Natural Foods Merchandiser

Recent Evidence About Echinacea: Is Its Popularity Justified?

Echinacea has long been a popular and widely recommended herb. It is one of the few herbs with almost universal consumer recognition. However, due to a history of mixed clinical results, the debate continues about whether echinacea actually improves immune function or affects the course of mild infections. Although only a handful of clinical trials have been conducted since the 1990s, researchers do continue to assess the actions and effects of echinacea extracts. With echinacea still on consumers' radar screens, retailers should keep up with the research. Following are summaries of some of the more consequential research published in 2002.

Echinacea—whose common name is coneflower or purple coneflower—includes several species used medicinally. Echinacea angustifolia, E. purpurea and E. pallida are harvested for use in echinacea extracts. E. angustifolia and E. pallida roots and E. purpurea and E. pallida flower heads are used for their concentration of certain physiologically active constituents. Several different constituents, such as caffeic acid glycosides (echinosides), alkyl amides (isobutyl amides), cichoric acid, polyenes, flavonoids and essential oils have demonstrable immunomodulatory effects in vitro. Researchers further examined the actions of these constituents and found that the different standardization of these constituent groups in various echinacea extracts may be responsible for the conflicting clinical results.

Animal Studies
In vitro and in vivo studies suggest mechanisms of action and possible clinical effects; however, results from this kind of research do not always bear out in human trials or clinical usage. Consider the following studies:

  • Goel V, et al. "Echinacea stimulates macrophage function in the lung and spleen of normal rats." J Nutr Biochem 2002;13:487-92.

    This is the first study to demonstrate a dose-related immunostimulatory effect of an echinacea extract resulting directly from three standardized constituent groups. Researchers administered four different types of echinacea extracts to healthy, mature rats for four days to determine the effects of specified constituents on the animals' immune function. All the extracts, produced by Natural Factors (Burnaby, British Columbia, Canada) were water-ethanol extractions from the roots or aerial parts of E. purpurea. The phagocytic activity of the macrophages and their production of both nitric oxide and tumor necrosis factor-alpha were affected by the echinacea extract. Nitric oxide production was statistically significant only for the highest concentration extracts. The significance of this finding is that the variable clinical results obtained with echinacea extracts may be the result of variable concentrations of cihoric acid, polysaccharides and alkylamides. Thus, echinacea products standardized to these constituents may be more likely to reliably produce immunostimulatory effects. Although these findings are promising, the same group of researchers found previously, using a similar design with the same type of rats, that only alkylamides elicited significant nitric oxide and TNF-alpha responses.

  • Currier N, Miller S. "The effect of immunization with killed tumor cells, with/without feeding of Echinacea purpurea in an erythroleukemic mouse model." J Alt Comp Med 2002;8(1):49-58.

    Researchers examined the role of powdered E. purpurea extract (Phyto Adrien Gagnon, Sante Naturelle [A.G.] Ltee, La Prairie, Quebec, Canada) in stimulating natural killer cells in young mice receiving an erythroleukemic killed-cell vaccine prior to injection of viable erythroleukemic cells. They wanted to know whether an E. purpurea extract would increase, or sensitize, the anti-tumor response of immune cells (NK cells) after being exposed to the vaccine. After nine days, NK cell populations in echinacea-fed mice were markedly reduced compared with those not fed echinacea and vaccinated. However, this trend was reversed on a subsequent three-month measurement. After three months, survival of the mice given the E. purpurea extract with the vaccine was almost twice that of the mice that received the vaccine only. Specifically, the E. purpurea-fed mice demonstrated significant elevations of NK cells. This may have been the result of E. purpurea stimulating monocytes (macrophage precursor cells) to produce cytokines such as TNF-alpha, which, in turn, stimulate NK cells.

Clinical Trials
Clinical trials comprise the research most relevant for retailers and consumers. This research, when properly designed and controlled, can indicate whether an effect previously observed in vitro or in vivo translates to a demonstrable effect in humans. As these summaries show, the positive results from laboratory studies are not nearly as clearly demonstrated in human trials.

  • Barrett B, et al. "Treatment of the common cold with unrefined echinacea." Ann Intern Med 2002;137(12):939-46.

    Researchers conducted this randomized, double-blind, placebo-controlled community-based trial to determine the efficacy of dried, encapsulated whole-plant echinacea as an early treatment for the common cold. Participants were 148 undergraduate students from the University of Wisconsin; all were at least 18 years old and reported experiencing cold symptoms for no more than 36 hours, were not taking any other treatment for their symptoms, were not pregnant and did not have specified chronic diseases. Participants were assigned to take either placebo (alfalfa capsules) or echinacea capsules. The echinacea capsules were provided by Shaklee Technica and provided a dried mixture of 50 percent E. angustifolia root (123 mg), 25 percent E. purpurea root (62 mg) and 25 percent E. purpurea herb (62 mg). Test capsules also contained thyme (49 mg) and peppermint (31 mg) to disguise the taste and flavor. Several months after the study began, the echinacea capsules were independently assayed by two different labs and found, respectively, to contain 0.20­0.26 percent echinoside, 0.77­0.84 percent cichoric acid and 0.82 percent alkamides. Additionally, the daily equivalent doses were determined to be active via in vitro analysis of macrophage activation and TNF elevation. The study participants took four capsules (1 g of echinacea) six times during the first 24 hours of the study and then took four capsules three times daily thereafter until symptoms resolved, or a maximum of 10 days. The results failed to show a difference in cold duration between the echinacea and placebo groups. The mean duration of cold symptoms was 5.75 days in the placebo group and 6.27 days in the echinacea group (not statistically significant). There was no significant difference in symptom severity or adverse events between the echinacea and the placebo groups.

    The study's authors pointed out several limitations to this trial. They said the preparation used had not been previously tested—it wasn't an extract, but rather a whole-plant concentrate—and may be ineffective because of bioavailability issues or the array and proportion of phytoconstituents. Additionally, the authors surmise the study population of healthy undergraduate students may not, as a group, gain much benefit from echinacea. Instead, they suggest echinacea may have greater benefit for the immunocompromised. Finally, this trial was designed to detect a reduction in symptom severity of at least 22 percent; the authors said an effect size of 5 percent or 10 percent could have occurred, but been missed given the size of the trial. In addition to these qualifications, Ronald B. Turner, M.D., says in an editorial in the same issue that enhancing host immune response presumably caused by echinacea may, in fact, worsen the symptoms of a viral respiratory infection. This postulation is based on the emerging evidence that symptoms of viral infections are mediated, in part, by host inflammatory responses.

  • Kim L, et al. "Immunological activity of larch arabinogalactan and echinacea: a preliminary, randomized, double-blind, placebo-controlled trial." Altern Med Rev 2002;7(2):138-49.

    This preliminary study was designed to explore the immunomodulating effects of E. purpurea, E. angustifolia and larch arabinogalactan from Larix occidentalis. Researchers recruited 48 healthy females aged 22 to 51 years. The women were without major illness or acute illness and weren't taking immune-enhancing supplements or medications. Subjects were randomly assigned to one of six groups:

    • E. purpurea whole herb extract (4 percent phenols, 1.5 g/day)

    • E. purpurea whole herb extract (4 percent phenols, 780 mg/day), and ultra-refined E. purpurea whole herb with E. angustifolia root (680 mg/day)

    • E. purpurea whole herb extract (4 percent phenols, 908 mg/day), E. purpurea whole herb (464 mg/day) and E. angustifolia root (36 mg/day)

    • E. purpurea whole herb extract (4 percent phenols, 908 mg/day), E. purpurea whole herb (464 mg/day), E. angustifolia root (36 mg/day) and larch arabinogalactan (90 percent, 1.5 g/day)

    • Larch arabinogalactan (90 percent, 1.5 g/day)

    • Placebo (alfalfa and rice flour; 1.5 g/day>

All capsules were visually indistinguishable. Subjects reported they were compliant for the four-week study. Results demonstrated that the concentration of complement properdin, a marker of immune function, increased in the serum of the subjects in group three by 21 percent (p<0.05) and group four by 18 percent (p<0.05), but these increases were not statistically significant.

No significant changes occurred in the other lab parameters studied. However, TNF-alpha did show a nonsignificant decrease in each of the groups, including placebo, compared with baseline values. Subjects in groups three and four rated their quality of life as enhanced compared with baseline ratings. Additionally, symptom scores related to gastrointestinal function, sleep and mood displayed significant increases, relative to baseline, in these same two groups.

The increase in complement properdin may indicate complement immune system stimulation; however, the authors say the large variance in the baseline values between groups limits interpretation of these results. The authors also note this study failed to demonstrate statistically significant activities of echinacea and larch arabinogalactan, which could be the result of the methodology used. Alternatively, the echinacea combinations used may be without biological effect. The authors said further study is warranted because this research had small sample sizes in each group, didn't measure other markers of immunity and lacked rigor in design and statistical methods.

  • Schwarz E, et al. "Oral administration of freshly expressed juice of Echinacea purpurea herbs fail to stimulate the nonspecific immune response in healthy young men: results of a double-blind, placebo-controlled crossover study." J Immunother 2002 Sep-Oct;25(5):413-20.

    Forty healthy male volunteers between the ages of 20 and 40 participated in this study to determine whether phagocytic activity and cytokine production are stimulated by oral doses of a commercially available echinacea preparation (Esberitox). The men received either a freshly expressed juice of E. purpurea herbs or placebo juice using a double-blind, placebo-controlled crossover design. The trial had two treatment periods of 14 days and a washout period of four weeks in between.

    To evaluate immune stimulation, researchers measured phagocytic activity of polymorphonuclear leukocytes and monocytes, and production of TNF-alpha and interleukin (IL)-1beta. The herb did not enhance phagocytic activity of polymorphonuclear leukocytes or monocytes compared with placebo. Echinacea did not influence the production TNF-alpha or IL-1beta by LPS-stimulated monocytes. "The 'immune stimulation' by Echinacea purpurea observed in vitro and after parenteral administration are not confirmed in healthy humans after oral intake," according to these researchers.

What Does It All Mean?
These most recent clinical trials of echinacea preparations paint a hazy picture. Encapsulated echinacea products create immunological changes; however, associated changes in clinical symptomatology are harder to detect. This is, in fact, consistent with the results of previous echinacea trials. The clinical effects are likely to be small, especially in young and healthy individuals. When changes in clinical outcomes are observed, the changes are typically subtle and may not be significant to the individual taking the supplement.

On the other hand, echinacea, or at least injectable polysaccharides from E. purpurea, may result in clinically relevant immune system changes in severely immunocompromised individuals, notably those receiving myelosuppressive chemotherapy.

Lise Alschuler, N.D., is the director of the naturopathic medicine department at Midwestern Regional Medical Center, Cancer Treatment Centers of America in Zion, Ill. Alschuler has no professional or financial affiliations with any manufacturer or distributor of echinacea products.

Natural Foods Merchandiser volume XXIV/number 7/p. 36, 38

Alternative Applications

Echinacea isn't just for the cold season. Researchers are testing its mettle against herpes and inflammation.

  • Binns S, et al. "Antiviral activity of characterized extracts from Echinacea spp. (Heliantheae: Asteraceae) against Herpes simplex virus (HSV-1)." Planta Med 2002;68:780-3.

    In this in vitro study, researchers evaluated the antiviral activity of eight different 70 percent ethanolic extracts of echinacea against Herpes simplex virus Type I. Overall, the most potent inhibitors of HSV type 1 were E. pallida var. sanguinea 70 percent ethanol (minimum inhibitory concentration=0.026mg/mL), cichoric acid (MIC=0.045mg/mL) and E. purpurea n-hexane root extract (MIC= 0.12mg/mL). MIC is the minimum concentration of the antibacterial agent required to inhibit growth. The authors of this study conclude from their analysis of all the extracts that higher antiviral activities may be the result of caffeic acid derivatives, namely cichoric acid.

  • Clifford L, et al. "Bioactivity of alkamides isolated from Echinacea purpurea (L.) Moench." Phytomedicine 2002;9:249-53.

    Researchers examined the anti-inflammatory effects of purified alkamides (various forms of isobutylamides) isolated from the dried root of E. purpurea. The results demonstrated 36 percent to 60 percent COX-1 and 15 percent to 46 percent COX-2 inhibition from individual alkamides. This indicates that echinacea extracts may create a nonspecific anti-inflammatory effect.

Natural Foods Merchandiser volume XXIV/number 7/p. 36

Echinacea Safety

Echinacea extracts appear to be safe, even in pregnant women, but people with genetic predispositions to allergic reactions should exercise caution.

  • Gallo M, et al. "Pregnancy outcome following gestational exposure to echinacea." Arch Intern Med 2002;160:3141-3.

    This prospective controlled study involved 206 women who used echinacea products during pregnancy. Of the enrolled women, 54 percent used echinacea in the first trimester and 8 percent were exposed to echinacea in all three trimesters. Of the echinacea users, 58 percent used capsules or tablets with doses ranging from 250 to 1,000 mg daily; 38 percent used tinctures (alcohol content between 25 percent and 45 percent) with doses ranging from five to 30 drops daily for five to seven days.

    A disease-matched control group of 206 women demonstrated no statistical difference in terms of pregnancy or birth outcomes. The authors of this study conclude that gestational use of echinacea during embryonic development is not associated with a detectable increased risk for major fetal malformations.

  • Mullins R, Heddle R: "Adverse reactions associated with echinacea: the Australia experience." Ann Allergy Asthma Immunol 2002;88:42-51.

    In this report of five patients with adverse reactions to echinacea, two suffered anaphylaxis, one suffered an acute asthma attack 10 minutes after the first dose, another suffered recurrent episodes of mild asthma with each dose and the fifth patient developed a maculopapular rash within two days after each echinacea dose. Three of these five patients had positive skin-prick testing to echinacea. In reviewing 51 other adverse drug reports involving echinacea, the authors found that atopic individuals are over-represented in those experiencing reactions to echinacea. Furthermore, this data supports the possibility that cross-reactivity between echinacea and environmental allergens may trigger an allergic reaction to first-time echinacea users. The authors conclude that atopic individuals should be cautioned appropriately before using echinacea.

Natural Foods Merchandiser volume XXIV/number 7/p. 38

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