All Essential Benefits/Effects/Facts & Information

Echinacea is a herbal supplement that is commonly used either at the first signs of sickness (in an attempt to accelerate the rate of recovery) or daily as a preventative supplement in persons who are sick frequently (in hopes of reducing the frequency of which they get sick). The term 'echinacea' refers to a genera of plants, and a few species in this family including purpurea and augustifolia are desired due to their alkylamide content (seen as the active ingredients).

Overall, echinacea appears to be somewhat effective for fighting off sickness and accelerating the rate of recovery in sickness but both of these claims are highly variable. There are trials suggesting remarkable recovery rates, and there are trials suggesting no benefits whatsoever. When looking at meta-analyses on the topic, there appears to be a positive and protective effect of echinacea on sickness frequency (in those who are frequently sick) and in accelerating the rate of recovery; the effect size, however, is not large. When looking at the severity of sickness or symptoms of the cold, echinacea does not appear to have any significant influence (unlike something like Andrographis paniculata).

The mechanisms are thought to either be due to macrophage stimulation (which although the alkylamides can stimulate macrophages via cannabinoid receptors, contamination of supplements with lipopolysaccharide/LPS appears to be the main stimulatory) or from producing more antigen-specific immunoglobulins.

This variability is likely due to the alkylamide mixture, where the term 'alkylamide' refers to over 20 similarly structured compounds that vary in their ratios to one another from one batch of echinacea to the next (due to growing conditions, usually), although some context-dependent effects of echinacea cannot be ruled out.

Overally, echinacea may be the best option available at this time but by no means is a highly reliable intervention for reducing cold frequency or sickness length.

Confused about supplements?

Free 5 day supplement course

Things To Know

Also Known As

Brauneria purpurea, Echinacea intermedia, Rudbeckia purpurea, Purple coneflower herb, Coneflower, red sunflower

Things to Note

  • After processing, echinacea bioactives may be sensitive to light and heat. It may be prudent to store echinacea in a cool (5°C or lower) and dark place

Is a Form Of

Caution Notice

It is possible to be allergic to echinacea as a plant, and this may be related to ragweed allergies. Medical Disclaimer

How to Take

Recommended dosage, active amounts, other details

For dehydrated powders (including encapsulated echinacea) the species of purpuera tends to be used and oral doses are taken upwards of 300mg thrice a day (900mg daily) and 500mg thrice daily (1,500mg daily).

Tinctures of an ethanolic extract of the aerial parts (leaves and stems) appears to be used in the concentration of 2.5mL thrice a day or up to 10mL daily.

There is no much evidence as to whether these are the optimal doses, and studies seem to be very hetereogeneous in their benefits due to lack of standardization.

Confused about supplements?

Free 5 day supplement course

Editors' Thoughts on Echinacea

The variability seen with echinacea supplements likely leads back to one of the following:

  • Immunostimulation secondary to acting on cannabinoid receptors, with the alkylamides being numerous in their quantity and effects (some agonistic, some antagonistic) which make it hard to predict overall cannabinoid signalling

  • LPS contamination of echinacea actually contributing to the observed effects of immunostimulation

So although it is not wholly clear why echinacea is so variable in its effects, we at least know a few reasons why it might be and know that it is indeed variable.

Hard to come up with an alternative for echinacea to be honest, Andrographis paniculata is more reliable but is based on much less evidence (and the first few studies usually seem to be more promising than the battery of ones to follow, which tends to be seen with many supplements including echinacea). Echinacea may be currently the best option for acute treatment of a cold or flu, but this is partially based on how there aren't too many options.

Kurtis Frank

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects echinacea has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Length of Sickness Notable Very High See all 6 studies
Although a high variability exists, the meta-analysis has concluded a 1.4-day reduction in sickness when it occurs relative to placebo. As echinacea is also a comparator for sickness, this reduction in notable
Upper Respiratory Tract Infection Risk Notable High See all 11 studies
The reduction in rate of sickness seen with echinacea as a daily supplement is highly effective in some instances, but subject to a high degree of variability. It is notable due to it being a comparator.
Symptoms of the Common Cold - Very High See all 4 studies
Insufficient evidence to support modification of symptoms of sickness
Erythropoietin Minor Very High See study
Lone trial noted an increase in EPO production without an accompanying increase in red blood cell count; practical significance of these results uncertain
Exercise-Induced Immune Suppression Minor Very High See study
Possible effects, but study assessed salivary IgA (biomarker of immunity) and not sickness rates; hard to assess potency.
Oxygenation Cost of Exercise Minor Very High See study
Effective, but to a small degree based on one trial.
VO2 Max Minor Very High See study
Not an astounding increase in VO2 max, requires replication.
Blood Pressure - Very High See study
No significant known effects on blood pressure
Red Blood Cell Count - Very High See study
Oddly ineffective despite an increase in erythropoetin seen
Sleep Quality - Very High See study
Likely related to the inefficacy in treating symptoms, but no significant ability to aid in sleep quality during or without sickness

Studies Excluded from Consideration

  • Excluded due to being confounded with the inclusion of other nutrients[1][2][3]

  • Duplicated[4]

Disagree? Join the Echinacea Discussion

Scientific Research

Table of Contents:

  1. 1 Sources and Composition
    1. 1.1 Sources
    2. 1.2 Composition
    3. 1.3 Stability and Properties
    4. 1.4 Brand Name Products
  2. 2 Pharmacology
    1. 2.1 Absorption
    2. 2.2 Serum
    3. 2.3 Enzymatic Interactions
  3. 3 Neurology
    1. 3.1 Cannabinoid
    2. 3.2 Anxiety
  4. 4 Cardiovascular Health
    1. 4.1 Blood Pressure
  5. 5 Inflammation and Immunology
    1. 5.1 Macrophages
    2. 5.2 Interleukins
    3. 5.3 T-cells
    4. 5.4 Dendritic cells
    5. 5.5 Inflammation
    6. 5.6 Adaptive Immunity
    7. 5.7 Usage against Colds
  6. 6 Interactions with Exercise Performance
    1. 6.1 Exercise-induced Immunosuppression
    2. 6.2 Red Blood Cells
    3. 6.3 Aerobic Capacity
  7. 7 Interactions with Hormones
    1. 7.1 Prolactin
  8. 8 Interactions with Oxidation
    1. 8.1 Mechanisms
  9. 9 Interactions with Organ Systems
    1. 9.1 Lungs and Airway
  10. 10 Nutrient-Nutrient Interactions
    1. 10.1 Itself
  11. 11 Nutrient Comparisons
    1. 11.1 Panax Ginseng
    2. 11.2 Ashwagandha
    3. 11.3 Bacopa Monnieri
    4. 11.4 Kan Jang
  12. 12 Safety and Toxicology
    1. 12.1 General
    2. 12.2 Case Studies

Don't Miss an Update!

Your e-mail is safe with us. We don’t share personal data.

1Sources and Composition

1.1. Sources

Echinacea is a term used to refer to a genus of purple cone flowers (belonging to the family Asteraceae) wth 9 known species,[5] the most common being purpurea and two other commonly used species being angustifolia and pallida. Echinacea is said to have a fiery and pungent taste[6] and has historical usage in north american medicine (for the alleviation of pain and the promotion of healing of snake bites, burns, cough, sore throats, and toothache[6]).

Echinacea is most commonly used as a herbal immunostimulant and for the purposes of fighting respiratory ailments and and flu symptoms,[5] and appears to be one of the more popular supplements used in US, Australia, and becoming more popular in North Africa, South America, and China in general (data derived from conference presentations cited via here[7]). It is used for purposes such as cold and general sickness prevention,[8] sometimes used in cancer patients alongside chemotherapy or after remission,[9][10][11] and sometimes by athletes for both lung health and attenuated exercise-induced immunosuppression.[12][13]

The German Monograph issued by the E Commission (book, cited via here[5]) recommends alcoholic extracts from the root of Echinacea pallida or juices pressed from the leaves and stems.

Echinacea is a highly popular 'immunostimulant' herb taken for the common cold, and the term 'echinacea' refers to a plant genera with a few species all being used commonly (purpurea, augustifolia, and pallida)

1.2. Composition

Echinacea (purpurea unless otherwise specified) tends to contain:

The alklymaide content (35.9mcg/g in Echinaforce[14] and up to 2.108mg/g of the dry weight of echinacea purpurea[15]) of:

  • Dodeca-2E,4E,8Z,10Z-tetraenoic acid and Dodeca-2E,4E,8Z,10E-tetraenoic acid (pair of structurally related isomers[14] totalling 1.44+/-1.00mg/g dry weight[15]) as well as both Dodeca-2E,4E,8Z-trienoic acid (0.10+/-0.11mg/g) and Dodeca-2E,4E-dienoic acid (0.06+/-0.05mg/g) being the most well known three alkylamides[14]

  • Undeca-2E,4E-diene-8,10-diynoic acid isobutylamide(purpurea[16] and atrorubens[17]) as well as its isomer Undeca-2E,4Z-diene-8,10-diynoic acid isobutylamide (0.21+/-0.15mg/g dry weight[15])

  • Undeca-2Z,4E-diene-8,10-diynoic acid 2-methylbutylamide (purpurea[18] at 0.07+/-0.05mg/g dry weight[15]) and undeca-2Z,4E-diene-8,10-diynoic acid isobutylamide (0.57+/-0.26mg/g dry weight[15])

  • Dodeca-2E,4Z,10Z-trien-8-ynoic acid isobutylamide(purpurea[16] and augustifolia[19][20])

  • Dodeca-2Z,4E,10Z-trien-8-ynoic acid isobutylamide (purpurea[16] and augustifolia[21])

  • Dodeca-2E,4E-diene-8,10-diynoic acid isobutylamide (purpurea[16] and achilles[16]), its isomer Dodeca-2E,4Z-diene-8,10-diynoic acid isobutylamide(0.42+/-0.19mg/g dry weight),[15] Dodeca-2Z,4E-diene-8,10-diynoic acid isobutylamide (0.16+/-0.09mg/g dry weight[15])

  • Dodeca-2E,4E-diene-8,10-diynoic acid 2-methylbutylamide (0.25+/-0.12mg/g dry weight[15]), dodeca-2Z,4E-diene-8,10-diynoic acid 2-methylbutylamide (unquantifiably low[15]), and dodeca-2E,4Z-diene-8,10-diynoic acid 2-methylbutylamide (0.04+/-0.03mg/g dry weight[15])

  • Pentadeca-8Z-ene-11,13-diyn-2-one (0.64+/-0.34mg/g dry weight), pentadeca-2E,9Z-diene-12,14-diynoic acid isobutylamide (1.04+/-0.67mg/g dry weight), and pentadeca-8Z,13Z-dien-11-yn-2-one (4.77+/-2.08mg/g dry weight) in pallida only[15]

  • The isomer mixture of pentadeca-8Z,11Z,13E-trien-2-one and pentadeca-8Z,11E,13Z-trien-2-one totalling 1.18+/-0.67mg/g (pallida only)[15]

A large amount of alkylamides (structure of the group) which are mostly either isobutylamides or methylbutylamides (subclassifications). Many of these structures exist in isomer pairs, where the only structural difference is an E or Z designation on a double bond. The exact 'active' molecule, or whether synergism between isomers causative of effects, are not known although the entire class of alkylamides appears to be the molecules causative of echinacea's effects

With other phytochemicals of:

  • Caffeic acid[7]

  • Echinacoside (6.9mcg/g in Echinaforce[14]), a triglycoside (glucose bound to two rhamnose molecules) with two caffeic acid molecules attached, found at 0.88+/-0.54mg/g in purpurea and 0.71+/-0.73mg/g pallida[15]

  • Cichoric acid, a tartaric acid molecule with two bound caffeic acid molecules (313.8mcg/g in Echinaforce[14] with 2.87+/-0.96mg/g dry weight of purpurea and 0.27+/-0.17mg/g in pallida[15], increased to 13.6+/-3.9mg/g in an 80% ethanolic extract of purpurea[7])

  • Cynarine (quinic acid bound to two caffeic acid molecules)

  • Chlorogenic Acid (40.2mcg/g in Echinaforce[14]) at 0.06+/-0.05mg/g in purpurea and not detected in pallida[15]

  • Caftaric acid (264.4mcg/g in Echinaforce[14])[15] at 0.15+/-0.06 in purpurea and 0.04+/-0.02 in pallida[15]

  • 9,9′-diisovaleroxy nitidanin (Neolignan)[16]

  • 2, 3-di-O-isoferuloyltartaric acid[22]

  • 2-O-caffeoyl-3-O-isoferuloyltartaric[22]

  • 1β-hydroxy-4(15),5E,10(14)-germacratriene (sequesterpene)[16]

  • Quercetin, the 3-O-rhamnosyl-(1→6)-galactoside glycoside, and Rutin[23]

  • Kaempferol as 3-O-rhamnosyl-(1→6)-galactoside[23]

  • Hypoxanthine[23]

The other molecules in echinacea are mostly related to caffeic acid (small phenolic molecule common in the plant kingdom) or structures consisting of caffeic acid and either sugars or other small phenolics (tartaric and quinic acid). These are not thought to underlie the effects of echinacea although they are present in supplements

Most of the above molecules are somewhat lipophilic, present in high quantities in 50-80% ethanolic extracts relative to water extracts.[7][18] Similar to most plants, echinacea bioactives vary depending on season and growing conditions.[15]

Echinacea also contains a carbohydrate (polysaccharide) content that is immunostimulatory in vitro and in some animal models, with a potency slightly less than that of Astragalus membranaceus (25-50mcg/mL) but comparable to that of wolfberry and kelp (Laminaria japonica).[24] The polysaccharides have shown immunopotentiating potential when given alongside a vaccine in animals[24] and has been noted to work with the flu vaccination[25] (data is not unanimous, as one study noted that in their model echinacea was ineffective[26]).

When comparing species of echinacea against one other, pallida appears to have a lesser overall alkylamide content than purpurea although the latter is comparable to augustifolia.[27]pallida appears to be comparatively high in ketoalkene and ketoalkyne structures rather than alkylamides, which are more related to cancer cytotoxicity than immunity.[28] Echinacoside (a caffeic acid glycoside) which sometimes appears to be in large quantities in pallida but not purpurea (sometimes[29] but not always so,[15] it does not have inherent immunostimulating properties[30]), and is an chemical indicator of species alongside cichoric acid (high in purpurea);[29] although augustifolia and purpurea are somewhat interchangeable, pallida does not appear to be.

There appears to be a component of Braun-type lipoproteins[31] (also seen in Spirulina) that are causative of the majority (85-98%) of the immunostimulating properties associated with echinacea in vitro[31][32] and removal of these Braun-type lipoproteins and any lipopolysaccharide (LPS) content abolishes the monocyte stimulating activity (via NF-kB activation) of echinacea.[31] It should be noted that some alkylamides are also active in this regard, and although LPS contamination appears to be a significant confound it may not be solely responsible (endotoxin free echinacea has also been implicated in immunostimulation[33])

Bacterial and LPS content in echinacea may underlie a good deal of (but not all) of macrophage stimulation from echinacea supplementation

1.3. Stability and Properties

Basic drying of echinacea (in processing after harvest) is associated with losses of bioactive molecules with chicoric acid being most susceptable to loss,[34][35] alkylamides have been implicated in this loss[34] although they are not lost as reliably (sometimes no loss is detected).[36] Chicoric acid has also been noted to be lost at storage conditions of 40°C when in the dried root, but in powder form the major alkylamide isomer pair appears unstable;[37] although only after heating processes (as the fresh plant at 20°C storage does not show alkylamide loss[38]) both chicoric acid and the alkylamide isomer pair are stable at -20°C[37] and 5°C when stored in the dark.[38]

High pressure pasteurization (HPP) of echinacea to remove bacterial contamination (Escherichia coli (E. coli) and Listeria monocytogenes[39]) does not significantly influence the content of phenolics (chicoric, caftaric, and chlorogenic acid) with the alkylamide content also similarly unaffected.[40] This is thought to be due to HPP preserving hydrogen bonds which are normally broken during heating processes or drying.[41]

It may be prudent to store processed echinacea products in cool and dark areas to avoid loss of alkylamides and phenolics (Note: inside a bottle of pills is already dark, temperature is the only factor to be concerned with at this stage)

1.4. Brand Name Products

Echinaforce is a hydroalcoholic extract of echinacea purpurea consisting of the herb and roots in a 95:5 ratio;[14][42] one study has detected that Caffeic acid, cynarin and polysaccharide are not detectable in Echinaforice.[14] Echinaforce appears to be free of endotoxin (lipopolysaccharide) content.[43][44] Despite the insignificant concentration of endotoxins such as LPS (which are highly correlated with macrophage stimulation from echinacea products[31][32]) Echinaforce has at least once been connected to reduced cold symptoms.[33]

Echinaforce is a standardized product of echinacea which appears to be free of endotoxin (LPS) contamination, with a higher than normal concentration of some alkylamides and no detectable cyanarin or caffeic acid. Although there does not appear to be variability associated with the effects of it, there is probably not enough evidence to conclude that it is more reliable

Echinaguard and Echinacin, common branded names, have been found to not be significantly different from trial using basic plant extracts (without brand name) as assessed by one meta-analysis able to do a subgroup analysis on brands.[45]

Echinaguard and Echinacin are two common brand names which do not have enough evidence to support their usage as better than the basic plant extract of either echinacea purpurea or augustifolia; essentially they are interchangeable


2.1. Absorption

In isolated Caco-2 cells, there does not appear to be significant uptake of the caffeic acid derivatives of echinacea (caftaric acid, echinacoside, cichoric acid) while alkylamides have a time-dependent uptake; the degree of uptake varied slightly over 90 minutes depending on the alkylamide in question and varied between 100% ((2E,4Z)-N-isobutylundeca-2,4-diene-8,10-diynamide) and 20% (, (2E,9Z)-N-(2-methylbutyl)pentadeca-2,9-diene-12,14-diynamide).[46] Overall, more than 50% of total alklyamides are absorbed within 90 minutes, and the major alkylamide of echinacea ((2E,4E,8Z,10Z)-N-isobutyldodeca-2,4,8,10-tetraenamide) appears to be absorbed to around 74+/-22%.[46] The transport of alkylamides has been confirmed when derived from other echinacea species,[47] and coingestion of multiple alkylamides has the potential for increasing the bioavailability of others (via sacrificial P450 metabolism).[48][49]

Alkylamides appear to be absorbed, with the degree of absorption varying depending on the alkylamide in question. Other molecules in echinacea do not appear to be well absorbed

2.2. Serum

Following oral administration of echinacea, the circulating concentration of the main alkylamide isomer pair (dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides) has been detected at 10.88ng/mL following ingestion of 2.5mL of echinacea tincture (60% ethanolic extract from echinacea augustifolia; oral dose of alkylamides not given but a 77:1 concentration for the production was noted) with a Tmax (time to peak serum levels) being in between 10-30 minutes.[50] Other alkylamides were detected in serum at a similar Tmax including the undeca-2E/Z-ene-8,10-diynoic acid-isobutylamides isomer pair (1.87ng/mL), dodeca-2E,4Z-diene-8,10-diynoic acid-isobutylamide (1.54ng/mL), dodeca-2E-ene-8,10-diynic acid-isobutylamide (0.96ng/mL), and dodeca-2E,4E,8Z-trienoic acid-isobutylamide (2.1ng/mL), while dodeca-2E,4E-dienoic acid-isobutylamide was not detected (limit of detection being 3pg/mL).[50]

Comparison of tablets versus tinctures has noted a more rapid absorption and higher Cmax associted with tincture (0.40ng/mL at 30 minutes) relative to capsules (0.12ng/mL at 45 minutes) although this study also failed to note any significant differences on measured immune parameters.[43] Another study using tablets has noted slower pharamcokinetic parameters with a Tmax of 2.3 hours, when measuring total alkylamides the serum level was 336+/-131ng/mL after acute ingestion of 625mg purpurea and 600mg augustifolia.[51]

Studies that assess interindividual variability note a large degree of variation, with a sample of three person varying Cmax values between 0.012-0.181ng/mL (main isomer pair following 20 drops of tincture as Echinaforce)[52]

Alkylamides can be detected in serum following oral ingestion of echinacea supplements, and absorption seems quite rapid. Circulating levels of alklyamides are all in the low nanomolar range. Both tinctures as well as capsules appear to increase serum levels, although tinctures may be faster absorbed possibly due to buccal absorption (through the mouth into the blood)

2.3. Enzymatic Interactions

Echinacea purpurea at 1600mg (four divided doses of 400mg) in humans has been found to significantly but modestly inhibit CYP2C9 (tolbutamide clearance reduced by 11% on average, 2/12 persons experiencing 25%), inhibited the aromatase enzyme (CYP1A2) as plasma Caffeine levels increased 27-30%, and induced CYP3A4 as serum midazolam clearance 42% relative to control.[53] Oddly, CYP3A4 appeared to be inhibited in the intestines as oral bioavailability of midozolam increased.[53] A 28 day study using 1600mg echinacea purpurea has failed to note any interaction with CYP3A4, CYP2E1, or CYP2D6[54] (previous study noted no acute effects on CYP2D6[53] and a standardized supplement of 801mg echinacea and 6.6mg isobutylamides also failed[55]) while there was a minor inhibitory effect of echinacea on CYP1A2 that failed to reach significance.[54]

1500mg echinacea purpurea daily for 14 days in combination with retroviral therapy (for HIV; protease inhibitor/ritonavir combination therapy) failed to note significant inhibition of the CYP3A4 enzyme, but this study is somewhat confounded as ritonavir itself is a CYP3A4 inhibitor and could outcompete echinacea.[56] Some decline in serum darunavir following exposure to echinacea after 14 days suggests induction of CYP3A4,[56] although another study in healthy persons given darunavir/ritonavir for 14 days alongside the same dose of echinacea failed to find any influence on circulating levels of these two drugs despite inducing CYP3A4 (midozolam probe).[57]

2 weeks of pretreatment with a very high dose of echinacea (5100mg conferring 23mg akylamides) noted a small but significant increase in serum (S)-warfarin concentrations (9%, 95% CI of 1-18%)[58] that does not appear to be clinically relevant according to a review on the topic.[5] This is indicative of CYP2C9 and CYP3A4 inhibition.[59]

In regards to P450 enzymes of importance to drug-herb interactions, there appears to be minor inhibition of aromatase (CYP1A2) and some possible relevant interactions with both CYP3A4 (inhibition and induction acutely, over the long term appears to increase enzyme activity) and CYP2C9 (minor inhibition); CYP2D6 does not appear affected

One study using 801mg echinacea purpurea (6.6mg isobutylamides) for 14 days failed to have any significant effect on P-glycoprotein[5] despite some of the alkylamides showing inhibition in vitro.[60] Both echinacea pallida and sanguinea have been noted to inhibit P-glycoprotein.[61]

No significant effect on P-glycoprotein following ingestion of standard echinacea supplementation, although some possible interactions have been noted ex vivo and with other species


3.1. Cannabinoid

Concentrations of 10-25mcg/mL echinacea appear to stimulante TNF-α production in vitro with macrophages and monocytes (25mcg leading to 11-fold induction of TNF-α protein content and 8-fold induction of mRNA); it was not additive with LPS (which inhernetly induced TNF-α) and mediated TNF-α via cAMP-sensitive and CB2-dependent mechanisms (signalling via CB2 dependent on NF-kB, JNK/ATF-2 and CREB-1).[44] The potency was in the nanomolar concentration range (1µM being effective, EC50 values not determined), with the isomer pair dodeca-2E,4E,8Z,10E-tetraenoic acid(s) and dodeca-2E,4E-dienoic being most active and cichoric acid ineffective.[44] There appears to be more affinity for CB2 relative to CB1 associated with echinacea alkylamides, and CB2 receptors are more highly expressed on immune cells (whereas CB1 receptors are highly localized on neurons).[62]

One study suggested that intracellular rises in Ca2+ are noted with alkylamides via CB2 receptor activation (HL60 cells)[63] although a later study noted that this may be due to a CB-independnet mechanism (rise seen in HEK293 which do not express CB2 receptors).[6]

Binding to and activation of the CB2 receptor (the cannabinoid receptor expressed on immune cells mostly) has been noted with alkylamides in echinacea, while there does appear to be a degree of binding to the CB1 receptor although it is comparatively less

For studies that do report EC50 values, they are highly variable depending on whether an isolated alkylamide is tested or a mixture is with reports ranging from 60nM[64] to 2-20μM[65] (30-fold difference in potency). The isomer mixture (dodeca-2E,4E,8Z,10E-tetraenoic acids) displays additive agonistic effects to 9% of the receptor capability at (The reference agonist, arachidonyl-2′-chloroethylamide, activated 47% of the receptor capability) and the neolignan 9,9′-diisovaleroxy nitidanin also activates cannabinoid receptors.[16] However, a variety of compounds in echinacea appear to have weak inverse agonist properties.[16]

Due to various alkylamides having differing effects on cannabinoid receptors (agonistic, antagonistic, or inverse agonistic) and the relative inefficacy overall, it is unlikely that echinacea-derived alkylamides possess neural properties like those seen with Marijuana

3.2. Anxiety

It is though that echinacea may reduce anxiety (as CB1 receptor activation reduces anxiety[66] while echinacea has been noted to inhibit fatty acid (FAAH)[67] which degrades anandamide,[68] an endogenously produced cannabinoid) and when tested in 22 otherwise healthy adults assessed by the State-Trait Anxiety Inventory (STAI) noted that 40mg of echinacea augustifolia was able to significantly reduce anxiety (20mg ineffective, higher doses not tested) with the average STAI score being reduced from slightly over 120 to 100.[69] A rat study conducted prior to the human intervention noted that 4-5mg/kg was associated with the best anxiolytic effects (human equivalent of 0.64-0.8mg/kg).[69]

One study has noted a significant reduction in anxiety associated with very low oral doses of echinacea tablets

As a bell curve was noted with this study, it is unsure if higher doses will have a similar effect; replication of this study would also be prudent

4Cardiovascular Health

4.1. Blood Pressure

A study assessing an acute dose of echinacea at 350mg failed to find evidence of echinacea altering blood pressure.[70]

No currently known interactions with blood pressure

5Inflammation and Immunology

5.1. Macrophages

The alkylamides in echinacea are known to activate cannabinoid receptors with more affinity for CB2 relative to CB1, with the former being highly expressed on immune cells[71] and a solution of alkylamides being able to activate CB2 on monocytes and macrophages with an EC50 of less than 1µM[44] (overall, the EC50 is somwhat variable, between 60nM[64] and 20µM[65] possible due to various different ratios of alkylamides and testing conditions).

Secondary to activating the second subset of the cannabinoid receptors (CB2), some alkylamides can induce TNF-α release in macrophages and monocytes.[44] The release of TNF-α appears to be secondary to NF-kB activation, JNK/ATF-2 and CREB-1 as intermediates, and is additionally cAMP dependent.[44]

Some potential immunostimulatory effects of echinacea not due to LPS, but secondary to alkylamides, from activation of cannabinoid receptors that increases TNF-α levels. The concentration of which this occurs may be biologically relevant

TNF-α induction has been noted at low concentrations when the alkylamides are fed to rats at 12mcg/kg[72] and is achieved in isolated macrophages via TLR4 dependent and independent mechanisms.[73] The activation of macrophages from echinacea alkylamides[73] is sometimes seen as a modulating effect, since overall NF-kB activation in macrophages treated with both LPS and echinacea is less than that seen with LPS alone.[74]

One study using endotoxin-free echinacea purpurea has noted a reduction in TNF-α release by 24% from PBMCs taken from persons fed echinacea (4mL of Echinaforce for 3 days, followed by 10mL for 3 days).[14] This may be related to total bacterial load highly correlating with TNF-α induction.[32][31][75] The more common endotoxin contaminant known as lipopolysaccharide (LPS) is a proinflammatory reference molecule that induces macrophage activation via the TLR4 receptor.[76]

When assessing TNF-α induction in vitro, it appears that purpurea is significantly outperformed by pallida, although this study noted a failure of both purpurea and augustifolia to induce TNF-α acutely in PBMCs.[77]

While alkylamides in echinacea either alternatively activate or suppress macrophages activation while LPS contamination induces macrophages activity via TLR4 (classical activation pathway), the practical effects of orally ingested echinacea on macrophages is unclear. The overall effect could be one where there is a macrophage stimulatory effect without LPS contamination and a controlled stimulation with coincubation of echinacea and LPS (a similar modulatory effect has been seen with Ganoderma lucidum)

5.2. Interleukins

The induction of IL-8, as well as IL-6, appear to hold consistenly when the dose is changed in vitro in leukocytes.[78]

Endotoxin-free echinacea has been noted to reduce IL-1β secretion from PMBCs while increasing IL-10 by approximately 13%, with weak induction of IFN-γ and IL-8 (cells taken from persons fed 4mL Echinaforce for 3 days and 10mL for another 3 days).[14] The induction of IL-10 appears to be comparatively higher with pallida and laevigata relative to purpurea when tested in isolated PMBCs,[77]

5.3. T-cells

In the presence of a mitogen (Phaseolus vulgaris haemagglutinin), echinacea appears to stimulate the lymphocyte proliferation response in mice[79] which may be general as it has been noted with all common species of echinacea in response to sheep red blood cells (mice);[80] lymphocyte proliferation has been noted in vitro with alkylamides at 50mcg/mL,[81]in vivo with a notable increase in CD4+ lymphocytes,[82] and in vitro by stimulating interferon IFNγ production in anti-CD3-treated murine T-cell cultures.[83]

Despite this, echinacea juice (leaf) supplementation appears to slightly suppress T-cell levels (6%)[84] and beyond suppressing T-cell release of IL-2,[81] TNF-α and IL-1β[80] there might be reduced antigen uptake from dendritic cells by T-cells.[23]

Mixed effects observed on T lymphocytes. Although some stimulatory effects are noted, in practical situations there is a very slight suppression of T-cell count without significant alteration of the subpopulations

5.4. Dendritic cells

Dendritic cells are antigen present cells mediating innate and adaptive immunity that play a role in presenting antigens to T-cells for recognization.[85] Their activation and proliferation, coupled with increased activity of T-cells, leads to greater antigen recognition and adaptive immunity (in response to sickness).[85]

The basic root extract (polysaccharides, mostly glucitol acetate and mannitol acetate) can increase the content of CD86 and CD54 positive cells in a concentration-dependent manner, increasing from 10% to 25% and 27% (CD86) and from 12% to 30% and 32% (CD54).[23] The leaf extract appeared to actually reduce content of CD86, CD54, and MHC II relatively, due to a large induction of CD11c+ BMDCs. An induction of CD54 has been noted elsewhere with an ethanolic root extract alongside a general stimulatory effect.[86]

The leaf extract (more commonly used) is known to concentration-dependently increase CD11c+ BMDCs from 75% in the control to 94% (50mcg/mL) and 100% (150mcg/mL) while the root extract was less effective; due to a reduction in other positive cells (CD86, CD54, MHC II) the relative expression was approximately doubled.[23] A reduction of CD86 has been noted with the leaf extract elsewhere,[86]

Differential effects have also been noted on CD83+ cells, being stimulated with a butanolic extract (both stems and roots) and suppressed with an ethyl acetate fraction.[87]

When assessing antigen uptake by dendritic cells, both the root and leaf extract appear to significantly reduce antigen uptake and acted to inhibit interactions between dendritic cells and CD4+ T cells.[23] The authors hypothesized (as suppression was noted with both root and leaf extracts, while roots stimulated dendritic cell activity) that this may be due to T-cell suppression (noted elsewhere[81]).

Although the evidence is a bit unclear, it appears that the polysaccharide fragment may induce dendritic cell activity while the alkylamides (in the leaf extract and more commonly supplemented) may suppress dendritic cell activity; both appear to reduce activity of a dendritic cell and T-cell interaction, which may be due to the effects observed on T-cells

5.5. Inflammation

Mechanistically, Cynarin is known to be immunosuppressive[88] (although the low concentration in echinacea may preclude any efficacy of this ingredient) and extracts of echinacea appear to modulate NF-kB activity in dendritic cells[89]

The leaf extract has been known to attenuate COX2 induction, with 2-8mcg/mL of the extract (but not root) reducing COX2 induction in a concentration dependent manner in the range of 28-85%; COX1 was unaffected.[23]

The essential oil of echinacea purpurea has been found to possess anti-inflammatory effects in vivo as assessed by the granulation formation test (28.52%), paw edema (48.51%), and ear edema (44.79% inhibition).[90]

Extracts of echinacea appear to have anti-inflammatory effects following oral ingestion, but the potency does not appear to be overly remarkable

5.6. Adaptive Immunity

Increased production of antigen specific immunoglobulins M and G has been noted in rats following ingestion of echinacea (augustifolia), with more significance for the increase in IgG to 34.6% more than control (measured on day 20, the first point where results were consistently statistically significant).[91]

May increase the antigen count in the body, which is a possible mechanism for fighting off acute sickness

5.7. Usage against Colds

A systemic review[92] (assessing several meta-analyses[45][93][94]) noted that despite fairly well structured studies (average Jadad score[95] of 3.5) there was poor standardization of test product used (studies more likely than not used echinacea purpurea and more likely than not used the aerial parts, but data is frequency absent).[92] Despite these potential concerns, previous meta-analyses have concluded a 58% reduced risk of developing cold symptoms (Odds Ratio (OR) 0.42; 95% Confidence Interval (CI) of 0.25-0.71) and 1.4 less cold days on average,[45] placebo being associated with 55% the risk of colds relative to echinacea (OR 1.55 and 95% CI of 1.02-2.36),[93] but the Cochrane analysis of randomized blinded trials noted that the large hetereogeneity observed prevented significant benefit from being associated with echinacea.[94]

One particular meta-analysis[45] that noted a 58% (95% CI of 29-75%) reduction in cold occurrence and 1.4 days less average cold reduction noted that, while all but one study[96] had a mean value in the positive range (indicative of less cold occurrence) many studies in isolation crossed the zero point and were statistically insignificant, only reaching significance after pooling.[45] Another meta-analysis with more restrictive inclusion criteria attempting to do the same failed to find significant benefit associated with echinacea over placebo.[94]

In general, although there is benefit associated with echinacea supplementation for the prevention of colds that is greater than placebo this appears to be highly variable. Meta-analysis of trials is somewhat limited due to large variations seen in trials on echinacea by using different doses, product formulations, and time frames

When isolated studies that use tinctures of echinacea, 2.5mL thrice daily (7.5mL daily, brand Echinaguard) for one week prior to and 5 days after inoculation with the common cold (rhinovirus 39) noted that the rate of cold development occurred in 82% of placebo and only 58% of persons with echinacea;[97] this trial design has been used with encapsulated echinacea (300mg thrice a day) without effect, although this study used echinacea angustifolia.[98] Two studies exist using 8mL of a tincture for either 28 days[99] or 8 weeks[100] in healthy persons have noted an increase in immunity after exercise and no effect on cold occurrence, respectively. When used prophylactically (daily in prevention of colds) echinacea daily for 4 months appears to be more effective than placebo even at 0.9mL thrice daily (using the brand name Echinaforce).[101]

In persons already with a cold, children (7.5-10mL daily for 10 days) failed to find benefit with echinacea supplementation when given to children already with a cold[96] while adults order to take 5mL twice a day for 10 days at the first signs of a cold noted some protective effects associated with supplementation.[102] One study not located online by cited in meta-analysis[45] (Braunig and Knick, 1993) has been noted to skew a meta-analysis due to its effect size, where the reduction in cold time reached –3.80 days (95% CI of 3.08-4.52 day reduction) where most other studies noted a day or so reduction.

When looking solely at tincture using studies, the effects appear to be somewhat similar to encapsulated power echinacea (still just as variable as echinacea usage)

A few studies assessing echinacea are confounded with either the inclusion of propolis and Vitamin C,[1] Thyme and peppermint,[2] lemongrass and spearmint,[3] and Vitamin C with rosemary and Fennel Essential Oil (not located online, assessed via meta-analysis[45]); these studies are excluded from the above analysis due to being confounded.

6Interactions with Exercise Performance

6.1. Exercise-induced Immunosuppression

Echinacea appears to be commonly used by athletes for the purpose of preventing exercise-induced immunosuppression[103] although several reviews note a lack of evidence to support usage.[104][105]

At least one study noted a low rate of sickness in athletes using echinacea (although limited by no control as well as being open-label)[106] and another study has noted that the significant reductions in salivary s-IgA (thought to be indicative of immunity suppression from exercise when reduced) were attenuated with echinacea, and although there were no significant differences in frequency of sickness during the 4 week trial the echinacea group reported reduced sickness duration.[107]

Insufficient evidence to support a role of echinacea supplementation in preventing sickness from exercise-induced immunosuppression

6.2. Red Blood Cells

An increase in oxygen carrying capacity of the blood secondary to inducing erythroid growth factors such as the hormone erythropoetin has been noted in animal models[108] and 8,000mg of echinacea purpurea daily for 28 days is associated with increased erythropoetin levels (in the range of 77-94% increases from weeks 1-3, declining at week 4) without significantly influence RBC count.[109] This study appears to have been duplicated in Medline.[4]

Appears to increase erythropoetin levels following oral administration, but this does not appear to be associated with any significant increases in hemoglobin or RBC count

6.3. Aerobic Capacity

It has been noted that supplementation of echinacea at the equivalent of 3,200mg daily for 30 days (in a study assessing Eleutherococcus senticosus and using echinacea as a comparator) trended to increase maximal oxygen consumption (VO2 max) in untrained subject (5%) but failed to be significant[110] while a later study using a much higher dose (8,000mg; 2,000mg four times daily) for 4 weeks in recreationally active men was noted to increase VO2 max and decrease the oxygen requirement of exercise without affecting heart rate.[109]

It was thought that echinacea can increase red blood cell count and thereby increase oxygen carrying capacity and exercise performance, although the study to note improved exercise performance did not detect such an increase in RBC (only an increase in erythropoetin).[109]

High doses may aid cardiovascular exercise, thought to be secondary to increasing the oxygen carrying capacity of the blood. Requires more evidence to support this position

7Interactions with Hormones

7.1. Prolactin

Echinacea purpurea has been noted to reduce prolactin levels over 15 days in male rats at 100mg/kg, with 30mg/kg being ineffective.[111]

8Interactions with Oxidation

8.1. Mechanisms

Relative to other herbs on a dry weight basis, echinacea appears to generally underperform and inhernetly has weak to moderate effects.[112][113][114][115][116]

The anti-oxidant potential of chicoric acid (2R,3R-dicaffeoyl tartaric acid) appears to be comparable to that of Rosmarinic Acid (caffeic acid bound to 3,4-dihydroxyphenyl lactic acid) on a weight basis,[117] with the alkylamide being weaker and 24uM being required to be as effective as 1uM rosmarinic acid;[7] chicoric acid appears to be increased in antioxidative potenty when combined with either alkylamides or polysaccharides from echinacea, and combination of all three outperformed any combination of two agents.[7]

Although echinacea appears to be synergistic with itself when it comes to antioxidative properties, it does not appear to have more antioxidative potential in vitro relative to other supplemental herbs

9Interactions with Organ Systems

9.1. Lungs and Airway

In an ex vivo model of lung function (3-dimensional organotypic model) infected with the common cold, echinacea has been noted to reduce mucus production and to abolish the increase in IL-6 and IL-8 seen with rhinovirus administration without affecting lung structure or histology.[118]

Oral ingestion of echinacea in mice has been noted to increase the macrophage activity in lung tissue in a dose dependent manner with significant occurring at an alkylamide and polysaccharide intake of 80mcg/kg and 20mg/kg, respectively.[119] Oral intake of echinacea does not appear to be able to influence viral concentration in lung tissue of animals with the flu despite being noted to lower inflammatory cytokines (IFNγ and IL-10)[120] and aiding the course of symptoms in mice.[121]

There appear to be beneficial effects of echinacea supplementation on the lungs and airway, although the practical relevance of this animal data to humans is not certain

10Nutrient-Nutrient Interactions

10.1. Itself

When the alkylamide are incubated with oxidized LDL (and exert relatively weak anti-oxidant effects), there appear to be synergistic antioxidant effects when coincubated with either free caffeic acid or a source of caffeic acid (chicoric acid or echinacoside).[7] This synergism was built off of previous research noting more antioxitive effects with chicoric acid and alkylamides,[117] and the synergism with alkylamides is also seen with a combination of chicoric acid and the polysaccharides from echinacea.

Coingestion of multiple alkylamides also has the potential for increasing the bioavailability of others (via sacrificial P450 metabolism)[48][49] which theoretically increases absorption of echinacea alkylamides when consumed in combination relative to in isolation.

11Nutrient Comparisons

Due to the popularity of echinacea, it is sometimes used as a reference drug when assessing the potency of other compounds. For example, a study might use a true control group (no drug) and a reference drug group (echinacea) in order to best test the 'new' compound (Drug X).

If the test drug outperforms control or placebo, it is effective but might not be effective enough to displace the standard reference drug. If it outperforms the reference drug as well, it is more noteworthy

11.1. Panax Ginseng

In rat studies, induction of mRNA for TNF-α, IL-10, and TGF-β1 are comparable with echinacea (0.75g/kg) and Panax ginseng (0.50mg/kg) although some differences were observed at 20 days and no longer present at 40 days.[122]

11.2. Ashwagandha

A study feeding rats 1% of their feed as either echinacea (purpurea) or Ashwagandha (Withania somnifera at 3.6% withanoids and 1.1% alkaloids) for 4 weeks noted that there were no significant differences in any serum immunoglobulin (A, G, M, or E) although both groups appeared to increase levels of immunoglobulins relative to control.[123]

Echinacea secreted more IFN-γ and IL-2 than ashwagandha and less TNF-α, and this trend persisted after LPS and mitogen stimulation.[123]

11.3. Bacopa Monnieri

A study feeding rats 1% of their feed as either echinacea (purpurea) or Bacopa monnieri (12.8% saponins) for 4 weeks noted Bacopa was able to increase serum IgA and IgG to a higher degree than echinacea (32% and 102% more, respectively) while they performed equally on serum IgM and IgE.[123]

In response to Concavalin A and LPS, bacopa secreted more IL-6 relative to echinacea while there were no differences in IFN-γ and IL-2.[123]

11.4. Kan Jang

Kan Jang capsules are a Traditional Chinese Medicine consisting of Andrographis paniculata and Siberian Ginseng (Eleutherococcus senticosus). In comparison to a brand name called Immunal (Echinacea purpurea 20% ethanolic extract) in children (4-11yrs) with uncomplicated respiratory diseases noted that Kan Jang outperformed echinacea in regards to reducing symptoms associated with upper respiratory tract infection over 10 days of treatment.[124]

Kan Jang combination tablets have once been noted to outperform echinacea in regards to reducing symptoms assocaited with upper respiratory tract infection, although it should be noted the echinacea is not really too effective in reducing symptoms (being more associated with reduced risk of getting the symptoms instead) and this may have not been an accurate comparison

12Safety and Toxicology

12.1. General

In general, there do not appear to be clinically significant adverse effects associated with echinacea supplementation[125] which seem to be related to allergic reaction or rash.[126] One study looking at supplements which may be related to dry eyes noted that echinacea, as well as both Kava and niacin, were somewhat associated although causation could not be placed.[127]

Allergy to echinacea appears to be highly correlated with an allergy to ragweed, which can be used as an indicator of possible adverse effects to echinacea.[128]

In general there are no significant side effects with echinacea, although it is possible to be allergic to the plant genus. Allergies to echinacea appear to be correlated with allergies to ragweed, and thus those with allergies to ragweed may be at higher risk of allergic responses to supplemental echinacea

12.2. Case Studies

Ingestion of 5mL of a 40% ethanolic tincture (bioequivalent to 3825mg echinacea augustifolia and 150mg echinacea purpurea) caused immediate flushing, throat burning, urticaria and diarrhea that was successfully treated upon hospital administration and Promethazine which was thought to be assocaited with an allergic reaction to the herb;[129] other case studies have been reported where patients respond positively to allergic testing at later dates.[130]

It is possible to be allergic to echinacea supplementation

Scientific Support & Reference Citations


  1. Hermann R, von Richter O Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions . Planta Med. (2012)
  2. Wu L, et al Echinacea-induced cytosolic Ca2+ elevation in HEK293 . BMC Complement Altern Med. (2010)
  3. Dalby-Brown L, et al Synergistic antioxidative effects of alkamides, caffeic acid derivatives, and polysaccharide fractions from Echinacea purpurea on in vitro oxidation of human low-density lipoproteins . J Agric Food Chem. (2005)
  4. Najm W, Lie D Dietary supplements commonly used for prevention . Prim Care. (2008)
  5. Ma H, et al The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors--results of a prospective study . BMC Cancer. (2011)
  6. Bright-Gbebry M, et al Use of multivitamins, folic acid and herbal supplements among breast cancer survivors: the black women's health study . BMC Complement Altern Med. (2011)
  7. Engdal S, Klepp O, Nilsen OG Identification and exploration of herb-drug combinations used by cancer patients . Integr Cancer Ther. (2009)
  8. Walsh NP, et al Position statement. Part two: Maintaining immune health . Exerc Immunol Rev. (2011)
  9. Senchina DS, et al Herbal supplements and athlete immune function--what's proven, disproven, and unproven . Exerc Immunol Rev. (2009)
  10. Ritchie MR, et al Effects of Echinaforce® treatment on ex vivo-stimulated blood cells . Phytomedicine. (2011)
  11. Thomsen MO, et al Seasonal variations in the concentrations of lipophilic compounds and phenolic acids in the roots of Echinacea purpurea and Echinacea pallida . J Agric Food Chem. (2012)
  12. Hohmann J, et al Alkamides and a neolignan from Echinacea purpurea roots and the interaction of alkamides with G-protein-coupled cannabinoid receptors . Phytochemistry. (2011)
  13. The constituents of Echinacea atrorubens roots and aerial parts
  14. Spelman K, Wetschler MH, Cech NB Comparison of alkylamide yield in ethanolic extracts prepared from fresh versus dry Echinacea purpurea utilizing HPLC-ESI-MS . J Pharm Biomed Anal. (2009)
  15. TLC and HPLC Analysis of Alkamides in Echinacea Drugs
  16. Alkamides from the roots of Echinacea angustifolia
  17. Chen Y, et al Macrophage activating effects of new alkamides from the roots of Echinacea species . J Nat Prod. (2005)
  18. Lu Y, et al Efficient counter-current chromatographic isolation and structural identification of two new cinnamic acids from Echinacea purpurea . Nat Prod Commun. (2012)
  19. Benson JM, et al Echinacea purpurea extracts modulate murine dendritic cell fate and function . Food Chem Toxicol. (2010)
  20. Liu Y, et al Adjuvant activity of Chinese herbal polysaccharides in inactivated veterinary rabies vaccines . Int J Biol Macromol. (2012)
  21. Di Pierro F, et al Use of a standardized extract from Echinacea angustifolia (Polinacea) for the prevention of respiratory tract infections . Altern Med Rev. (2012)
  22. Ragupathi G, et al Evaluation of widely consumed botanicals as immunological adjuvants . Vaccine. (2008)
  23. TLC and HPLC Analysis of Alkamides in Echinacea Drugs
  24. Chicca A, et al Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida . Br J Pharmacol. (2008)
  25. Binns SE, et al Phytochemical variation in echinacea from roots and flowerheads of wild and cultivated populations . J Agric Food Chem. (2002)
  26. Rininger JA, et al Immunopharmacological activity of Echinacea preparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells . J Leukoc Biol. (2000)
  27. Pugh ND, et al The majority of in vitro macrophage activation exhibited by extracts of some immune enhancing botanicals is due to bacterial lipoproteins and lipopolysaccharides . Int Immunopharmacol. (2008)
  28. Pugh ND, Jackson CR, Pasco DS Total bacterial load within Echinacea purpurea, determined using a new PCR-based quantification method, is correlated with LPS levels and in vitro macrophage activity . Planta Med. (2013)
  29. Brinkeborn RM, Shah DV, Degenring FH Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial . Phytomedicine. (1999)
  30. Kim HO, et al Retention of alkamides in dried Echinacea purpurea . J Agric Food Chem. (2000)
  31. Kim HO, et al Retention of caffeic acid derivatives in dried Echinacea purpurea . J Agric Food Chem. (2000)
  32. Stuart DL, Wills RB Effect of drying temperature on alkylamide and cichoric acid concentrations of Echinacea purpurea . J Agric Food Chem. (2003)
  33. Livesey J, et al Effect of temperature on stability of marker constituents in Echinacea purpurea root formulations . Phytomedicine. (1999)
  34. Effect of handling and storage on alkylamides and cichoric acid in Echinacea purpurea
  35. Patterson MF Microbiology of pressure-treated foods . J Appl Microbiol. (2005)
  36. Chen XM, et al Effect of high pressure pasteurization on bacterial load and bioactivity of Echinacea purpurea . J Food Sci. (2010)
  37. Advantages of high pressure sterilisation on quality of food products
  38. Schapowal A Efficacy and safety of Echinaforce® in respiratory tract infections . Wien Med Wochenschr. (2013)
  39. Woelkart K, et al Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system . Int J Clin Pharmacol Ther. (2006)
  40. Gertsch J, et al Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways . FEBS Lett. (2004)
  41. Shah SA, et al Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis . Lancet Infect Dis. (2007)
  42. Matthias A, et al Permeability studies of alkylamides and caffeic acid conjugates from echinacea using a Caco-2 cell monolayer model . J Clin Pharm Ther. (2004)
  43. Jager H, et al Transport of alkamides from Echinacea species through Caco-2 monolayers . Planta Med. (2002)
  44. Matthias A, et al Bioavailability of Echinacea constituents: Caco-2 monolayers and pharmacokinetics of the alkylamides and caffeic acid conjugates . Molecules. (2005)
  45. Matthias A, et al Cytochrome P450 enzyme-mediated degradation of Echinacea alkylamides in human liver microsomes . Chem Biol Interact. (2005)
  46. Woelkart K, et al Bioavailability and pharmacokinetics of alkamides from the roots of Echinacea angustifolia in humans . J Clin Pharmacol. (2005)
  47. Matthias A, et al Echinacea alkamide disposition and pharmacokinetics in humans after tablet ingestion . Life Sci. (2005)
  48. Goey AK, et al The bioanalysis of the major Echinacea purpurea constituents dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides in human plasma using LC-MS/MS . J Chromatogr B Analyt Technol Biomed Life Sci. (2012)
  49. Gorski JC, et al The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo . Clin Pharmacol Ther. (2004)
  50. Gurley BJ, et al In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto . Clin Pharmacol Ther. (2004)
  51. Gurley BJ, et al Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea . Mol Nutr Food Res. (2008)
  52. Moltó J, et al Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients . Antimicrob Agents Chemother. (2011)
  53. Penzak SR, et al Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects . Pharmacotherapy. (2010)
  54. Abdul MI, et al Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects . Br J Clin Pharmacol. (2010)
  55. Wittkowsky AK Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions . Semin Vasc Med. (2003)
  56. Mahringer A, et al Alkamides from Echinacea angustifolia Interact with P-Glycoprotein of Primary Brain Capillary Endothelial Cells Isolated from Porcine Brain Blood Vessels . Planta Med. (2013)
  57. Qiang Z, et al Echinacea sanguinea and Echinacea pallida Extracts Stimulate Glucuronidation and Basolateral Transfer of Bauer Alkamides 8 and 10 and Ketone 24 and Inhibit P-glycoprotein Transporter in Caco-2 Cells . Planta Med. (2013)
  58. Woelkart K, et al The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots . Planta Med. (2005)
  59. Chicca A, et al Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts . Int Immunopharmacol. (2009)
  60. Raduner S, et al Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects . J Biol Chem. (2006)
  61. Woelkart K, Bauer R The role of alkamides as an active principle of echinacea . Planta Med. (2007)
  62. Haller J, et al The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety . Eur J Neurosci. (2002)
  63. Gertsch J Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system . Planta Med. (2008)
  64. Piomelli D, et al Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597) . CNS Drug Rev. (2006)
  65. Haller J, et al The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers . Phytother Res. (2013)
  66. Shah SA, et al Effects of echinacea on electrocardiographic and blood pressure measurements . Am J Health Syst Pharm. (2007)
  67. Pertwee RG The pharmacology of cannabinoid receptors and their ligands: an overview . Int J Obes (Lond). (2006)
  68. Goel V, et al Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats . Int Immunopharmacol. (2002)
  69. Sullivan AM, et al Echinacea-induced macrophage activation . Immunopharmacol Immunotoxicol. (2008)
  70. Stevenson LM, et al Modulation of macrophage immune responses by Echinacea . Molecules. (2005)
  71. Tamta H, et al Variability in in vitro macrophage activation by commercially diverse bulk echinacea plant material is predominantly due to bacterial lipoproteins and lipopolysaccharides . J Agric Food Chem. (2008)
  72. Rossol M, et al LPS-induced cytokine production in human monocytes and macrophages . Crit Rev Immunol. (2011)
  73. Senchina DS, et al Phytochemical and immunomodulatory properties of an Echinacea laevigata (Asteraceae) tincture . J Altern Complement Med. (2011)
  74. Kapai NA, et al Selective cytokine-inducing effects of low dose Echinacea . Bull Exp Biol Med. (2011)
  75. Skopińska-Rózewska E, et al Dose-dependent in vivo effect of Rhodiola and Echinacea on the mitogen-induced lymphocyte proliferation in mice . Pol J Vet Sci. (2011)
  76. Zhai Z, et al Enhancement of innate and adaptive immune functions by multiple Echinacea species . J Med Food. (2007)
  77. Sasagawa M, et al Echinacea alkylamides inhibit interleukin-2 production by Jurkat T cells . Int Immunopharmacol. (2006)
  78. Mishima S, et al Antioxidant and immuno-enhancing effects of Echinacea purpurea . Biol Pharm Bull. (2004)
  79. Morazzoni P, et al In vitro and in vivo immune stimulating effects of a new standardized Echinacea angustifolia root extract (Polinacea) . Fitoterapia. (2005)
  80. Schwarz E, et al 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)
  81. Banchereau J, et al Immunobiology of dendritic cells . Annu Rev Immunol. (2000)
  82. Wang CY, et al Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a cell- and gene-based study . Genomics. (2006)
  83. Wang CY, et al Genomics and proteomics of immune modulatory effects of a butanol fraction of echinacea purpurea in human dendritic cells . BMC Genomics. (2008)
  84. Dong GC, et al Blocking effect of an immuno-suppressive agent, cynarin, on CD28 of T-cell receptor . Pharm Res. (2009)
  85. Yin SY, et al Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses . BMC Genomics. (2010)
  86. Yu D, et al Anti-inflammatory effects of essential oil in Echinacea purpurea L . Pak J Pharm Sci. (2013)
  87. Rehman J, et al Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis . Immunol Lett. (1999)
  88. Woelkart K, Linde K, Bauer R Echinacea for preventing and treating the common cold . Planta Med. (2008)
  89. Schoop R, et al Echinacea in the prevention of induced rhinovirus colds: a meta-analysis . Clin Ther. (2006)
  90. Linde K, et al Echinacea for preventing and treating the common cold . Cochrane Database Syst Rev. (2006)
  91. Jadad AR, et al Assessing the quality of reports of randomized clinical trials: is blinding necessary . Control Clin Trials. (1996)
  92. Taylor JA, et al Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial . JAMA. (2003)
  93. Sperber SJ, et al Echinacea purpurea for prevention of experimental rhinovirus colds . Clin Infect Dis. (2004)
  94. Turner RB, et al An evaluation of Echinacea angustifolia in experimental rhinovirus infections . N Engl J Med. (2005)
  95. Influence of Echinacin (EC31) treatment on the exercise-induced immune response in athletes
  96. Grimm W, Müller 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)
  97. Jawad M, et al Safety and Efficacy Profile of Echinacea purpurea to Prevent Common Cold Episodes: A Randomized, Double-Blind, Placebo-Controlled Trial . Evid Based Complement Alternat Med. (2012)
  98. Schulten B, et al Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomised, double-blind clinical trial . Arzneimittelforschung. (2001)
  99. Cohen HA, et al Effectiveness of an herbal preparation containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study . Arch Pediatr Adolesc Med. (2004)
  100. Barrett BP, et al Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial . Ann Intern Med. (2002)
  101. Lindenmuth GF, Lindenmuth EB The efficacy of echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: a randomized, double-blind placebo-controlled study . J Altern Complement Med. (2000)
  102. Petróczi A, et al Limited agreement exists between rationale and practice in athletes' supplement use for maintenance of health: a retrospective study . Nutr J. (2007)
  103. Gleeson M, Lancaster GI, Bishop NC Nutritional strategies to minimise exercise-induced immunosuppression in athletes . Can J Appl Physiol. (2001)
  104. Gleeson M, Nieman DC, Pedersen BK Exercise, nutrition and immune function . J Sports Sci. (2004)
  105. Schoop R, Büechi S, Suter A Open, multicenter study to evaluate the tolerability and efficacy of Echinaforce Forte tablets in athletes . Adv Ther. (2006)
  106. Hall H, Fahlman MM, Engels HJ Echinacea purpurea and mucosal immunity . Int J Sports Med. (2007)
  107. 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. (2002)
  108. Whitehead MT, et al Running economy and maximal oxygen consumption after 4 weeks of oral Echinacea supplementation . J Strength Cond Res. (2012)
  109. Whitehead MT, et al The effect of 4 wk of oral echinacea supplementation on serum erythropoietin and indices of erythropoietic status . Int J Sport Nutr Exerc Metab. (2007)
  110. Szołomicki J, et al The influence of active components of Eleutherococcus senticosus on cellular defence and physical fitness in man . Phytother Res. (2000)
  111. Di Carlo G, et al Effect on prolactin secretion of Echinacea purpurea, hypericum perforatum and Eleutherococcus senticosus . Phytomedicine. (2005)
  112. Dragland S, et al Several culinary and medicinal herbs are important sources of dietary antioxidants . J Nutr. (2003)
  113. Free-radical scavenging capacity and antioxidant activity of selected plant species from the Canadian prairies
  114. Antioxidant Activity and Total Phenolics in Selected Fruits, Vegetables, and Grain Products
  115. Antioxidant activity of extracts of phenolic compounds from selected plant species
  116. Screening of radical scavenging activity of some medicinal and aromatic plant extracts
  117. Antioxidant activity of cichoric acid and alkamides from Echinacea purpurea, alone and in combination
  118. Sharma M, Schoop R, Hudson JB The efficacy of Echinacea in a 3-D tissue model of human airway epithelium . Phytother Res. (2010)
  119. Goel V, et al Echinacea stimulates macrophage function in the lung and spleen of normal rats . J Nutr Biochem. (2002)
  120. Fusco D, et al Echinacea purpurea aerial extract alters course of influenza infection in mice . Vaccine. (2010)
  121. Bodinet C, et al Effect of oral application of an immunomodulating plant extract on Influenza virus type A infection in mice . Planta Med. (2002)
  122. Uluışık D, Keskin E Effects of ginseng and echinacea on cytokine mRNA expression in rats . ScientificWorldJournal. (2012)
  123. Yamada K, et al A comparison of the immunostimulatory effects of the medicinal herbs Echinacea, Ashwagandha and Brahmi . J Ethnopharmacol. (2011)
  124. Spasov AA, et al Comparative controlled study of Andrographis paniculata fixed combination, Kan Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated respiratory disease in children . Phytother Res. (2004)
  125. Posadzki P, Watson LK, Ernst E Adverse effects of herbal medicines: an overview of systematic reviews . Clin Med. (2013)
  126. Huntley AL, Thompson Coon J, Ernst E The safety of herbal medicinal products derived from Echinacea species: a systematic review . Drug Saf. (2005)
  127. Askeroglu U, Alleyne B, Guyuron B Pharmaceutical and herbal products that may contribute to dry eyes . Plast Reconstr Surg. (2013)
  128. [No authors listed Don't take echinacea if you're allergic to ragweed . Consum Rep. (2012)
  129. Mullins RJ Echinacea-associated anaphylaxis . Med J Aust. (1998)
  130. Mullins RJ, Heddle R Adverse reactions associated with echinacea: the Australian experience . Ann Allergy Asthma Immunol. (2002)
  131. Tiralongo E, et al Randomised, double blind, placebo-controlled trial of echinacea supplementation in air travellers . Evid Based Complement Alternat Med. (2012)
  132. Barrett B, et al Echinacea for treating the common cold: a randomized trial . Ann Intern Med. (2010)
  133. O'Neil J, et al Effects of echinacea on the frequency of upper respiratory tract symptoms: a randomized, double-blind, placebo-controlled trial . Ann Allergy Asthma Immunol. (2008)

(Common misspellings for Echinacea include ekinasha, echinashea, ekinacea, echinaceae, echinaisha, eckinacea, eckinaceae)