpurea, E. 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 production (Karsch-Volk 2014).

Alleged indications

The main claim related to echinacea is that it strengthens 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 beneficial (NCCIH 2021). These include colds, influenza, other respiratory infections, urinary tract infections, vaginal candidiasis (‘thrush’) and treatment of superficial wounds.

Mechanism of action

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 acid (NMD 2021, Sloley 2001). The amount of each of the constituents found in the three species in medicinal use varies (Sloley 2001, Barnes 2005).

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 cells (EMA 2015). Commercial preparations of echinacea juice have been shown to increase cytokine production by macrophages (Burger 1997). A series of in-vitro studies have demonstrated that Echinacea purpurea stimulates various immune cells including macrophages, polymorphnuclear granulocytes and natural killer cells (Barrett 2003). 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 system (Stimpel 1984, Luettig 1989, Gertsch 2004) and further studies have reported on adaptive and innate immune function (Karsch-Volk 2014). However, the findings from in-vitro and ex-vivo studies have not always been reflected in clinical studies (Schwarz 2002, Schwarz 2005). The action of Echinacea purpurea also appears to vary depending on the portion of the plant used and the extraction method (Benson 2010).
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 (Voaden 1972). 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 apoptosis (Chicca 2007). A further in vitro study showed Echinacea purpurea flower extract and cichoric acid to have a growth-inhibitory effect against colon cancer cells (Tsai 2012).

Legal issues and costs

Echinacea products are widely available in pharmacies, health food and grocery stores and on the internet. Echinacea purpurea (L.) and herba recens have been adopted by the European Medicines Agency’s Committee on Herbal Medicinal Products (HMPC) (EMA 2015). 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 use (EMA 2015). Echinacea pallida and angustifolia are adopted for prevention and treatment of the common cold only and based on traditional use (EMA 2012; EMA 2018).

Prices for echinacea products available over the internet vary greatly. Typical costs are 5-12 Euros for a 100ml bottle of liquid extract and 5-12 Euros for 60 tablets. Doses are not well-established except for use in upper respiratory tract infections.

Does it work?

Systematic reviews and meta-analyses of the effectiveness of echinacea are limited to its use in prevention or treatment of the common cold (e.g. David 2019, Karsch-Volk 2014). No systematic reviews or controlled clinical trials have focused on its use in cancer patients. Except for one small study with historical controls, only small uncontrolled studies are available and most use combination products, which do not allow any conclusions about echinacea’s efficacy.

Supportive care
• Prevention of treatment-related adverse effects: no convincing evidence exists

Antitumour treatment
• No convincing evidence exists of an effect on survival time.

Description of studies

Supportive care

Treatment-related adverse effects

Several early trials published in German (e.g. Sartor 1972) reported potentially relevant effects on radiation–induced leukopenia but the product used was a combination of herbs (Esberitox®) and so the contribution of Echinacea cannot be determined. A subsequent study with the same product found no detectable effect on 12 cancer patients’ lymphocyte counts (Elsasser-Beile 1996).

One small open prospective study with matched historical controls tested whether a polysaccharide fraction isolated from Echinacea purpurea reduced unwanted effects of chemotherapy (Melchart 2002). 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.

Antitumour treatment

Only a few attempts to investigate echinacea’s role as an anti-cancer agent have been made. Preliminary, small, uncontrolled studies have investigated the anti-cancer effects of Echinacea purpurea extracts combined with chemotherapy and thymostimulin; one such study in patients with advanced metastatic colorectal cancer who had received surgery and/or chemotherapy (Lersch 1992a).  Similar studies were conducted by the same research group in small numbers of patients with advanced pancreatic, hepatocellular and gastrointestinal cancers (Lersch 1990a, Lersch 1990b, Lersch 1992b). All studies involved combination treatment, very small numbers of patients and no control group and have not been replicated so no conclusions can be drawn.

Is it safe?

Adverse events

Safety data mainly derived from clinical trials and single case reports indicated that echinacea is generally well-tolerated (Huntley 2005). Most frequently reported adverse effects include gastro-intestinal upsets and rashes (Jeschke 2009, Engdal 2008). Individuals with atopia or sensitivity to the Asteraceae/Compositae plant family might be at increased risk of allergic reactions (urticaria, bronchospasm and anaphylaxis) (Jeschke 2009). Administration of echinacea by injection has been associated with shivering, fever and muscle weakness (Engdal 2008). Echinacea has been implicated as a possible causative agent in joint and muscle pain, liver-related problems such as raised liver enzymes and hepatitis, haematological problems such as leucopenia and Sjögren’s syndrome but these have been reported only rarely (NMD 2021, Engdal 2008). It has been suggested that Echinacea may interfere with the immune and inflammatory response against COVID-19 but no strong evidence exists on Echinacea either as beneficial or detrimental in Covid-19 (NMD 2021).

Short-term treatment with echinacea has been assessed as likely to be safe (NMD 2021). Different forms of echinacea have been used apparently safely in trials for different lengths of time, lasting anywhere between 10 days and 6 months (NMD 2021). The EMA 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 respectively for Echinacea purpurea (EMA 2015). Duration of treatment for other indications is unclear and there is insufficient reliable evidence about the safety of long-term treatment with echinacea (NMD 2021).

Contraindications/Warnings

Echinacea may cause a rash in children which may be due to an allergic reaction and which could be severe in some children. The EMA does not recommend the use in children under 12 years of age, while use is advised against by the UK Medicines and Healthcare Regulatory Agency 2012. The EMA  states that use below 1 year of age is contraindicated (EMA 2015).

Limited data (several hundreds of exposed pregnancies) did not indicate adverse effects of Echinacea purpurea on pregnancy or on the health of the foetus/newborn child (EMA 2015). No data exist on the safety and efficacy of echinacea in nursing mothers or infants (Drugs and Lactation database 2021). Due to the lack of data, the EMA recommends that echinacea should be avoided in pregnancy and while breast feeding (EMA 2015). The EMA 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 system (EMA 2015).

Products available as echinacea vary in composition depending on the species, parts of the plant used and the extraction method used in production (Karsch-Volk 2014). While products tend to be standardised, the constituent(s) on which this is based varies (NMD 2021). Analysis of a range of echinacea products has revealed that many were mislabelled, contained substances other than the herb or actually contained no echinacea (Chardonnet 2006, Gilroy 2003). Quality of echinacea products depends, at least partially, on the regulatory standards and good manufacturing requirements in the country in which the product is manufactured.

Interactions

Echinacea appears to inhibit Cytochrome P450 1A2 enzymes in humans and so, in theory, might increase levels of drugs metabolised by CYP1A (NMD 2021). These include paracetamol, amitriptyline, diazepam, oestradiol, ondansetron, propranolol, theophylline, warfarin and others.

Preliminary evidence suggests that echinacea also affects cytochrome P4450 3A4. The effects are complex as it inhibits intestinal CYP3A4 and induces hepatic CYP3A4 enzymes (NMD 2021). 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 thrombocytopenia requiring a platelet transfusion (Bossaer 2012).

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. purpurea (Goey 2013).

As echinacea has immuno-stimulating activity, in theory, it may interfere with immunosuppressant treatment (NMD 2021).

References

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