Echinacea

Echinacea/Drug Interactions:

  • In general, the interactions of prescription drugs with herbal supplements such as echinacea have been reviewed (158), and the effects of echinacea when administered with other agents have been summarized (159; 160). According to human research, pharmacokinetic and drug interactions with echinacea may be minimal (161; 162).
  • AnestheticsAnesthetics: Theoretically, potential interactions may occur between echinacea and anesthetics (87). However, clear evidence supporting this hypothesis is lacking.
  • AntibioticsAntibiotics: In vitro, Echinaforce?, a commercially available standardized extract of Echinacea purpurea, reversed proinflammatory responses of bronchial epithelial cells to Streptococcus pyogenes, Hemophilus influenzae, Legionella pneumophilia, Staphylococcus aureus (both methicillin-sensitive and -resistant strains), and Mycobacterium smegmatis; antibactericidal activity of Echinaforce? against Streptococcus pyogenes, Hemophilus influenzae, and Legionella pneumophilia was observed as well (163). In cell culture research, a dose-dependent antiadhesion effect of Echinacea purpurea was observed against Campylobacter jejuni, a common bacterial cause of diarrhea; significantly lower antiadhesion activity against C. jejuni was observed for Echinacea angustifolia species as well (164). In cell research, Echinaforce?, a commercially available preparation of Echinacea purpurea, induced bactericidal activity against laboratory strains and clinical isolates of Propionibacterium acnes, a common cause of acne (165). In a similar study, four echinacea preparations that contained different chemical components were shown to inhibit the growth of Leishmania donovani, Leishmania major, and Trypanosoma brucei bacteria strains (166). According to animal research, echinacea may have antibiotic effects, as it has been shown to reduce the microbicidal activity of Candida albicans and Listeria monocytogenes in mice immunosuppressed with cyclophosphamide or cyclosporin A (167). However, in human research, echinacea lacked antibacterial effects against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans (168). Clinical trials have shown that Esberitox? (Schaper & Br?mmer, Salzgitter, Germany), an herbal combination therapy that contains Thujae occidentalis herba (white cedar), Baptisiae tinctoriae radix (wild indigo), Echinaceae purpureae radix (purple coneflower), and Echinaceae pallidae radix (pale purple coneflower), may have antibacterial effects (169; 170; 171; 172). According to a review, the combination of components that may be isolated from echinacea through extraction may have antiviral, antimicrobial, and immune-modulatory activity when administered at noncytotoxic concentrations (23). There is one poorly described case report of a 19 year-old patient who ingested amoxicillin and an unclear echinacea preparation and then died after developing rhabdomyolysis and going into shock. Further details were not provided (66).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, echinacea has been shown to increase (S)-warfarin clearance, but a statistically significant effect on platelet aggregation was lacking (57).
  • Anti-inflammatoriesAnti-inflammatories: Based on cell culture research, the alkamides of Echinacea purpurea, Echinacea pallida, and Echinacea angustifolia are believed to induce anti-inflammatory effects (173). The herbal combination Esberitox? has been evaluated in clinical studies as a treatment option for inflammatory conditions (174; 144; 175), but human evidence of the anti-inflammatory effects of echinacea alone are limited.
  • AntineoplasticsAntineoplastics: Echinacea may have additive effects when taken in combination with antineoplastics, because constituents of the root oil of Echinacea angustifolia and Echinacea pallida have been shown to possess antitumor activity in vivo (176). According to animal research, a hydrophilic polysaccharide complex isolated from echinacea increased the antitumor and antimetastatic activity of cyclophosphamide (177). Preliminary clinical studies have been conducted to assess the safety of combination chemotherapy including Echinacin? (Echinacea purpurea) (134; 118). In a case report of a 61 year-old man undergoing chemoradiation with cisplatin and etoposide and also taking echinacea, the patient experienced thrombocytopenia requiring platelet transfusion, due to possible CYP3A4 inhibition by echinacea (88). Once echinacea was discontinued, the patient no longer required platelet transfusions; therefore, it is suggested that echinacea be avoided in patients receiving etoposide and other CYP 3A4 substrate chemotherapeutic agents.
  • AntiretroviralsAntiretrovirals: According to a review, for HIV patients undergoing highly active antiretroviral therapy (HAART), the use of alternative medicinal therapies, including echinacea, may interact with and influence the effectiveness of HAART (49). In human research, coadministration of echinacea and darunavir-ritonavir to individuals with HIV reduced the concentrations of darunavir in the blood, although an effect from echinacea on the pharmacokinetics of darunavir and ritonavir was lacking in this study (178). In another human trial, Echinacea purpurea and etravirine were taken together in HIV-infected patients and the author concluded that this combination is safe to take together and lacks any serious effects (179).
  • AntispasmodicsAntispasmodics: According to secondary sources, echinacea may have antispasmodic effects.
  • Antiviral agentsAntiviral agents: Echinacea may possess antiviral activity against influenza virus (180), vesicular stomach virus, and herpes simplex virus (HSV-1 and HSV-2) (181). The relevance of these in vivo findings remains unclear. Echinacea has been suggested as modulating hepatic enzyme activity, including the CYP450 3A4 enzyme (182). Thus, concurrent echinacea use with other agents that alter CYP450 activity, such as the flu vaccine, may alter the effects of certain agents metabolized by CYP450 3A4. In addition, cell culture research has shown that a commercially available echinacea product inhibits the metabolic activation of oseltamivir (183). Finally, clinical trials have suggested that Esberitox? may have antiviral effects (184; 143; 171; 85; 185; 145). According to a review, the combination of components that may be isolated from echinacea through extraction may have antiviral, antimicrobial, and immune-modulatory activity when administered at noncytotoxic concentrations (23).
  • Anxiolytic agentsAnxiolytic agents: In a study involving rats and humans, Echinacea angustifolia extract had anxiolytic effects; therefore, theoretical additive effects may occur (92). The mechanism is unclear.
  • CaffeineCaffeine: In clinical research, echinacea reduced the oral clearance of caffeine, which the investigators attributed to the inhibition of cytochrome P450 1A2 by echinacea (182; 186).
  • Cardiac glycosidesCardiac glycosides: In cell culture research, Echinacea purpurea reduced the flux of drugs such as digoxin by inhibiting p-glycoprotein transporter activity (187).
  • CorticosteroidsCorticosteroids: In theory, echinacea's immunostimulant properties may interfere with immunosuppressant therapy (including prednisone) (61). This possibility has not been systematically studied in humans.
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: According to a literature review, echinacea may interact with cytochrome P450 (CYP)-metabolizing enzymes, but the clinical potential of this interaction may be minor (51). However, further research into the interaction potential is merited (67; 188; 189). In laboratory research and systematic reviews, echinacea has both mildly inhibited (190; 162) and induced CYP3A4 activity (68; 162); however, according to other reviews, the effect of echinacea on CYP3A4 is unclear (186). In human research, echinacea reduced the oral clearance of substrates of CYP1A2, but an effect on the oral clearance of the substrates of CYP2D6 or CYP2C9 was lacking (182); however, a systematic review suggested there is mild inhibition of CYP1A2 and CYP2C9 (162). Echinacea selectively modulated the catalytic activity of CYP3A at hepatic and intestinal sites (182). Biochemical alkylamides found in echinacea that contain terminal alkyne groups may inhibit CYP-regulated metabolism of other substances (191). However, according to a review, a clinically significant effect from echinacea on the activity of CYP enzymes is lacking (192). According to a review of in vivo research, Echinacea purpurea lacked a clear effect on most of the CYPs examined; however, mild inhibition may be possible (193).
  • Dental agentsDental agents: In human research, an Echinacea purpurea-containing mouthwash decreased the gingival index (GI) score; therefore, theoretical additive effects may occur (148).
  • Disulfiram (Antabuse?)Disulfiram (Antabuse?): Echinacea tinctures often contain high alcohol content (15-90%) and theoretically may elicit a disulfiram reaction; however, evidence is lacking. Echinaforce? (A. Vogel Bioforce AG, Switzerland) is extracted with 57.3% alcohol; therefore, a disulfiram reaction may occur (86).
  • Econazole nitrate (Spectazole?)Econazole nitrate (Spectazole?): There is preliminary clinical evidence to suggest that the use of echinacea with topical econazole may decrease the recurrence rate of vaginal Candida infections (194).
  • HepatotoxinsHepatotoxins: Numerous reports of hepatitis have been associated with echinacea use (54). However, specific details of these cases are lacking, and there is unclear evidence from basic science or human reports that echinacea causes significant liver toxicity. Some researchers have noted that echinacea lacks the 1,2-unsaturated necrine ring system that causes hepatotoxicity of pyrrolizidine alkaloids (65). According to a case report, a 45 year-old male presented to the hospital with acute cholestatic autoimmune hepatitis (ACAH), which was attributed to echinacea use (150).
  • ImmunosuppressantsImmunosuppressants: According to literature review, echinacea may decrease the effects of immunosuppressants due to its immunostimulant activity (195; 61). In theory, echinacea may interfere with immunosuppressants, including azathioprine, cyclosporine, and prednisone. This possibility has not been systematically studied in humans. According to preliminary in vitro and in vivo studies, as well as human clinical trials, echinacea-containing combination products (Esberitox?) may have immunostimulant or immunomodulating effects (137; 196; 197; 198; 171; 199; 200; 201; 202; 203; 204; 205; 138; 206; 207; 140; 141; 208; 209; 210).
  • Metronidazole (Flagyl?)Metronidazole (Flagyl?): A disulfiram reaction may occur when metronidazole and alcohol are used concomitantly. Due to the high alcohol content in some echinacea tinctures, this combination theoretically may cause such a reaction. Echinaforce? (A. Vogel Bioforce AG, Switzerland) is extracted with 57.3% alcohol; therefore, a disulfiram reaction may occur (86).
  • P-glycoprotein regulated agentsP-glycoprotein regulated agents: In cell culture research, Echinacea purpurea reduced the flux of drugs such as digoxin by inhibiting p-glycoprotein transporter activity; an effect from echinacea on other substrates of the p-glycoprotein transporter cannot be excluded (187).
  • Photosensitizing agentsPhotosensitizing agents: In tissue research, UVA and UVB light caused a reduction in nerve ending densities, but treatment with a skin care emulsion that contained Echinacea purpurea extract prevented UV-induced damage (211).
  • Renally eliminated agentsRenally eliminated agents: According to a review, echinacea has the potential to interact with drugs that are cleared from the body by the kidney (212); further details are lacking.
  • SteroidsSteroids: In theory, echinacea's immunostimulant properties may interfere with immunosuppressant therapy (including prednisone) (61). This possibility has not been systematically studied in humans.

    • Echinacea/Herb/Supplement Interactions:

  • In general, the effects of echinacea when administered with other agents have been summarized (159; 160). According to human research, pharmacokinetic and drug interactions with echinacea may be minimal (161; 162).
  • AnestheticsAnesthetics: Theoretically, potential interactions may occur between echinacea and anesthetics. However, clear evidence supporting this hypothesis is lacking (87).
  • AntibacterialsAntibacterials: In in vitro research, Echinaforce?, a commercially available standardized extract of Echinacea purpurea, has been shown to reverse proinflammatory responses of bronchial epithelial cells to Streptococcus pyogenes, Hemophilus influenzae, Legionella pneumophilia, Staphylococcus aureus (both methicillin-sensitive and resistant strains), and Mycobacterium smegmatis; the antibactericidal activity of Echinaforce? against Streptococcus pyogenes, Hemophilus influenzae, and Legionella pneumophilia was observed as well (163). In cell culture research, a dose-dependent antiadhesion effect of Echinacea purpurea was observed against Campylobacter jejuni, a common bacterial cause of diarrhea; significantly lower antiadhesion activity against C. jejuni was observed for Echinacea angustifolia species as well (164). In cell research, Echinaforce?, a commercially available preparation of Echinacea purpurea, induced bactericidal activity against laboratory strains and clinical isolates of Propionibacterium acnes, a common cause of acne (165). In a similar study, four echinacea preparations that contained different chemical components were shown to inhibit the growth of Leishmania donovani, Leishmania major, and Trypanosoma brucei bacteria strains (166). According to animal research, echinacea may have antibiotic effects, as it has been shown to reduce the microbicidal activity of Candida albicans and Listeria monocytogenes in mice immunosuppressed with cyclophosphamide or cyclosporin A (167). However, in human research, echinacea lacked antibacterial effects against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans (168). Clinical trials have shown that Esberitox? (Schaper & Br?mmer, Salzgitter, Germany), an herbal combination therapy that contains Thujae occidentalis herba (white cedar), Baptisiae tinctoriae radix (wild indigo), Echinaceae purpureae radix (purple coneflower), and Echinaceae pallidae radix (pale purple coneflower), may have antibacterial effects (169; 170; 171; 172). According to a review, the combination of components that may be isolated from echinacea through extraction may have antiviral, antimicrobial, and immune-modulatory activity when administered at noncytotoxic concentrations (23).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, echinacea has been shown to increase the clearance of (S)-warfarin, but a statistically significant effect on platelet aggregation was lacking (57).
  • Anti-inflammatoriesAnti-inflammatories: Based on cell culture research, the alkamides of Echinacea purpurea, Echinacea pallida, and Echinacea angustifolia are believed to induce anti-inflammatory effects (173). The herbal combination Esberitox? has been evaluated in clinical studies as a treatment option for inflammatory conditions (174; 144; 175), but human evidence of the anti-inflammatory effects of echinacea alone are limited.
  • AntineoplasticsAntineoplastics: Echinacea may have additive effects when taken in combination with antineoplastics, because constituents of the root oil of Echinacea angustifolia and Echinacea pallida have been shown to possess antitumor activity in vivo (176). According to animal research, a hydrophilic polysaccharide complex isolated from echinacea increased the antitumor and antimetastatic activity of cyclophosphamide (177). Preliminary clinical studies have been conducted to assess the safety of combination chemotherapy including Echinacin? (Echinacea purpurea) (134; 118). In a case report of a 61 year-old man undergoing chemoradiation with cisplatin and etoposide and also taking echinacea, the patient experienced thrombocytopenia requiring platelet transfusion ,due to possible CYP3A4 inhibition by echinacea (88). Once echinacea was discontinued, the patient no longer required platelet transfusions; therefore, it is suggested that echinacea be avoided in patients receiving etoposide and other CYP 3A4 substrate chemotherapeutic agents.
  • AntioxidantsAntioxidants: Echinacea belongs to a class of antioxidants (6; 7; 8; 9; 10; 11), and theoretically additive effects may occur when taken with other herbs or supplements with antioxidant effects.
  • AntispasmodicsAntispasmodics: According to secondary sources, echinacea may have antispasmodic effects.
  • AntiviralsAntivirals: Echinacea may possess antiviral activity against influenza virus (180), vesicular stomach virus, and herpes simplex virus (HSV-1 and HSV-2) (181). The relevance of these in vivo findings remains unclear. Echinacea has been suggested as modulating hepatic enzyme activity, including the CYP450 3A4 enzyme (182). Thus, concurrent echinacea use with other agents that alter CYP450 activity, such as the flu vaccine, may alter the effects of certain agents metabolized by CYP450 3A4. In addition, cell culture research has shown that a commercially available echinacea product inhibited the metabolic activation of oseltamivir (183). Finally, clinical trials suggested that Esberitox? may have antiviral effects (184; 143; 171; 85; 185; 145). According to a review, the combination of components that may be isolated from echinacea through extraction may have antiviral, antimicrobial, and immune-modulatory activity when administered at noncytotoxic concentrations (23).
  • AnxiolyticsAnxiolytics: In a study involving rats and humans, Echinacea angustifolia extract had anxiolytic effects; therefore, theoretical additive effects may occur (92). The mechanism is unclear.
  • AstragalusAstragalus: Echinacea, astragalus, and glycyrrhiza herbal tinctures stimulated immune cells, as quantified by CD69 expression on CD4 and CD8 T cells (99). This activation took place within 24 hours of ingestion and continued for at least seven days. In addition, these three herbs had an additive effect on CD69 expression when used in combination.
  • Caffeine-containing agentsCaffeine-containing agents: In clinical research, echinacea reduced the oral clearance of caffeine, which the investigators attributed to the inhibition of cytochrome P450 1A2 by echinacea (182; 186).
  • Cardiac glycosidesCardiac glycosides: In cell culture research, Echinacea purpurea reduced the flux of drugs such as digoxin by inhibiting p-glycoprotein transporter activity (187).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: According to literature review, echinacea may interact with cytochrome P450 (CYP)-metabolizing enzymes, but the clinical potential of this interaction may be minor (51). However, further research into the interaction potential is merited (67; 188; 189). In laboratory research and systematic reviews, echinacea has both mildly inhibited (190; 162) and induced CYP3A4 activity (68; 162); however, based on other reviews the effect of echinacea on CYP3A4 is unclear (186). In human research, echinacea reduced the oral clearance of substrates of CYP1A2, but an effect on the oral clearance of the substrates of CYP2D6 or CYP2C9 was lacking (182); however, a systematic review suggested there is mild inhibition of CYP1A2 and CYP2C9 (162). Echinacea selectively modulated the catalytic activity of CYP3A at hepatic and intestinal sites (182). Biochemical alkylamides found in echinacea that contain terminal alkyne groups may inhibit CYP-regulated metabolism of other substances (191). However, according to a review, a clinically significant effect of echinacea on the activity of CYP enzymes is lacking (192). According to a review of in vivo research, Echinacea purpurea lacked a clear effect on most of the CYPs examined; however, mild inhibition may be possible (193).
  • Dental agentsDental agents: In human research, an Echinacea purpurea-containing mouthwash decreased the gingival index (GI) scores; therefore, theoretical additive effects may occur (148).
  • GlycyrrhizaGlycyrrhiza: Echinacea, astragalus, and glycyrrhiza herbal tinctures stimulated immune cells, as quantified by CD69 expression on CD4 and CD8 T cells (99). This activation took place within 24 hours of ingestion and continued for at least seven days. In addition, these three herbs had an additive effect on CD69 expression when used in combination.
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: Numerous reports of hepatitis have been associated with echinacea use (54). However, specific details of these cases are lacking, and there is unclear evidence from basic science or human reports that echinacea causes significant liver toxicity. Some researchers have noted that echinacea lacks the 1,2-unsaturated necrine ring system that causes hepatotoxicity of pyrrolizidine alkaloids (65). According to a case report, a 45 year-old male presented to the hospital with acute cholestatic autoimmune hepatitis (ACAH), which was attributed to echinacea use (150).
  • ImmunostimulantsImmunostimulants: Echinacea has been studied alone and in combination preparations for immune system stimulation (including in patients receiving cancer chemotherapy), but it remains unclear if there are clinically significant benefits (69; 70; 71; 72; 73).
  • ImmunosuppressantsImmunosuppressants: According to a review, echinacea may decrease the effects of immunosuppressants due to its immunostimulant activity (195; 61). In theory, echinacea may interfere with immunosuppressants, including azathioprine, cyclosporine, and prednisone. This possibility has not been systematically studied in humans. According to preliminary in vitro and in vivo studies, as well as human clinical trials, echinacea-containing combination products (Esberitox?) may have immunostimulative or immunomodulating effects (137; 196; 197; 198; 171; 199; 200; 201; 202; 203; 204; 205; 138; 206; 207; 140; 141; 208; 209; 210).
  • KavaKava: Multiple reports of hepatotoxicity associated with kava use have been reported, believed to be most common with heavy or chronic use, according to secondary sources. Caution should be exercised with concomitant use of echinacea, which some natural medicine practitioners have warned may cause liver toxicity as well. However, there is no clear evidence from basic science or human reports that echinacea causes significant liver toxicity. Some have noted that it lacks the 1,2-unsaturated necrine ring system that causes hepatotoxicity of pyrrolizidine alkaloids (65). This potential interaction remains theoretical.
  • P-glycoprotein regulated agentsP-glycoprotein regulated agents: In cell culture research, Echinacea purpurea reduced the flux of drugs such as digoxin by inhibiting p-glycoprotein transporter activity; an effect of echinacea on other substrates of the p-glycoprotein transporter cannot be excluded (187).
  • PhotosensitizersPhotosensitizers: In tissue research, UVA and UVB light caused a reduction in nerve ending densities, but treatment with a skin care emulsion that contained Echinacea purpurea extract prevented UV-induced damage (211).
  • Renally eliminated agentsRenally eliminated agents: According to one review, echinacea has the potential to interact with drugs that are cleared from the body by the kidney (212); further details are lacking.
  • VitaminsVitamins: While echinacea itself has not been found to interact with vitamin B, many echinacea preparations are coupled with goldenseal (Hydrastis canadensis), which is purportedly an antibiotic and may decrease intestinal microflora and absorption of vitamin B (213). These preparations may have low levels of echinacea and may not be efficacious against virus-induced upper respiratory tract infections.

    • Echinacea/Food Interactions:

  • Insufficient available evidence.

    • Echinacea/Lab Interactions:

  • CytokinesCytokines: According to a review of the literature, Echinacea spp. may influence the activity of multiple cytokines (214; 35). Nonspecific effects included increases in macrophage proliferation and phagocytosis, as well as secretion of interferon, tumor necrosis factor, and interleukin-1 (in vitro and in vivo) (215; 216; 217; 218; 219; 220; 221; 222; 6; 223). In clinical research, treatment with species of echinacea including Echinacea purpurea and Echinacea tennesseensis, has been shown to increase T cell (CD3+, CD4+, CD8+) and natural killer cell activation (99; 90; 107), cytokine (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma) production (224; 107; 225), and chemokine (MCP-1) levels (225). Also, decreased sIL-2R release has been observed in some research (107), and levels of IL-1beta, IL-6, IL-8, IL-12, and TNF-alpha have been shown to be reduced in some individuals after echinacea treatment (225; 226). In other clinical research, individuals administered echinacea showed increased levels of EPO and IL-3, although statistically significant changes in red blood cell count, hematocrit, or hemoglobin were lacking (97). In animal research, echinacea increased the production of IL-2, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1, and tumor necrosis factor-alpha (TNF-alpha) (203). In a separate animal study, echinacea increased the production of IL-6 (199). A specific alkamide, dodeca-2E,4E,8Z,10Z(E)-tetraenoic acid isobutylamide, which was isolated from Echinacea purpurea roots, was shown to inhibit the expression and activity of cyclooxygenase (COX)-2, as well as the expression of inducible nitric oxide synthase (iNOS), TNF-alpha, IL-1alpha, IL-6, monocyte chemotactic protein (MCP)-1, and macrophage inflammatory protein (MIP)-1beta in macrophages; however, heme oxygenase-1 protein expression increased in macrophages after echinacea treatment (173). According to cell culture research, N-alkylamides isolated from ethanol extracts of Echinacea purpurea radix and herba may activate cannabinoid receptor type-2 and promote calcium release, may stimulate IL-10 expression, and may inhibit TNF-alpha expression, leading to anti-inflammatory and immunomodulatory effects (227). According to cell culture research using skin fibroblasts and human bronchial epithelial cells, Echinaforce? has been shown to reduce the secretion of IL-6 and IL-8 caused by exposure to Propionibacterium acnes (165) and Leishmania donovani (166), as well as the secretion of these proteins by human bronchial epithelial cells when exposed to rhinoviruses (228). In addition, Echinaforce? has been shown in laboratory studies to reduce the secretion of IL-6 and IL-8 by human airway epithelium tissue models (EpiAirwayTM tissue) after the tissue had been exposed to rhinovirus type 1A (229). According to cell culture research, the American federally endangered species of echinacea, Echinacea laevigata, may affect IL-10 and mononuclear cell growth similarly to Echinacea pallida; however, significant effects on TNF-alpha and IL-2 were lacking for this species (230). In other cell culture research, tinctures made with only the roots of Echinacea tennesseensis increased the production of IL-1beta, IL-10, and TNF-alpha (231). In vitro, Echinacea pallida and Echinacea purpurea increased the production of immunoglobulin M (IgM) from mouse lymphocytes (NMRI) and the production of IL-6 and nitrite from alveolar mouse macrophages (MH-S cells) (199). At low concentrations, undeca-2-ene-8,10-diynoic acid isolated from Echinacea angustifolia has been shown to inhibit the secretion of IL-2 in T lymphocyte (Jurkat) cells, but the addition of a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) reversed this effect (232).
  • Immunoglobulins (IgA)Immunoglobulins (IgA): Echinacea purpurea was found to significantly reduce s-IgA and the secretion rate of s-IgA at the beginning of a mucosal immunity test in humans (233). Echinacea did not significantly decrease s-IgA or the secretion rate of s-IgA after intervention.
  • Immunoglobulins (IgG)Immunoglobulins (IgG): Echinacea angustifolia (Poliacea?) increased immunoglobulin G (IgG) in humans (109).
  • Immunoglobulins (IgM)Immunoglobulins (IgM): In vitro, Echinacea pallida and Echinacea purpurea increased the production of immunoglobulin M (IgM) from mouse lymphocytes (NMRI) and the production of IL-6 and nitrite from alveolar mouse macrophages (MH-S cells) (199).
  • Liver function testsLiver function tests: Echinacea has been associated with elevated liver enzymes and hepatitis (74; 54). Patients consuming large amounts of echinacea have experienced elevations in transaminase that resolved with discontinuation of the herb (74).
  • Platelet countPlatelet count: In clinical research evaluating the effect of echinacea on chemoradiation-induced side effects, Esberitox? had a favorable effect on hematological parameters, particularly for hemoglobin and hematocrit and less frequently for leukocytes, granulocytes, monocytes, lymphocytes, and thrombocytes (141). In a case report of a 61 year-old man undergoing chemoradiation with etoposide and cisplatin and taking Echinacea supplementation, it is suggested that use of echinacea may be associated with profound thrombocytopenia (platelet count reaching a nadir of 16 ? 10(3)/L) (88).
  • Serum erythropoietin levelsSerum erythropoietin levels: In clinical research, participants who were administered echinacea had a statistically significant increase in erythropoietin (EPO) levels compared to baseline (12.37 ? 0.87mU/mL) after day 7 (15.75 ? 0.64mU/mL; p=0.007), 14 (18.88 ? 0.71mU/mL; p<0.001), and 21 (16.06 ? 0.55mU/mL; p<0.003). This change was statistically significant when compared to participants receiving placebo (p<0.001 at days 7 and 14; p=0.002 at day 21) (94). In other clinical research, individuals who were administered echinacea showed increased levels of EPO and IL-3, although statistically significant changes in red blood cell count, hematocrit, or hemoglobin were lacking (97). In healthy males taking echinacea, serum erythropoietin levels were significantly increased on days seven (10.02 ? 0.72mU/mL vs. 17.79 ? 1.52mU/mL, p<0.001), 14 (10.46 ? 0.91mU/mL vs. 20.21 ? 0.43mU/mL, p<0.001), and 21 (8.64 ? 0.81mU/mL vs. 16.84 ? 2.17mU/mL, p=0.002) (95).
  • Serum lymphocyte levelsSerum lymphocyte levels: Clinical research has shown that Esberitox? N affects hematological parameters, most frequently hemoglobin and hematocrit levels and less frequently leukocyte, granulocyte, monocyte, lymphocyte, and thrombocyte levels (141), although these results have been refuted in other studies (234). Athletes given Esberitox? while still training and competing have shown an increase in lymphocyte and leukocyte cell counts (207). In human research, echinacea use resulted in a longer duration of increased monocyte and neutrophil counts, as well as decreased CD4+ and increased CD16+ (90). In clinical research, Echinacea purpurea increased CD4, CD8, T-cell, and NK-cell counts (99). In other clinical research, treatment with Echinilin? caused a decrease in CD4+ cell counts after three days of treatment; however, an effect on CD3+, CD8+, or CD20+ was lacking (90). In clinical research evaluating the effect of echinacea on chemoradiation-induced side effects, Esberitox? had a favorable effect on hematological parameters, particularly for hemoglobin and hematocrit and less frequently for leukocytes, granulocytes, monocytes, lymphocytes, and thrombocytes (141). Echinacea may affect subpopulations, specifically, the number of CD8+ T lymphocytes and natural killer cells (235). In other animal research, echinacea lacked influence on mouse lymphocyte proliferation (199). In animal studies using mice, Esberitox? has been shown to activate macrophages and leukocytes (236; 237; 238).
  • White blood cell countWhite blood cell count: In clinical research, individuals administered two 275mg Echinacea? (Strong Nature, Serbia) tablets twice daily for two weeks after exposure to radiation showed a statistically significant change in the percentage of monocytes (Z=2.09, p<0.04) (91). Echinacea may invoke an immune response through altered expression of hsp70 and increased white cell count (6). In clinical research evaluating the effect of echinacea on chemoradiation-induced side effects, Esberitox? had a favorable effect on hematological parameters, particularly for hemoglobin and hematocrit and less frequently for leukocytes, granulocytes, monocytes, lymphocytes, and thrombocytes (141). However, in other clinical trials, the influence of combination echinacea treatments (Esberitox?) on leukocyte counts was unclear (234; 209; 208). In animal studies, treatment with echinacea induced specific immune responses, including the activation of alternate complement pathway components and elevated levels and activity of T lymphocytes and natural killer (NK) cells (239; 240; 241; 111; 242). In cell culture research, 50% ethanol tinctures of Echinacea tennesseensis roots, leaves, and flowers increased the proliferation of peripheral blood mononuclear cells (231).